@article {pmid41453578,
year = {2025},
author = {Ishikawa, R and Yamazaki, Y and Nakazawa, N and Li, X and Tazuma, T and Takebayashi, Y and Nakamori, M and Sotomaru, Y and Maruyama, H},
title = {A novel conditional knock-in mouse model for APOE4-to-APOE3 switching.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107244},
doi = {10.1016/j.nbd.2025.107244},
pmid = {41453578},
issn = {1095-953X},
abstract = {APOE polymorphisms are major genetic risk factors of Alzheimer's disease (AD). Compared with APOE3/E3, the APOE4/E4 genotype is associated with a > 14-fold increased risk. Therefore, we hypothesized that conversion of APOE4 to APOE3 would ameliorate AD-related pathologies. Accordingly, we generated a knock-in mouse model harboring an APOE4-FLEx (Flip-Excision) 4-to-3 construct enabling postnatal Cre-mediated APOE4-to-APOE3 switching. This construct comprised an APOE3 exon inserted in a reverse orientation downstream of the APOE4 exon, flanked by alternating loxP and mutant loxP sites, allowing Cre-mediated FLEx switching from APOE4-to-APOE3. For in vitro validation, HEK293T cells were transfected with APOE4-FLEx 4-to-3 plasmid, followed by AAV8-mediated iCre delivery. For in vivo studies, endogenous Apoe was replaced with the APOE4-FLEx 4-to-3 construct to generate APOE4-FLEx 4-to-3 knock-in mice, which were crossed with tamoxifen-inducible Rosa26-CreERT2 mice to yield Cre: APOE4-FLEx 4-to-3 double-knock-in mice. Tamoxifen was administered to induce APOE switching. Cre expression successfully induced APOE4-to-APOE3 switching in vitro. Tamoxifen administration in Cre: APOE4-FLEx 4-to-3 mice triggered APOE4-to-APOE3 switching in the liver, demonstrating the feasibility of postnatal isoform switching. However, brain APOE protein levels were below the detection limit. Investigation of the underlying cause involving transcript analysis revealed aberrant retention of intron 3 (APOE-I3). This abnormal splicing probably contributed to the decreased expression of fully spliced, translation-competent (mature) APOE mRNA, driving the subsequent protein reduction. Although APOE expression across organs in APOE4-FLEx 4-to-3 mice requires further optimization, our findings demonstrate that Cre-mediated FLEx switching can serve as a potential strategy to induce APOE genotype switching in vivo.},
}

@article {pmid41453577,
year = {2025},
author = {Singh, T and Bridgeman, E and Baker, AJ and Noblet, HA and Yang, KY and Kang, S and Lim, KH and Lee, SS and Amundsen, NM and Lee, Y and Selvin, PR and Kong, H and Chung, HJ},
title = {APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107246},
doi = {10.1016/j.nbd.2025.107246},
pmid = {41453577},
issn = {1095-953X},
abstract = {Alzheimer's disease (AD) is the leading cause of dementia, characterized by the deposition of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau. Seizures have also emerged as a prevalent clinical feature of AD and are associated with APOE4, the major genetic risk factor of AD. However, the mechanism by which APOE4 induces seizures and neuronal hyperexcitability is incompletely understood. We discovered that human APOE4 targeted replacement mice showed increased seizure severity and seizure-induced death at 5.5-7 but not 2-3 months of age compared to APOE3 mice using the kainic acid model of status epilepticus which preferentially arises from the hippocampus. While Tau burden alone did not alter seizure susceptibility in mice, APOE4 together with Tau burden enhanced seizure severity in female mice. Notably, APOE4 was associated with decreased hippocampal levels of sodium/potassium-ATPase, ATP-generating glycolytic enzymes, including phosphoglycerate kinase 1 (PGK1) and pyruvate kinase M, and ATP. While inhibition of Na[+]/K[+]- ATPase increased hippocampal neuronal activity, pharmacologically stimulating PGK1 with terazosin increased hippocampal ATP levels and decreased seizure severity in APOE4 but not APOE3 mice. Lastly, co-application of lactate dehydrogenase inhibitor sodium oxamate to prevent the conversion of pyruvate to lactate further enhanced hippocampal ATP levels and suppressed seizure severity in APOE4 mice. Together, these findings suggest that reductions in hippocampal expression of sodium/potassium-ATPase and glycolytic enzymes may underlie APOE4-associated hippocampal hyperexcitability, revealing a novel mechanistic insight. Our results also demonstrate potent anti-seizure effects of terazosin, supporting the possibility of repurposing this anti-hypertension drug to mitigate seizure comorbidity in AD.},
}

@article {pmid41453554,
year = {2025},
author = {Coria-Lucero, C and Lopez, M and Gomez-Mejiba, S and Ramirez, D and Delsouc, MB and Casais, M and Alba, R and Leporatti, J and Delgado, S and Anzulovich, AC and Navigatore-Fonzo, L},
title = {Daily temporal organization of inflammation and cognition-related factors and antioxidant enzymes are modified by an intracerebroventricular injection of amyloid-beta peptide (1-42) aggregates in the rat temporal cortex.},
journal = {Brain research},
volume = {},
number = {},
pages = {150135},
doi = {10.1016/j.brainres.2025.150135},
pmid = {41453554},
issn = {1872-6240},
abstract = {Alzheimer's dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, oxidative damage, neuroinflammation, synaptic loss and neuronal cell death. The accumulation of Aβ in the brain plays a key role in the pathogenesis of AD. Elevated levels of Aβ causes an increase in oxidative damage and neuroinflammation both are considered key factors in the progression of AD. Also patients with Alzheimer's show alterations in their circadian rhythms. Our objectives were (a) to analyze whether inflammation and cognition-related factors exhibit a day-night variation, (b) to verify whether antioxidant enzymes expression and activity exhibit a daily rhythm in the rat temporal cortex and (c) to evaluate the effects of an intracerebroventricular injection of Aβ-amyloid (1-42) aggregates on those temporal profiles. Four-month old males Holtzman rats were used in this study. Groups were defined as: 1) control 2) Aβ-injected. Rats were maintained under 12 h-Light:12 h-Dark conditions with food ad-libitum. Our results showed temporal patterns of nitrites, iNOS, catalase and glutathione peroxidase expression and activity, as well as Rc3 and Gap-43 mRNA, in the rat temporal cortex. An i.c.v. injection of Aβ abolishes the temporal pattern of Rc3 and Gap-43 mRNA. Also increased the rhythm's mesor of NO and iNOS levels, reduced the mesor of CAT activity rhythms, and changed the phase of GPx activity patterns. These alterations in the temporal patterns of inflammation and redox status-related factors would affect cellular clock activity and consequently cognitive performance.},
}

@article {pmid41453542,
year = {2025},
author = {Fu, X and Han, J and Xia, Y and Wang, W and Wen, Y and Zhang, B and Zhang, X and Wang, X and Han, S and Zhang, C},
title = {Eleutheroside B ameliorates AD-like pathological features in Caenorhabditis elegans by inducing autophagy and combating oxidative stress.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2025.12.043},
pmid = {41453542},
issn = {1873-4596},
abstract = {Alzheimer's disease (AD) incidence is rising with no effective treatments. Eleutheroside B (EB) has neuroprotective potential, but its therapeutic effects and mechanisms in AD are unclear. This study investigated EB's effects on AD pathologies and elucidated its underlying mechanisms using a transgenic Caenorhabditis elegans (C. elegans) model. We found that EB could ameliorate cognitive impairment, locomotor dysfunction, and shortened lifespan induced by amyloid-β(Aβ) and Tau aggregation in C. elegans, and reduce the relative expression levels of Aβ, Tau, and phosphorylated Tau (p-Tau) proteins. EB significantly improved the health status and anti-aging capacity of the worms, as evidenced by prolonged healthspan, elevated pharyngeal pumping rate and body bend frequency, and increased body length and width. Notably, EB exhibited no observable toxicity even at high-dose administration. Furthermore, EB activated key antioxidant transcription factors skn-1, daf-16, and hsf-1; it also increased the expression levels of antioxidant enzymes superoxide dismutase-3(SOD-3) and glutathione S-transferase 4(GST-4), decreased reactive oxygen species (ROS) levels, and elevated the expression of heat shock proteins Hsp-4 and Hsp-6. EB also reduced the accumulation of p62/SQST-1 protein, promoted the colocalization of lgg-1::GFP with lysosomes, and increased the relative mRNA expression of autophagy-related genes aak-2, unc-51, bec-1, vps-34, and lgg-1. After targeted knockdown of these genes, the protective effects of EB against AD-related pathologies were abolished. Our findings demonstrate that EB exhibits anti-aging properties and potential for ameliorating AD, which is likely mediated via antioxidative activities and autophagy induction.},
}

@article {pmid41453462,
year = {2025},
author = {Guleria, M and Kamble, A and Upadhyay, M and Sethi, P and Patel, MB and Malhan, A and Rastogi, S and Datta, D and Singh, S and Prajapati, BG},
title = {Lipid-based nanostructures in targeted management of neurological disorders: a comprehensive review.},
journal = {International journal of pharmaceutics},
volume = {},
number = {},
pages = {126530},
doi = {10.1016/j.ijpharm.2025.126530},
pmid = {41453462},
issn = {1873-3476},
abstract = {Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and brain tumors remain major global health burdens due to complex pathology and the restrictive nature of CNS barriers, including the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Non-invasive nose-to-brain delivery has emerged as a promising strategy to bypass these barriers and lipid-based nanostructures such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions, liposomes and vesicular systems are gaining prominence for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic therapeutics. This review summarizes the advancements in targeted lyophilised lipid-based nanocarriers for central nervous system (CNS) drug delivery, covering anatomical barriers, nose-to-brain transport mechanisms, formulation strategies and solidification techniques like freeze-drying and spray-drying that improve stability and usability. Key findings indicate that lyophilisation enhances structural integrity, long-term storage and reconstitution without loss of efficacy. Comparative advantages include improved mucoadhesion, protection from enzymatic degradation, sustained and stimuli-responsive release, and better patient compliance, further strengthened by surface modifications that enhance targeting efficiency. The review highlights recent clinical progress and patent developments, emphasizing the translational potential of these systems. It also addresses major challenges, including scale-up barriers, lipid polymorphism, cryoprotectant optimization, aggregation risks, long-term safety concerns and regulatory hurdles. Overall, lyophilised lipid-based nanostructures offer a versatile and promising platform for CNS therapeutics. Future perspectives focus on overcoming existing limitations and developing next-generation hybrid, stimuli-responsive and precision-targeted systems to advance effective neurological drug delivery.},
}

@article {pmid41453420,
year = {2025},
author = {Bender, AR and Giriprakash, PP and Yang, Z and Cordes, D and Caldwell, JZ},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104522},
doi = {10.1002/alz70856_104522},
pmid = {41453420},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; Biomarkers/metabolism ; *Cognitive Dysfunction/diagnostic imaging/pathology/metabolism ; *Amyloid beta-Peptides/metabolism ; Diffusion Magnetic Resonance Imaging ; Positron-Emission Tomography ; Neuropsychological Tests ; *Brain/diagnostic imaging/pathology ; *Alzheimer Disease/diagnostic imaging ; *White Matter/diagnostic imaging/pathology ; Aged, 80 and over ; Middle Aged ; },
abstract = {BACKGROUND: Alzheimer's disease is associated with altered brain microstructure, measurable via diffusion-weighted magnetic resonance imaging (dMRI). Extant findings suggest later-developing, smaller-caliber axons are particularly vulnerable to early-stage Alzheimer's neuropathologies; we hypothesized such changes are observable via dMRI measures of fiber density (FD) and dispersion. We investigated whether elevated amyloid-β (Aβ) predicts differences in FD and fiber dispersion in older adults without dementia, and the sensitivity of Aβ-associated microstructural parameters to cognitive function.

METHOD: Data from 122 participants (45% F; 7.4% NHW) enrolled in the Center for Neurodegeneration and Translational Neuroscience included those characterized as cognitively unimpaired (n = 58) or consensus diagnosed with amnestic mild cognitive impairment (n = 64). Participants underwent multi-shell dMRI and amyloid PET neuroimaging; all completed standardized neuropsychological tests of visual reproduction, executive function, working memory, and semantic fluency. We calculated standardized uptake value ratio from PET data, rescaled to centiloids. DMRI processing leveraged MRtrix3 to model total FD and fiber dispersion as voxelwise scalars. Separate mass-univariate voxel-based analyses assessed total centiloid level predicting differences in total FD and dispersion, while accounting for age, sex, handedness, and head size; all results are nonparametrically corrected for familywise error rate.

RESULT: Higher Aβ predicted widely reduced fiber dispersion in transcallosal regions, anterior cingulum bundle, superior longitudinal fasciculi, and left anterior hippocampus, but predicted increased dispersion in cerebellar hemispheres (Figure 1). Post hoc regressions of mean fiber dispersion in Aβ-negative voxels showed remarkably strong associations with centiloid level (r = -0.78, p <.001, adjusted-R[2] = 0.64). In contrast, Aβ positively predicted FD in striatal, thalamic, midbrain, and cerebellar projection fibers, and in corpus callosum-genu (r = 0.34, p <.001). Regressions of cognitive performance showed mean fiber dispersion significantly predicted CDR sum-of-boxes, delayed recall, verbal fluency, working memory, and executive function (Figure 2), controlling for age, sex, and education; associations between FD and behavior were attenuated by age and sex.

CONCLUSION: Aβ neuropathology is associated with altered white matter organization in community-dwelling adults without dementia. Fiber dispersion is a novel dMRI measure with exceptional correspondence to Aβ-PET centiloid levels and cognition, independent of age and sex. Modeling fiber density and dispersion afford complementary insights about microstructural changes associated with Alzheimer's pathology and cognitive function.},
}

Humans
Male
Female
Aged
Biomarkers/metabolism
*Cognitive Dysfunction/diagnostic imaging/pathology/metabolism
*Amyloid beta-Peptides/metabolism
Diffusion Magnetic Resonance Imaging
Positron-Emission Tomography
Neuropsychological Tests
*Brain/diagnostic imaging/pathology
*Alzheimer Disease/diagnostic imaging
*White Matter/diagnostic imaging/pathology
Aged, 80 and over
Middle Aged

@article {pmid41453418,
year = {2025},
author = {Summanwar, D and Willis, DR and Fowler, NR},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107569},
doi = {10.1002/alz70858_107569},
pmid = {41453418},
issn = {1552-5279},
mesh = {Humans ; *Primary Health Care ; Male ; Female ; *Dementia/psychology/diagnosis/therapy ; Aged ; *Cognitive Dysfunction/diagnosis/psychology/therapy ; Aged, 80 and over ; },
abstract = {BACKGROUND: Primary Care Providers (PCPs) are often the first point of contact for older adults with mild cognitive impairment (MCI) and Alzheimer's disease and related dementias (ADRD). However, resource and time constraints hinder the ability of primary care practices to perform early detection and timely intervention. To address this gap, scalable models are needed to identify individuals at risk for MCI and ADRD, notify them of their elevated risk, and engage them in care pathways for evaluation, treatment, and research participation.

METHOD: Using a user-center design approach, we engaged primary care patients in co-developing a messaging strategy aimed at effectively reaching individuals at elevated risk for cognitive impairment, assessing whether they experience any subjective cognitive concerns, and gauging their interest in connecting to a clinical Brain Health Navigator for further evaluation and support.

RESULT: We enrolled a diverse cohort of 16 primary care patients in a user-centered design session, during which key themes emerged as essential willingness to engage with the outreach messaging. Patients emphasized the importance of recognizable connection to their PCP, such as including their PCP's name in the initial message. They also preferred timely outreach, ideally aligned with upcoming primary care appointments, to enhance relevance and engagement. In addition, clarity about why they were being contacted regarding brain health and how a brain health navigator could support their care journey was critical to fostering trust and willingness to pursue next steps. Based on these insights, draft messages were developed.

CONCLUSION: Applying user-centered design techniques to brain health messaging helps identify key patient engagement factors necessary for the development of scalable, technology-driven outreach strategies. This approach enhances early detection efforts in primary care patients and supports timely evaluation and intervention.},
}

Humans
*Primary Health Care
Male
Female
*Dementia/psychology/diagnosis/therapy
Aged
*Cognitive Dysfunction/diagnosis/psychology/therapy
Aged, 80 and over

@article {pmid41453397,
year = {2025},
author = {Dixon, RA and Drouin, SM and Bohn, L and Zhao, S and Li, L},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104500},
doi = {10.1002/alz70856_104500},
pmid = {41453397},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/metabolism/blood ; *Alzheimer Disease/diagnosis/metabolism ; Male ; Female ; *Cognitive Dysfunction/metabolism/diagnosis ; Aged ; Machine Learning ; Metabolomics ; Cohort Studies ; Saliva/metabolism/chemistry ; Risk Factors ; Aged, 80 and over ; Canada ; },
abstract = {BACKGROUND: Recent research approaches to an expanding collection of well-characterized databases have examined varying arrays of biomarkers and risk factors related to Alzheimer's disease (AD). Analytical techniques that simultaneously evaluate relative importance of numerous candidate factors can successfully identify leading predictors within multiple-variable, high-dimensional datasets. Our objective was to integrate new molecular biomarkers with established AD-related biomarkers and risk factors to evaluate their relative predictive contributions using a series of machine learning classifier models.

METHOD: We assembled 92 AD-related indicators representing 10 key modalities of AD risk (demographic, biomarkers, lifestyle, sensory, vascular, imaging, functional, psychiatric, anthropometric, clinical health) for participants from three cohorts in the Canadian Consortium on Neurodegeneration in Aging database (aka COMPASS-ND): (1) Cognitively Unimpaired (CU), (2) Mild Cognitive Impairment (MCI), (3) AD. Each cohort was divided for separate 3-group training and validation analyses. Novelty: High-throughput metabolomics analyses were conducted on both serum and saliva, each analysis detecting over 7000 metabolite peaks. Leading molecular predictors for the two-group comparisons and two AD-related bile acids produced 20 novel predictors. Data-driven analyses (in Python 3.9) included three machine learning classifier algorithms (eg, sklearn RandomForestClassifier) processing 112 (92+20) predictors.

RESULT: Three sets of analyses (same predictors) were conducted (Predicting AD (CU-AD); Predicting MCI (CU-MCI); Predicting dementia (MCI-AD)). All models performed successfully in the main metrics (eg, Accuracy, Precision; AUC range: 0.81 - 0.98). Key results displayed in Explainable AI Tree SHAP plots vividly depicted discriminating patterns of leading multi-modal predictors. Commonly observed predictors were from new metabolomics analyses (saliva, blood), imaging, vascular, AD biomarkers, sensory, clinical health and lifestyle. Figure 1 displays the overall models tested (left panel) and the results for Predicting Dementia (right panel). A striking result is that of 112 predictors, the top 20 included 8 newly discovered metabolites, 5 of which were from salivary analyses.

CONCLUSION: New molecular biomarkers (from both blood and saliva) perform strongly when integrated into databases with established AD biomarkers and risk factors. Implications include (1) enhancing identification of early mechanistic pathways, (2) importance of conducting integrative and interactive biomarker analyses, especially data-driven, and (3) potential for non-invasive salivary biomarkers for promoting assessment accessibility across diverse communities.},
}

Humans
*Biomarkers/metabolism/blood
*Alzheimer Disease/diagnosis/metabolism
Male
Female
*Cognitive Dysfunction/metabolism/diagnosis
Aged
Machine Learning
Metabolomics
Cohort Studies
Saliva/metabolism/chemistry
Risk Factors
Aged, 80 and over
Canada

@article {pmid41453367,
year = {2025},
author = {Souza-Talarico, JN and Capuano, AW and Barnes, LL},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107802},
doi = {10.1002/alz70858_107802},
pmid = {41453367},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; *Black or African American/psychology ; *Dementia/psychology/ethnology ; Longitudinal Studies ; Biomarkers/blood ; *Cognitive Dysfunction/psychology ; Aged, 80 and over ; White ; },
abstract = {BACKGROUND: Black Americans are twice as likely to develop Alzheimer's Disease and Related Dementias (ADRD) compared to White individuals, with psychological and social factors contributing to this disparity. The biological mechanisms linking these factors to cognitive decline are still under investigation. A multi-domain approach across individual, interpersonal, and community levels is necessary to understand this complex relationship. This study aimed to determine the associations between psychological, environmental, and biological factors linked to cognitive decline in older Black adults.

METHODS: Longitudinal data from 118 Black Americans aged 65 and older from the Minority Aging Research Study (MARS) were analyzed. The biological factors at the individual level included blood-based neuroendocrine (cortisol, DHEA-S, testosterone, IGF-1), immunologic (IL-10, IL-1ra, IL-6, CRP, TNF-α), and metabolic (LDL-C, HbA1C, BMI, GFR) markers. Discrimination, a psychological factor at the interpersonal level, was measured using the Everyday Discrimination Scale (EDS). The Social Vulnerability Index, a geospatial data comprising socioeconomic, housing and transportation, minority groups and language, and household and disability, assessed the environmental factors at the community level. Cognitive decline, the primary outcome, was evaluated using annual performance on global cognition, processing speed, working, semantic, and episodic memory tests since 2004. Ordinal models and a stepwise approach identified markers associated with discrimination, social vulnerability, and cognition.

RESULTS: Controlling for sex, age, and education, high EDS was associated with neuroendocrine (cortisol p = .007; IGF-1 p = .026; testosterone p = .009) and immunological markers (IL-1ra p = .006; TNF-α p = .044), while high SVI was linked to neuroendocrine (cortisol p = .0010; IGF1 p = .018), and metabolic markers (LDL p = .005, BMI p = .044). In the final models, EDS (p = .039), SVI (p = .019), neuroendocrine (IGF1 p = .029, DHEAS p = .022), immunological (CRP p = .016; IL-1ra p = .05; TNF-α (p = .030) and metabolic (HbA1C p = .018 BMI p = .03, glucose p = .038, GRF1 p = .029) markers were associated with decline in global cognition, working memory processing speed and semantic memory.

CONCLUSION: These findings suggest that psychological, environmental, and biological factors at the individual, interpersonal, and community levels may synergistically contribute to cognitive decline. Our findings inform future research incorporating ADRD biomarkers to improve early prediction of ADRD and enable timely prevention through precise medicine.},
}

Humans
Male
Female
Aged
*Black or African American/psychology
*Dementia/psychology/ethnology
Longitudinal Studies
Biomarkers/blood
*Cognitive Dysfunction/psychology
Aged, 80 and over
White

@article {pmid41453364,
year = {2025},
author = {Babatope, EY and Ramírez-Acosta, AÁ and García-Vázquez, MS},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107189},
doi = {10.1002/alz70858_107189},
pmid = {41453364},
issn = {1552-5279},
mesh = {Humans ; *Dementia/diagnosis/psychology/therapy ; Artificial Intelligence ; *Alzheimer Disease/diagnosis/psychology/therapy ; Latin America ; Wearable Electronic Devices ; Caregivers/psychology ; },
abstract = {BACKGROUND: Globally, technology is a powerful transformative tool, with undeniable innovations and record-breaking potential in almost every sector. Advancement in technology has paved the way for improvement in Alzheimer's disease (AD) and other types of dementia. Technologies including artificial intelligence driven approaches, wearable devices, smart home technologies, computerized batteries are used for health monitoring and diagnosis. In Latin American countries, the growing research effort is evident in the annual satellite symposium organized by the Alzheimer's association. This review evaluates various existing technological tools that are used in the Latin American countries for the diagnosis of Alzheimer's disease.

METHOD: We conducted a rigorous search of data repositories such as web of science, Scopus, PubMed, science direct and Wiley online library to identify papers related to the use of technology in AD diagnosis within this region. Keywords such as assistive technology, smart home technology, artificial intelligence, Alzheimer's disease, dementia, diagnosis, monitoring, and support, were used. The selected paper will be analyzed, and the findings discussed.

RESULT: Evidence from the selected articles will be summarized and presented to emphasize the role of these technological tools in Alzheimer's diagnosis within the Latin American countries. The challenges identified by the authors of these papers will be discussed.

CONCLUSION: Although these technologies offer promising solutions, the challenges associated with their use in these Latin American countries will be discussed to bridge the gap and provide solutions to overcome these challenges. This review evaluates various existing technologies with the intention to interdisciplinary collaboration between end users (the clinicians providing care, the people living with the disease, caregivers and family members) and technology experts to optimize its impact.},
}

Humans
*Dementia/diagnosis/psychology/therapy
Artificial Intelligence
*Alzheimer Disease/diagnosis/psychology/therapy
Latin America
Wearable Electronic Devices
Caregivers/psychology

@article {pmid41453361,
year = {2025},
author = {Evans, K},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e110738},
doi = {10.1002/alz70858_110738},
pmid = {41453361},
issn = {1552-5279},
mesh = {Humans ; *Dementia/therapy/psychology ; },
abstract = {This session will provide an introduction to dementia care coordination and navigation, including the Alzheimer's Association's role in these initiatives. Additionally, an overview of the GUIDE Model, including the program's associated goals and potential impact on dementia care will be discussed.},
}

Humans
*Dementia/therapy/psychology

@article {pmid41453352,
year = {2025},
author = {Hodgson, NA},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e110765},
doi = {10.1002/alz70858_110765},
pmid = {41453352},
issn = {1552-5279},
mesh = {Humans ; *Dementia/therapy/psychology ; *Caregivers/psychology ; Female ; Male ; Aged ; Telephone ; Middle Aged ; },
abstract = {Dementia Care Coordination (DCC) represents a novel telephone-based care coordination service that bridges the gap between clinical care and community support by training healthcare providers to systematically identify dementia caregivers and refer them to trained Alzheimer's Association care consultants who provide personalized education, resources, and ongoing support. This innovative model addresses critical care coordination gaps in dementia care delivery. Caregivers demonstrated maintained or improved self-efficacy scores following DCC participation. Despite experiencing common barriers including caregiver burden and time constraints, participants showed exceptionally high engagement: 70% action plan uptake, 80% resource utilization, and 90% action plan comprehension. Health system employees reported high program satisfaction, though clinician engagement barriers were identified. The DCC model demonstrates promising effectiveness in coordinating dementia care across multiple geographic regions and diverse health system contexts. This multi-state implementation demonstrates the feasibility and promise of innovative telephone-based dementia care coordination. The rigorous implementation science evaluation identified key success factors and improvement opportunities, providing evidence-based guidance for program refinement, sustainability planning, and strategic expansion to additional healthcare systems and regions.},
}

Humans
*Dementia/therapy/psychology
*Caregivers/psychology
Female
Male
Aged
Telephone
Middle Aged

@article {pmid41453299,
year = {2025},
author = {Lee, H and Seo, EH and Yang, HS and Song, YE and Kim, N and Kim, H and Kang, Y and Kim, K and Jeong, Y and Jun, GR and Choi, YB and Lee, KH and , },
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106748},
doi = {10.1002/alz70858_106748},
pmid = {41453299},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Aged ; Pilot Projects ; Risk Factors ; *Asian/psychology ; *Cognitive Dysfunction/psychology/diagnosis/ethnology ; Middle Aged ; *Dementia/psychology/diagnosis/ethnology ; Neuropsychological Tests ; Cohort Studies ; Aged, 80 and over ; },
abstract = {BACKGROUND: Alzheimer's disease and related dementia (ADRD) is rapidly increasing among the Asian American population. Studies have shown that risk factors for ADRD are not uniform across the population, and vary significantly depending on factors including ethnicity, socio-environment, and individual clinical presentation. More research is needed to address the unique challenges faced by Asian Americans, including identifying specific risk factors within this diverse population. The purpose of this paper is to provide group-specific risk factors for ADRD among Korean American older adult groups.

METHODS: A pilot cohort study of 54 Korean American adults ≥60 years old completed cognitive, socio-cultural, functional, and neurological assessments to make a diagnosis of normal control (NC), subjective cognitive complaints (SCC), mild cognitive impairment (MCI), or dementia (DEM). Selected risk factors were compared between groups (NC-SCC vs. MCI-DEM) by either a t-test or a Chi-squared test.

RESULTS: As a part of the Asian Cohort for Alzheimer's Disease pilot study, 54 participants, 67% were females, the mean age of all the participants was 70.1 ( ± 7.2) years, ranging from 60 to 101, and 17% had completed elementary school education. Thirty-three (33) were diagnosed as NC-SCC while 21 were diagnosed with MCI-DEM. Compared with the NC-SCC group, the MCI-DEM group showed a significant decline in cognitive performance (p < .001) measured by the modified mini-mental status examination, common objective test, fluency test, and clock drawing test. The NC-SCC group had better functional activities of daily living (p < .001) compared to the MCI-DEM group. The MCI-DEM group was older (p = .003) and had higher depression levels than the NC-SCC group (p = .001). However, no significant difference was observed with other factors for ADRD including gender, education, length of stay in the U.S., English proficiency, hypertension, diabetes, and high cholesterol.

CONCLUSIONS: The study demonstrates that the MIC-DEM group experienced a significant cognitive decline compared to the NC-SCC group and that age and depression, are significantly elevated in the MCI-DEM group compared to the NC-SCC group. Future research should replicate and expand upon our findings to enhance understanding of group specific-risk factors and cognitive profiles in dementia staging to improve the early detection of ADRD.},
}

Humans
Female
Male
Aged
Pilot Projects
Risk Factors
*Asian/psychology
*Cognitive Dysfunction/psychology/diagnosis/ethnology
Middle Aged
*Dementia/psychology/diagnosis/ethnology
Neuropsychological Tests
Cohort Studies
Aged, 80 and over

@article {pmid41453230,
year = {2025},
author = {Dhana, K and Arfanakis, K and Aggarwal, NT and Sacks, F and Barnes, LL},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104001},
doi = {10.1002/alz70856_104001},
pmid = {41453230},
issn = {1552-5279},
mesh = {Humans ; Female ; *Amyloid beta-Peptides/blood ; Male ; Aged ; Biomarkers/blood ; Aged, 80 and over ; *Peptide Fragments/blood ; *Diet, Mediterranean ; Alzheimer Disease/blood ; Longitudinal Studies ; },
abstract = {BACKGROUND: Plasma amyloid-beta (Abeta) reflects brain amyloid pathology, with a lower plasma Abeta42/40 ratio linked to a higher risk of Alzheimer's disease and related dementias (ADRD). This study investigates the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on the longitudinal changes in plasma Abeta 42/40 levels.

METHOD: MIND trial was a 3-year, two-site, randomized controlled clinical trial comparing the MIND diet with a usual diet in 604 participants aged 65 to 85 years with a family history of dementia but without cognitive impairment, being overweight and with suboptimal diets at baseline; both diets promoted weight loss through mild caloric restriction. MIND diet intervention promoted 9 brain-healthy food groups (e.g., green leafy vegetables, nuts, berries) and limited consumption of 5 unhealthy food groups (e.g., red and processed meats, fried foods). Multivariable-adjusted linear mixed-effect models with a random intercept were utilized to estimate the effect of dietary interventions on the rate of change in plasma Abeta42/40 levels during the 3-year trial period.

RESULT: Of 604 individuals enrolled in the trial, 598 had measured plasma levels of A 42 and 40 at the baseline and 504 (84.3%) at the end of the trial (year 3). The average (SD) age at enrollment was 70.4 (4.2) years; 388 (64.9%) were female, and 524 (87.6%) were white individuals. At the baseline, Abeta42/40 levels were similar in people randomized to the MIND diet group (mean = 0.069 pg/ml) and those in the control group (mean = 0.068 pg/ml). At year 3, Abeta42/40 levels decreased in the control group while remaining statistically unchanged in the MIND diet group. Compared to the individuals in the MIND diet group, those in the control group showed an average 2.8% decline in plasma Abeta42/40 levels (beta= -0.012; SE = 0.005; p-value=0.024) over a 3-year follow-up period.

CONCLUSION: This study showed that dietary intervention influences longitudinal changes in plasma Abeta 42/40 levels. Compared to the MIND diet group, individuals in the control group showed a modest decline in plasma Abeta 42/40 levels, suggesting that the MIND diet intervention may reduce Alzheimer's disease pathology in the brain and, potentially, the risk of ADRD.},
}

Humans
Female
*Amyloid beta-Peptides/blood
Male
Aged
Biomarkers/blood
Aged, 80 and over
*Peptide Fragments/blood
*Diet, Mediterranean
Alzheimer Disease/blood
Longitudinal Studies

@article {pmid41453224,
year = {2025},
author = {Namboodiri, S and Kaur, N and Kaur, A and Randhawa, J and Kaler, P and Weakley, A},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107725},
doi = {10.1002/alz70858_107725},
pmid = {41453224},
issn = {1552-5279},
mesh = {Humans ; *Caregivers/psychology ; Male ; Female ; Middle Aged ; Surveys and Questionnaires ; *Dementia/nursing/psychology ; Aged ; Stress, Psychological/psychology ; *Asian/psychology ; Adult ; *Family/psychology ; },
abstract = {BACKGROUND: South Asian (SA) family caregivers living in the U.S. are understudied despite being a fast-growing population with a disproportionate risk of Alzheimer's disease. The primary aim of this study was to characterize care practices, preferences, and psychological wellbeing among SA caregivers providing care to older generation family members. Given the collectivist nature of SA cultures, we expected most caregivers to live with their care partners and prefer similar, family-based care for their future.

METHOD: Community outreach and an Asian American caregiver registry (CARES) were used for recruitment. Participants completed questionnaires asking about caregiving practices (e.g., frequency, involvement), perspective on their personal future care (evaluated on a 1-5 scale where 1=strongly agree and 5=strongly disagree), and caregiver stress/strain (Zarit Burden Interview).

RESULT: Participants included 14 SA caregivers (age M = 49.5, SD = 15.5; education M = 17.1, SD = 2.3,). Seventy-one percent identified as 1[st] generation immigrant, 21% as 2[nd] generation, and 7% did not specify. Most caregivers provided care to parents/in-laws (79%). Common tasks requiring assistance were transportation (100% of caregivers surveyed) medical appointments (93%), cooking and medication management (71% for both). Seventy-one percent provided physical support, whereas 57% provided support for cognitive limitations. Regarding future care, 43% of participants want to live with their family (non-spouse) in the future, and this desire was significantly correlated with currently co-residing with their care partner (r = -.68, p = .01). Sixty-four percent indicate they would like to live alone/with spouse and 54% desire to not live in a retirement community. Mild to moderate levels of stress/strain were endorsed overall (M = 14.2, SD = 9.4), and were significantly correlated with a future care preference of living alone/with spouse (r = -.820, p < .001).

CONCLUSION: In our sample, SA caregivers primarily live with the older generation family member they care for. Although less than half of the participants desire to live with family beyond their spouse in the future, currently providing in-home care increased likelihood of wanting similar care. Importantly, caregiver stress/strain strongly increased desire to live alone/with spouse. These findings suggest that caregiver wellbeing influences desires for future care, potentially resulting in perspectives that are not in-line with cultural values. As such, culturally tailored interventions are recommended to meet everyday care needs.},
}

Humans
*Caregivers/psychology
Male
Female
Middle Aged
Surveys and Questionnaires
*Dementia/nursing/psychology
Aged
Stress, Psychological/psychology
*Asian/psychology
Adult
*Family/psychology

@article {pmid41453220,
year = {2025},
author = {Newton, RL and Beyl, R and Hodoh, F and Hartford, M and Carmichael, OT},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107771},
doi = {10.1002/alz70858_107771},
pmid = {41453220},
issn = {1552-5279},
mesh = {Humans ; Aged ; Female ; Male ; *Black or African American/psychology ; *Patient Selection ; COVID-19 ; *Dementia/psychology/therapy ; Middle Aged ; *Alzheimer Disease/prevention & control ; Exercise ; White ; },
abstract = {BACKGROUND: African Americans are underrepresented in aging research. Few studies have assessed methods for recruiting older African Americans into clinical trials. The Reducing African Americans' Alzheimer's Disease Risk Through Exercise (RAATE) study is a year-long, randomized controlled trial that exclusively enrolled sedentary, cognitively healthy older African Americans and provides an opportunity to assess the effectiveness of various recruitment methods.

METHOD: Community-based strategies which included attending community events, churches, health fairs, and strategic placement of flyers were implemented by a designated recruiter. The academic institution implemented media-based strategies including listserv emails, emails to past participants, social media, postcard mailouts, and advertisements on the institutional website, TV, and newspaper. Recruitment occurred from September 2019 - November 2024, with a year-long pause due to the COVID pandemic.

RESULT: There were 608 older African American adults who screened for the study and 129 were enrolled (mean age 68 +/- 5 years; 76% female; 34% with income < $50k/year; 45% married). The recruitment strategies that resulted in the greatest number of screeners included email (25.2%), friend/family (11.5%), community event (10.7%), past participant (10.2%), and social media (9.0%). The recruitment strategies that resulted in the greatest number of screeners included email (28.0%), family/friend (15.5%), social media (11.7%), past participant (7.8%), and community event (7.0%). Media-based methods which are largely electronic, including email, social media, and contacting past participants, accounted for 44.3% and 47.4% of screeners and enrollees, respectively. Community based efforts, including community events, church, and health fairs were responsible for 27.5% of screeners and 16.4% of enrolled participants.

CONCLUSION: The participant's high education level or the increased reach of electronic media into older populations may have contributed to the effectiveness of these methods. Community-based efforts have historically been the most effective means of recruiting this population. It is believed that the pandemic limited the effectiveness of these efforts. These data suggest that a variety of strategies are important for recruiting an underrepresented group into a year-long non-pharmacological clinical trial.},
}

Humans
Aged
Female
Male
*Black or African American/psychology
*Patient Selection
COVID-19
*Dementia/psychology/therapy
Middle Aged
*Alzheimer Disease/prevention & control
Exercise
White

@article {pmid41453218,
year = {2025},
author = {Mai, Y and Cao, Z and Yu, Q and Liu, J},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104134},
doi = {10.1002/alz70856_104134},
pmid = {41453218},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/blood/diagnosis/metabolism ; *Cognitive Dysfunction/blood/metabolism/diagnosis ; *Biomarkers/blood ; Male ; Female ; Aged ; Metabolomics/methods ; Cohort Studies ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are leading causes of dementia in the elderly worldwide, characterized by abnormal cognition and behavior, which complicates diagnosis and treatment. Metabolites play a critical role in cellular process related to the pathogenesis of AD and MCI. However, the metabolic alterations, particularly in lipid metabolism, in AD and MCI are poorly understood.

METHOD: In this study, we applied a quantitative and targeted metabolomics approach to a cohort of AD patients (n = 22), MCI patients (n = 19) and cognitively normal (CN) (n = 19) using ultra-performance liquid chromatography triple quadrupole mass spectrometry to identify metabolic changes associated with AD and MCI.

RESULT: Compared to CN, we identified 32 differential metabolites in AD and 49 in MCI serum. Notably, differential metabolites related to AA, organic acid, FA, phosphatidylcholine (PC), sphingomyelin (SM) metabolism in AD and free fatty acid (FFA), acylcarnitine, PC, SM in MCI were strongly associated with cognitive level, memory, attention and execution function as evaluated by scales including Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-cognitive Section (ADAS), the Montreal Cognitive Assessment (MoCA), the Clinical Dementia Rating (CDR), the Auditory Verbal Learning Test (AVLT) and the Trail Making Test (TMT). Pathway analysis based on the differential metabolites revealed perturbation in pathways related to phospholipid metabolism, sphingolipid metabolism, amino acids (AAs) metabolism, beta oxidation of FAs, and carnitine metabolism. Using random forest (RF), support vector machine (SVM) and Boruta analysis for classification and validated by gradient boosting (GB), logistic regression (LR) and random forest diagnostic model, we identified panels of 10 metabolites in AD and 13 metabolites in MCI that effectively discriminate AD and MCI individuals from CN with high accuracy, sensitivity and specificity.

CONCLUSION: In summary, this novel study combing metabolomics and lipidomics approaches and found that perturbations in serum sphignolipids, glycerophospholipids, AAs, FFA and acylcarnitines are consistently associated with pathology and progression of AD and MCI. These metabolic biomarkers provided promising molecular targets for the early diagnosis and treatment of AD and MCI.},
}

Humans
*Alzheimer Disease/blood/diagnosis/metabolism
*Cognitive Dysfunction/blood/metabolism/diagnosis
*Biomarkers/blood
Male
Female
Aged
Metabolomics/methods
Cohort Studies

@article {pmid41453217,
year = {2025},
author = {Meghdadi, AH and Ma, C and Thunen, EJ and Hamilton, JM and Boeve, BF and St Louis, EK and Fischer, C and Salat, DH and Berka, C},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103986},
doi = {10.1002/alz70856_103986},
pmid = {41453217},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/physiopathology/diagnosis ; *Alzheimer Disease/physiopathology/diagnosis ; Aged ; Biomarkers ; *Theta Rhythm/physiology ; Electroencephalography ; Middle Aged ; Aged, 80 and over ; *Brain/physiopathology ; },
abstract = {BACKGROUND: Healthy aging and cognitive decline in Alzheimer's Disease (AD) and its precursor, Mild Cognitive Impairment (MCI), are linked to changes in resting-state EEG power spectral density (PSD). Theta band (3-7 Hz) power decreases with normal aging but increases with cognitive decline. However, frequency content does not always indicate true oscillatory activity. Oscillations reflect power concentration at a specific frequency, appearing as peaks in the frequency domain and visible rhythms in the time domain. Rhythmicity analysis quantifies oscillation persistence (percentage of time observed) independently of power. This study examined Theta power and Theta rhythms in healthy controls (HC) versus individuals with MCI/AD.

METHOD: Participants included 32 AD, 88 MCI, and 115 and age- matched HC, who completed 5-minutes of resting-state eyes-closed EEG at their baseline visit. PSD was computed for one-second epochs. Relative Theta power was defined as the proportion of total power in the Theta band, averaging across epochs. Theta rhythm duration was defined as the percentage of epochs with Theta oscillations. Baseline differences and longitudinal changes were analyzed for a subset of participants: 28 MCI and 5 AD with at least one follow-up visit, and 25 HC with at least two follow-ups.

RESULT: At baseline, the MCI/AD group exhibited significantly higher relative Theta power (p <0.01, df=233, ES=0.35 at T6) and a greater Theta rhythm duration (p <0.01, df=231, ES=0.41 at T6) compared to HC. Longitudinally, HC exhibited a significant reduction in Theta power by the second follow-up (p <0.05, df=24, ES=0.51 at Cz), with no significant changes in Theta rhythms duration. In contrast, MCI/AD showed a significant increase in Theta rhythm duration (and not power) at first follow-up visit (p < 0.05, df =32, ES=0.30 at T3).

CONCLUSION: Theta power and Theta rhythm duration are both linked to cognitive decline in MCI and AD but differ from healthy aging patterns. While Theta power reflects age-related changes, Theta rhythms duration may serve as a specific biomarker for disease progression in MCI and AD. These findings support the value of Rhythmicity analysis in EEG-based biomarkers of cognitive decline.},
}

Humans
Male
Female
*Cognitive Dysfunction/physiopathology/diagnosis
*Alzheimer Disease/physiopathology/diagnosis
Aged
Biomarkers
*Theta Rhythm/physiology
Electroencephalography
Middle Aged
Aged, 80 and over
*Brain/physiopathology

@article {pmid41453213,
year = {2025},
author = {Noshin, A},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107748},
doi = {10.1002/alz70858_107748},
pmid = {41453213},
issn = {1552-5279},
mesh = {Humans ; *Cognitive Reserve/physiology ; *Mobile Applications ; *Dementia/psychology ; *Alzheimer Disease/psychology/prevention & control ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Cognitive Reserve (CR) is the brain's inherent capacity to withstand neurological changes and maintain cognitive functionality despite pathological or age related changes. It also provides valuable insight into one's resilience to Alzheimer's disease pathology. Epidemiological research indicates, attainment of higher cognitive reserve reduces the risk of developing Alzheimer's disease by maintaining better brain functionality.

METHODS: Here, we propose a novel mobile application, Cognitive Reserve Measurement, designed for comprehensive assessment, longitudinal monitoring and targeted augmentation of CR to alleviate the risk of Alzheimer's disease. To meticulously track behaviours germane to cognitive well-being, our application employs interfaces like a home screen, journal data, and game screen to encourage user engagement and regular participation in cognition-boosting activities. The established Cognitive Reserve Index Questionnaire (CRIq) is seamlessly integrated to provide a robust quantitative evaluation.

RESULTS: App was developed using Flutter and Dart for cross-platform functionality, the application's backend relies on Firebase for secure and real-time storage of user data, such as journal entries and CRI scores. Ensuring data security is a top priority given the sensitive nature of cognitive health. Upon initial setup, user's attain their baseline based score on Cognitive Reserve Index Questionnaire (CRIq) score. The Journal section prompts users daily to reflect on activities from the previous day and the Journal Data section is for tracking activities that influence cognitive health shall purposefully track user habits stimulus for CR (e.g. regular physical activity, social engagement, sleep regimen, stress management etc.) and progress over time through sophisticated data visualization. Users can also engage in brain training games designed to enhance memory and reasoning skills. Currently the app is in the testing phase with a prototype being evaluated for usability and engagement to promote cognitive resilience and support healthy aging.

CONCLUSION: Aiming to address the escalating global need for effective cognitive health intervention within an increasing geriatric population, the application leverages the accessibility of mobile technology and provides a tool for precise measurement and optimization of CR. The foundational rationale for this application underscores the pivotal role of CR in preserving healthy brain functionality across lifespan, eventually preventing or delaying Alzheimer's disease onset.},
}

Humans
*Cognitive Reserve/physiology
*Mobile Applications
*Dementia/psychology
*Alzheimer Disease/psychology/prevention & control
Surveys and Questionnaires

@article {pmid41453212,
year = {2025},
author = {Capurro, L and Radloff, M and Brusco, LI and Ramele, R and Forcato, C},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104444},
doi = {10.1002/alz70856_104444},
pmid = {41453212},
issn = {1552-5279},
mesh = {Humans ; Aged ; Male ; Electroencephalography ; Female ; Adult ; *Aging/physiology ; Biomarkers ; Young Adult ; *Brain/physiology ; Middle Aged ; Aged, 80 and over ; Glymphatic System/physiology ; },
abstract = {BACKGROUND: The oscillatory nature of slow waves during non-rapid eye movement (NREM) sleep has recently been proposed as crucial for the glymphatic system, facilitating the clearance of metabolic waste from the brain. While aging-related reductions in slow wave quantity and amplitude are well-documented and linked to this cleansing function, we propose that the rhythmic dynamics in which slow waves occur may also play a critical role.

METHOD: Thus, we introduce a novel classification of slow waves based on their temporal dynamics, categorizing them into isolated waves and oscillation trains. Using overnight EEG recordings from young and elderly adults, we compared the proportions of these wave types. Additionally, we analyzed train composition, including the proportion of slow waves that initiate a train (lead waves) and the lengths of the oscillation trains (number of consecutive slow waves initiated by one lead wave).

RESULT: Our results revealed that elderly adults exhibited a higher prevalence of isolated waves and a lower proportion of oscillation trains. Moreover, while elderly adults showed a higher proportion of lead waves, their oscillation trains were significantly shorter compared to those of young adults.

CONCLUSION: We propose that natural aging may result in a less oscillatory brain state, characterized by a diminished ability to produce sustained, periodic oscillations. This diminished rhythmicity could impair cerebrospinal fluid pulsation, potentially reducing the brain's ability to efficiently clear pathogenic substances during sleep. Given the established link between impaired glymphatic clearance and neurodegenerative diseases such as Alzheimer's, this diminished capacity to sustain slow wave trains may contribute to age-related decline in neurological functioning.},
}

Humans
Aged
Male
Electroencephalography
Female
Adult
*Aging/physiology
Biomarkers
Young Adult
*Brain/physiology
Middle Aged
Aged, 80 and over
Glymphatic System/physiology

@article {pmid41453211,
year = {2025},
author = {Goldstein, A and Krahn, EA and Rezaii, N and Eldaief, MC and McGinnis, SM and O'Chander, R and Wong, B and Dickerson, BC},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106208},
doi = {10.1002/alz70858_106208},
pmid = {41453211},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Aged ; Telemedicine ; Neuropsychological Tests ; Prospective Studies ; *Alzheimer Disease/drug therapy/psychology ; Surveys and Questionnaires ; Aged, 80 and over ; Middle Aged ; },
abstract = {BACKGROUND: Anti-amyloid disease-modifying therapies (DMTs) for Alzheimer's Disease (AD) such as lecanemab are being increasingly prescribed. This mandates more frequent and in-depth tracking of patients receiving these agents in order to better estimate their cognitive, behavioral, and functional trajectories while receiving treatment. Here we report the feasibility of a frequent cognitive testing protocol by telehealth for AD patients receiving lecanemab.

METHOD: 18 AD patients receiving lecanemab as part of their clinical care were enrolled in a prospective observational study. Participants completed validated questionnaires assessing cognition, mood, behavior, and functional status (Amsterdam IADL; NPIQ) in REDCap prior to their baseline telehealth cognitive assessment. Following their baseline session, telehealth assessments were performed every 3 months, and included a modified AD Assessment Scale-Cognitive (ADAS-Cog) (with alternate forms at each timepoint, in keeping with the procedures often used in AD clinical trials). Baseline and monthly testing sessions included additional tests of memory, language, and executive function with alternate forms through the platform SurveyLex. For each telehealth session, participants viewed task stimuli over Zoom with the examiner present; responses were audio recorded by the SurveyLex software.

RESULT: 34 potential participants have been screened thus far. 24% declined participation due to the demands of testing and timing. 53% have enrolled (55% female; average age=67.2 ± 9.5 years). Participants included a range of AD syndromes (MCI/mild-dementia, PCA, PPA). Average MoCA score of those enrolled (obtained prior to beginning infusions) was 19.2 ± 4.92. Baseline and 3-month sessions lasted an average of 67.07 minutes (range: 45-120 minutes), while shorter monthly sessions by SurveyLex lasted an average of 34.93 minutes (range: 24-45 minutes). Five participants withdrew due to the demands of testing; mean MoCA score for these participants was 20.8 ± 5.26 (range: 14-27). Enrolled participants have completed an average of 3.6 monthly visits thus far (range: 1-9).

CONCLUSION: Preliminary results indicate that frequent remote cognitive testing of AD patients receiving lecanemab is feasible. Compliance appears to be moderate with 61% of participants remaining enrolled 3 months after their first visit. We propose remote monthly assessments as a new model to monitor patients receiving DMTs for AD.},
}

Humans
Female
Male
Aged
Telemedicine
Neuropsychological Tests
Prospective Studies
*Alzheimer Disease/drug therapy/psychology
Surveys and Questionnaires
Aged, 80 and over
Middle Aged

@article {pmid41453200,
year = {2025},
author = {Cody, K and Sokolowski, A and Winer, JR and Young, CB and Younes, K and Durant, A and Dumitrescu, L and Archer, D and Tosun, D and Johnson, SC and Harrison, TM and Hohman, TJ and Mormino, EC},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104202},
doi = {10.1002/alz70856_104202},
pmid = {41453200},
issn = {1552-5279},
mesh = {Humans ; Positron-Emission Tomography ; *tau Proteins/metabolism ; Female ; Male ; *Alzheimer Disease/diagnostic imaging/metabolism ; Aged ; Biomarkers/metabolism ; Aged, 80 and over ; *Brain/diagnostic imaging/metabolism ; Amyloid beta-Peptides/metabolism ; Magnetic Resonance Imaging ; Middle Aged ; },
abstract = {BACKGROUND: This study characterizes the frequency of amyloid and tau PET-based stages along the clinical continuum in NACC participants from the Alzheimer's Disease Research Center (ADRC) program.

METHOD: 1013 NACC participants with available amyloid and tau PET imaging and diagnosis data were included in this study. Given the clinical heterogeneity present across NACC, parallel analyses were conducted in ADNI for comparison (n = 926; Table 1). PET data corresponding to ligand-specific post-injection windows were processed and harmonized across cohorts using an MRI-free pipeline. Amyloid PET SUVRs were translated to centiloids (CLs). Amyloid positivity (A+/-) was defined as 25CL. Regional tau positivity (T+/-) was derived within ligand using Gaussian mixture modeling. A hierarchical staging schema was used to classify tau positivity (e.g., T-, T12+, T34+, T56+) and create PET-based biological stages (e.g., Stage A: A+T-; Stage B: A+T12+; Stage C: A+T34+; Stage D: A+T56+). The frequency of PET-based stages was examined across clinical stages and compared between cohorts. Ordinal logistic regression models were used to estimate the cumulative prevalence of biological stages according to age (mean-centered), cohort, and clinical stage.

RESULT: Compared to ADNI, NACC had twice as many individuals with dementia (Table 1), of which 35% were presumed to be due to non-AD suspected etiologies (Figure 1A). Across cohorts, tau PET stages generally increased with both amyloid and clinical severity (Figure 1B). Notably, the frequency of biological stages within dementia differed significantly between cohorts such that NACC had a significantly higher proportion of participants in Stage D, while ADNI had more participants in Stages A-C (χ[2](3)=11.5, p = 0.009; Figure 2A). Analyses estimating the prevalence of biological stages reflected this difference in the distribution of biological stages across clinical stages between cohorts (cohort×clinical stage, p <.001). The estimated prevalence of the biological stages also differed by age and clinical stage (age×clinical stage, p <.001), with younger age associated with higher probability of Stage D in dementia across both cohorts (Figure 2B).

CONCLUSION: Together, these findings underscore heterogeneity in amyloid and tau PET burden along the clinical continuum and highlight the application of amyloid and tau PET-based staging frameworks in a clinically heterogeneous sample.},
}

Humans
Positron-Emission Tomography
*tau Proteins/metabolism
Female
Male
*Alzheimer Disease/diagnostic imaging/metabolism
Aged
Biomarkers/metabolism
Aged, 80 and over
*Brain/diagnostic imaging/metabolism
Amyloid beta-Peptides/metabolism
Magnetic Resonance Imaging
Middle Aged

@article {pmid41453186,
year = {2025},
author = {Yuchuan, W and Mitchell, HJ and Lee, S and Zeng, Z and Miller, PJ and Bennacef, I and Riffel, K and Purcell, ML and Haley, HD and Gantert, LT and Marie, HA and Meng, X and Stenslik, M and Ma, LM and Fay, JF and Li, W and Marcus, J and Smith, SM and Uslaner, JM and Drolet, RE and Hostetler, ED},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103695},
doi = {10.1002/alz70856_103695},
pmid = {41453186},
issn = {1552-5279},
mesh = {Animals ; *Positron-Emission Tomography/methods ; Humans ; *Brain/diagnostic imaging/metabolism/pathology ; *Parkinson Disease/diagnostic imaging/metabolism/pathology ; *Alzheimer Disease/diagnostic imaging/metabolism/pathology ; Mice ; Biomarkers/metabolism ; Mice, Transgenic ; Male ; Female ; Aged ; *alpha-Synuclein/metabolism ; Disease Models, Animal ; Radiopharmaceuticals ; Middle Aged ; },
abstract = {BACKGROUND: To date, clinical feasibility of imaging Lewy-body pathology and related disease progression in Parkinson's disease (PD) patients remains unclear. Supported by the Michael J. Fox Foundation through Ken Griffin Alpha-Synuclein (ASYN) Imaging Award, we developed [[11]C]MK-7337, a PET radioligand with high-affinity to ASYN, and performed a first-in-human (FIH) study to determine if imaging relevant pathology in patients with mild to moderate PD was feasible.

METHOD: Radioligand binding experiments with [[3]H]MK-7337 were conducted in postmortem PD, Alzheimer's disease, and non-diseased brain tissues to profile affinity and selectivity. PET imaging in the A30P (ASYN overexpressing-transgenic) mouse model was utilized to validate the in vivo performance of tracer binding to ASYN pathology. PET imaging in pathology-free non-human primates (NHP) were performed to assess tracer translational suitability for PET imaging of human brains. For the FIH study, a total of eight PD (ASYN SAA+, DAT scan+, H&Y 2-3, on stable PD Rx) and four healthy-elderly (HE) participants were imaged. [[11]C]MK-7337 PET tracer uptake patterns in the brains of PD and HE participants were compared by standardized uptake value ratio (SUVR) using cortical white matter as a pseudo reference region.

RESULT: In vitro tissue binding studies revealed MK-7337 possessed high affinity (<1 nM) for ASYN pathology with moderate liability of off-target binding. PET imaging in aged A30P mice demonstrated robust displaceable tracer binding in the midbrain/brainstem regions, which had known ASYN pathology. PET imaging in NHP suggested suitable tracer brain kinetics, as well as moderate off-target binding liabilities in vivo. The FIH study confirmed the suitable tracer kinetics of [[11]C]MK-7337 in human brains, with peak SUV>1 in all scans. Similar patterns of tracer brain distribution and clearance were observed between HE and preclinical NHP PET scans. PD participants revealed elevated SUVRs (when compared to HE) in regions believed to contain early ASYN pathology, specifically the midbrain (including substantia nigra), brainstem/pons, and olfactory epithelium regions.

CONCLUSION: [[11]C]MK-7337 has demonstrated the feasibility of using a high-affinity ASYN PET radioligand to image alpha-synuclein pathology in PD patients.},
}

Animals
*Positron-Emission Tomography/methods
Humans
*Brain/diagnostic imaging/metabolism/pathology
*Parkinson Disease/diagnostic imaging/metabolism/pathology
*Alzheimer Disease/diagnostic imaging/metabolism/pathology
Mice
Biomarkers/metabolism
Mice, Transgenic
Male
Female
Aged
*alpha-Synuclein/metabolism
Disease Models, Animal
Radiopharmaceuticals
Middle Aged

@article {pmid41453185,
year = {2025},
author = {Liou, JJ and Santini, T and Ikonomovic, MD and Villemagne, VL and Cohen, AD and Laymon, CM and Minhas, DS and Luo, W and Tudorascu, DL and Handen, BL and Lopez, OL and Yong, WH and Mapstone, M and Christian, BT and Hartley, SL and Brickman, A and Price, JC and Rosas, HD and Lai, F and Zaman, S and Head, E and Kofler, JK and Ibrahim, TS},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103737},
doi = {10.1002/alz70856_103737},
pmid = {41453185},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; Biomarkers/metabolism ; *Cognitive Dysfunction/pathology/diagnostic imaging/metabolism ; Positron-Emission Tomography ; *Alzheimer Disease/pathology/diagnostic imaging/metabolism ; *Amyloid beta-Peptides/metabolism ; *Down Syndrome/pathology/diagnostic imaging/metabolism ; Hippocampus/pathology/diagnostic imaging ; Aged, 80 and over ; Middle Aged ; Aniline Compounds ; Amygdala/pathology/diagnostic imaging ; *Brain/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: In late-onset AD, β-amyloid (Aβ) deposition is associated with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), beginning in the amygdala and spreading to the hippocampus and neocortex. The association in Down syndrome (DS) remains unexamined. People with DS are genetically predisposed to early AD, with Aβ accumulation occurring at younger ages. This study investigates the relationship between Aβ deposition and postmortem volumes or neuropathologic changes in DS and late-onset AD.

METHODS: Demographic and clinical diagnoses-cognitively stable (CS), mild cognitive impairment (MCI), and dementia-were collected from the Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) and Pittsburgh Alzheimer's Disease Research Center (ADRC). Results of Aβ PET scans with 11C-Pittsburgh compound B and 18F-florbetapir were expressed in centiloids. Amygdala and hippocampus were manually segmented from postmortem ex vivo 7-tesla MRI. Histopathology included Thal phase, Braak NFT stage, CERAD score, LATE-NC stage, hippocampal sclerosis, Lewy body stage, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. T-tests, linear regressions, and ANCOVA were performed to compare cohorts, examine associations between Aβ and MRI or neuropathology metrics, and compare regression slopes of two cohorts.

RESULTS: The ABC-DS cohort showed similar Aβ PET burden but had a lower prevalence of ApoE4 carriers, younger age at clinical diagnosis and autopsy, shorter PET-autopsy interval, smaller amygdala and hippocampal volumes, more advanced CERAD scores, and no atherosclerosis compared to ADRC cohort (Figure 1). In our existing datasets, the association between age at PET scan and Aβ burden did not reach statistical significance likely due to limited sample size. Antemortem Aβ burden was not associated with postmortem amygdala or hippocampal volumes in either group (Figure 2). Higher Aβ burden was associated with advanced LATE-NC stage in ABC-DS but not in ADRC. In ADRC, Aβ burden correlated with postmortem Aβ plaque, neurofibrillary tangles, and neuritic plaques, while no significant associations were found in ABC-DS for Thal phase, Braak NFT stage, or CERAD score (Figure 3).

CONCLUSIONS: In DS, antemortem Aβ PET burden is associated with advanced LATE-NC stage but not with postmortem amygdala or hippocampal volumes. In ADRC cohort, Aβ burden correlates with postmortem amyloid plaque, neurofibrillary tangle, and neuritic plaque pathology.},
}

Humans
Male
Female
Aged
Biomarkers/metabolism
*Cognitive Dysfunction/pathology/diagnostic imaging/metabolism
Positron-Emission Tomography
*Alzheimer Disease/pathology/diagnostic imaging/metabolism
*Amyloid beta-Peptides/metabolism
*Down Syndrome/pathology/diagnostic imaging/metabolism
Hippocampus/pathology/diagnostic imaging
Aged, 80 and over
Middle Aged
Aniline Compounds
Amygdala/pathology/diagnostic imaging
*Brain/pathology/diagnostic imaging

@article {pmid41453179,
year = {2025},
author = {Ligason-Tiquia, A and Pachicano, M and Taylor-Munoz, E and Chui, HC and Joe, EB},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106749},
doi = {10.1002/alz70858_106749},
pmid = {41453179},
issn = {1552-5279},
mesh = {Humans ; *Dementia/psychology/therapy ; Female ; Male ; Surveys and Questionnaires ; Longitudinal Studies ; Aged ; *Biomedical Research ; },
abstract = {BACKGROUND: Longitudinal studies of aging and cognition depend on high rates of participant retention. We conducted surveys of participants in observational research studies through USC's Alzheimer's Disease Research Center (ADRC) to assess their overall experience with research involvement.

METHOD: 3 waves of participant feedback surveys were conducted over a 4 year period. Surveys were mailed to English-speaking participants without dementia enrolled in the ADRC and affiliated longitudinal biomarker-based studies. Respondents completed surveys asking them to describe their experience with study staff, participation logistics, and individual research procedures. Two raters coded free text responses thematically and discrepancies were reconciled by consensus.

RESULT: Results from 222 surveys were analyzed. Key themes associated with a positive experience with research participation were staff qualities, such as professionalism and warmth, and a sense of partnership with the research team. Negative comments primarily related to staff turnover, communication, inconvenience, and discomfort from study procedures, such as MRI noise or spinal headache after lumbar puncture. In addition, some responses reflected a desire for more streamlined disclosure of research results, or demonstrated a lack of clarity of the relationship between research and clinical care.

CONCLUSION: While most respondents had positive experiences with research participation, a number of modifiable factors were associated with negative participant experience. Identifying facilitators and barriers of research participation may improve participant retention in longitudinal studies of aging research.},
}

Humans
*Dementia/psychology/therapy
Female
Male
Surveys and Questionnaires
Longitudinal Studies
Aged
*Biomedical Research

@article {pmid41453176,
year = {2025},
author = {Ghahremani, M and Ismail, Z},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103852},
doi = {10.1002/alz70856_103852},
pmid = {41453176},
issn = {1552-5279},
mesh = {Humans ; Female ; *Biomarkers/cerebrospinal fluid ; Male ; Aged ; *Amyloid beta-Peptides/cerebrospinal fluid ; *tau Proteins/cerebrospinal fluid ; Cross-Sectional Studies ; *Alzheimer Disease/cerebrospinal fluid/diagnosis ; *Peptide Fragments/cerebrospinal fluid ; *Cognitive Dysfunction/cerebrospinal fluid ; Aged, 80 and over ; Apolipoprotein E4/genetics ; },
abstract = {BACKGROUND: Dementia research is increasingly focused on developing methods for the early identification of individuals with underlying Alzheimer's disease (AD) pathology. Functional impairment (FI) is a key criterion for diagnosing dementia. However, subtle changes in function may occur during the preclinical and prodromal phases but are often not accurately characterized. Furthermore, there are few studies investigating the association between these subtle changes in functional abilities and AD biofluid biomarkers. Here we examined cross-sectional associations between established cerebrospinal fluid (CSF) AD biomarkers and persistent versus transient FI in dementia-free older adults.

METHOD: Data from 1001 individuals (mean age 72.9±7.0; 45.2% female; 62.6% MCI; 41.5% APOE-e4 carrier) from the Alzheimer's Disease Neuroimaging Initiative were analyzed. CSF biomarkers of interest included p-tau181, amyloid-beta42 (Aβ42), and the ptau-181/Aβ42 ratio. Participants without baseline biomarker data were excluded. Using factor analysis, Functional Activities Questionnaire items of preparing meals, heating water to make warm beverages, and shopping were selected to quantify function. Persistent FI was operationalized as FI present at >two-thirds of visits prior to dementia. Comparator groups included Transient-FI and No-FI. Linear regression modeled the association between FI status and biomarker levels at baseline, adjusting for age, sex, education, cognition, and APOE-e4 status.

RESULT: Compared to no FI, Persistent FI was associated with significantly higher p-tau181 levels (Beta=10.77; CI[0.44-22.16]; p = 0.041) and lower Aβ42 levels (Beta=-8.72; 95%CI: [-13.86- -3.83]; p <0.001) at baseline, while transient FI was not (p-tau181: p = 0.503; Aβ42: p = 0.513). Similarly, Persistent FI was associated with a significantly higher ptau181/Aβ42 ratio (Beta=21.35; 95%CI: [6.79-37.89]; p = 0.003), which demonstrated the greatest effect size among all models. Transient FI did not show a significant association (p = 0.436) (Table 1).

CONCLUSION: Our cross-sectional findings contribute to the limited research on the association of FI with CSF biomarkers of AD in dementia-free older adults. Operationalizing FI-related risk based on persistence enhances prognostication and identifies high-risk individuals with greater burden of underlying AD pathology than those with transient FI or no FI. This approach may offer a more accurate method for early detection and stratification of at-risk individuals, potentially guiding interventions before the onset of dementia.},
}

Humans
Female
*Biomarkers/cerebrospinal fluid
Male
Aged
*Amyloid beta-Peptides/cerebrospinal fluid
*tau Proteins/cerebrospinal fluid
Cross-Sectional Studies
*Alzheimer Disease/cerebrospinal fluid/diagnosis
*Peptide Fragments/cerebrospinal fluid
*Cognitive Dysfunction/cerebrospinal fluid
Aged, 80 and over
Apolipoprotein E4/genetics

@article {pmid41453162,
year = {2025},
author = {Khan, AA},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107763},
doi = {10.1002/alz70858_107763},
pmid = {41453162},
issn = {1552-5279},
mesh = {Humans ; *Cognitive Reserve/physiology ; *Mobile Applications ; *Dementia/psychology ; *Alzheimer Disease/psychology/prevention & control ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Cognitive Reserve (CR) is the brain's inherent capacity to withstand neurological changes and maintain cognitive functionality despite pathological or age related changes. It also provides valuable insight into one's resilience to Alzheimer's disease pathology. Epidemiological research indicates, attainment of higher cognitive reserve reduces the risk of developing Alzheimer's disease by maintaining better brain functionality.

METHODS: Here, we propose a novel mobile application, Cognitive Reserve Measurement, designed for comprehensive assessment, longitudinal monitoring and targeted augmentation of CR to alleviate the risk of Alzheimer's disease. To meticulously track behaviours germane to cognitive well-being, our application employs interfaces like a home screen, journal data, and game screen to encourage user engagement and regular participation in cognition-boosting activities. The established Cognitive Reserve Index Questionnaire (CRIq) is seamlessly integrated to provide a robust quantitative evaluation.

RESULTS: App was developed using Flutter and Dart for cross-platform functionality, the application's backend relies on Firebase for secure and real-time storage of user data, such as journal entries and CRI scores. Ensuring data security is a top priority given the sensitive nature of cognitive health. Upon initial setup, user's attain their baseline based score on Cognitive Reserve Index Questionnaire (CRIq) score. The Journal section prompts users daily to reflect on activities from the previous day and the Journal Data section is for tracking activities that influence cognitive health shall purposefully track user habits stimulus for CR (e.g. regular physical activity, social engagement, sleep regimen, stress management etc.) and progress over time through sophisticated data visualization. Users can also engage in brain training games designed to enhance memory and reasoning skills. Currently the app is in the testing phase with a prototype being evaluated for usability and engagement to promote cognitive resilience and support healthy aging.

CONCLUSION: Aiming to address the escalating global need for effective cognitive health intervention within an increasing geriatric population, the application leverages the accessibility of mobile technology and provides a tool for precise measurement and optimization of CR. The foundational rationale for this application underscores the pivotal role of CR in preserving healthy brain functionality across lifespan, eventually preventing or delaying Alzheimer's disease onset.},
}

Humans
*Cognitive Reserve/physiology
*Mobile Applications
*Dementia/psychology
*Alzheimer Disease/psychology/prevention & control
Surveys and Questionnaires

@article {pmid41453151,
year = {2025},
author = {Brown, TM and James, SN and Nicholas, JM and Malone, IB and Coath, W and Murray-Smith, H and Cash, DM and Barkhof, F and Schott, JM and Barnes, J and Sudre, CH},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104402},
doi = {10.1002/alz70856_104402},
pmid = {41453151},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *White Matter/diagnostic imaging/pathology ; Aged ; Biomarkers ; *Alzheimer Disease/diagnostic imaging/pathology ; Diffusion Magnetic Resonance Imaging ; Middle Aged ; *Brain/pathology/diagnostic imaging ; Cohort Studies ; Amyloid beta-Peptides ; },
abstract = {BACKGROUND: Diffusion weighted imaging (DWI) measures white matter (WM) microstructure (WMMS), with changes in various DWI metrics seen in Alzheimer's disease (AD) progression[1]. Using data from Insight46[3-5], a British population-based birth cohort, we previously found poorer WMMS in normal appearing WM (NAWM) age 70 had sex-dependent associations with higher midlife blood pressure and cardiovascular risk, as well as concurrent WM hyperintensity volume (WMHV) and β-Amyloid (Aβ) burden[2]. Here we explore whether these findings reflect poorer WMMS in areas of NAWM that remained normal appearing ∼2.5 years later, or in areas that later became WMH.

METHOD: Using data from N = 302 Insight46 participants who were scanned for a second time ∼2.5 years later, we used linear regression to re-examine the previously identified significant relationships with NAWM integrity[2], as well as sex interactions in men and women that remained robust in the smaller follow-up sample, separately in "stable" (remained NAWM) and "converting" (converted to WMH) regions (Figure 1). WMMS metrics were fractional anisotropy (FA), mean diffusivity (MD) and neurite density index (NDI)[2]. Analyses were adjusted for sex and age as well as total intracranial volume (TIV) for models with WMHV and Aβ.

RESULT: Summary statistics are shown in Table 1. The associations shown in the total NAWM[2] persisted in stable regions (Figure 2). Stronger associations were observed in the converting NAWM, particularly with WMHV at age 70. There was also a significant association between BP at age 53 and FA and MD in males in the converting NAWM, which was only observed in women in the whole region[2]. The effect of Aβ on MD in men was robust in both regions.

CONCLUSION: Previously demonstrated associations with poorer WMMS (age, midlife cardiovascular risk factors, WMHV and Aβ)[2] were not driven solely by NAWM on the verge of becoming WMH. However, stronger effects observed in converting NAWM suggest higher midlife BP, poorer WMMS and WMH development are part of a continuous, related process, particularly in men. The similar effect of Aβ burden in men in the stable and unstable NAWM suggests the effects of Aβ on WMMI are not driven by tissue later converting to WMH.},
}

Humans
Female
Male
*White Matter/diagnostic imaging/pathology
Aged
Biomarkers
*Alzheimer Disease/diagnostic imaging/pathology
Diffusion Magnetic Resonance Imaging
Middle Aged
*Brain/pathology/diagnostic imaging
Cohort Studies
Amyloid beta-Peptides

@article {pmid41453150,
year = {2025},
author = {Carlisle, TC and Nair, KV and Sillau, SH and Giron, LL and Kwak, J and Tanabe, J and Holden, SK and Pelak, VS},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106083},
doi = {10.1002/alz70858_106083},
pmid = {41453150},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Aged ; *Dementia/psychology/drug therapy ; *Alzheimer Disease/drug therapy/psychology/diagnostic imaging ; Colorado ; Middle Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Clinical trials for FDA-approved anti-amyloid therapies (AATs) do not mirror the real-world experience of patients seen by dementia specialists. The unique Advanced Therapy in Neurodegenerative Disorders (ATND) Clinic at the University of Colorado staffed primarily by one dementia specialist shares its experience.

OBJECTIVES: To share the experience of the unique Advanced Therapy in Neurodegenerative Disorders (ATND) Clinic at the University of Colorado including characteristics and utilization of anti-amyloid therapies (lecanemab) between April 2024 - January 2025.

METHODS: Baseline characteristics including demographics, diagnostic assessments, lecanemab utilization, and Amyloid Related Imaging Abnormalities (ARIA) assessments were collected from ATND Clinic electronic medical records.

RESULTS: Patients were referred from the larger Memory Disorders Clinic at the University of Colorado, previously diagnosed with probable Alzheimer's disease, seen between April 2024 to January 2025 (n = 96) and not clearly meeting exclusion criteria for lecanemab. The current cohort includes those: in active diagnostic work-up, 25.0% (n = 24); currently being infused, 19.8% (n = 19); who declined treatment, 28.1% (n = 27), were determined ineligible, 9.4% (n = 9), who deferred treatment, 13.5% (n = 13); stopped/transferred treatment (as of January 2025), 4.2% (n = 4). Mean age was 71.5 (+/-8.0) years, with 52.1% women. Over half (59.4%) received a baseline MRI (undergoing the diagnostic work-up) and the majority (88.9%) underwent a lumbar puncture compared to 9.5% who had an amyloid positron emission tomography scan to establish biomarker confirmation of Alzheimer's. About a fifth (20.9%) with Apolipoprotein E (APOE4) data tested homozygous for the APOEe4 allele. Two patients experienced ARIA while receiving lecanemab. On average, infusing patients completed 12.2 (+/-7.2) infusions during the 10-month observation period. The mean number of days between the first consultation with the dementia specialist in the ATND Clinic and the baseline MRI was 31.6 (+/-23.1) (n = 47) days, and the first lecanemab infusion was 79.9 (+/-38.3) (n = 19) days. Patients declined AAT treatment because of homozygous APOEe4 status (37.0%) followed by concerns regarding modest efficacy (25.9%) and burden of treatment including cost (14.8%).

CONCLUSION: The ATND Clinic's experience in the first year of treatment provides real world data of AAT experience. Investment in hiring more dementia specialists can increase patient capacity for AAT evaluation and management.},
}

Humans
Female
Male
Aged
*Dementia/psychology/drug therapy
*Alzheimer Disease/drug therapy/psychology/diagnostic imaging
Colorado
Middle Aged
Aged, 80 and over

@article {pmid41453149,
year = {2025},
author = {Sandoval, R and Novikov, V and Attaran, A and Tabatabaei, MH and Eed, A and Cowan, M and Yau, MC and Abduldayem, Y and Sharma, S and Luo, W and Shlaifer, I and Evangelista, C and Durcan, TM and Fon, EA and Menon, RS and Chiosis, G and Bussey, TJ and Saksida, LM and Chakravarty, MM and Prado, VF and Prado, MA},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103517},
doi = {10.1002/alz70856_103517},
pmid = {41453149},
issn = {1552-5279},
mesh = {Animals ; Mice ; *Biomarkers/metabolism ; Mice, Transgenic ; Disease Models, Animal ; alpha-Synuclein/metabolism ; Brain/pathology/drug effects ; Male ; *Alzheimer Disease ; },
abstract = {BACKGROUND: Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation of misfolded proteins, including amyloid-β, tau, and alpha-synuclein (a-Syn). Despite extensive research, no effective disease-modifying therapies exist. A major barrier to drug development is the poor translatability of animal models and the lack of biomarkers with predictive power for clinical efficacy. Higher-order cognitive deficits, such as impaired reversal learning, are observed in patients with synucleinopathies, suggesting that cognitive biomarkers could be valuable in preclinical drug testing. This study evaluates whether touchscreen-based cognitive testing enhances the predictive validity of preclinical drug testing. We assessed PU-AD, an HSP90 epichaperome disruptor targeting the abnormal chaperone network implicated in protein misfolding disorders, and a mouse version of Cinpanemab, an anti-a-Syn antibody that recently failed in clinical trials, despite initial positive results in animal models.

METHOD: Hemizygous M83 transgenic mice were intracerebrally injected with preformed fibrils (PFFs) to model synucleinopathy-related neurodegeneration. Mice underwent cognitive assessment using the Pairwise Visual Discrimination and Reversal (PVD-R) touchscreen task, a highly translational measure of cognitive flexibility sensitive to a-Syn toxicity. PU-AD and Cinpanemab were administered intraperitoneally post-PFF injection. Drug doses matched previous animal model studies. Motor performance was assessed with grip strength, rotarod, and wire hang tests. MRI was used to detect brain atrophy. Immunohistochemical and biochemical analyses evaluated a-Syn pathology and neuroinflammation.

RESULT: M83/PFF-injected mice showed significant reversal learning deficits earlier than motor deficits. Pharmacokinetic analysis confirmed PU-AD reached brain concentrations comparable to those in other models. PU-AD treatment rescued cognitive and motor impairments, suggesting broad neuroprotective effects. In contrast, Cinpanemab-treated mice showed no improvements in cognition and preliminary data suggest no improvements in motor symptoms. Ongoing experiments are evaluating pathology and brain atrophy.

CONCLUSION: The lack of Cinpanemab efficacy in our pre-clinical testing pipeline aligns with clinical trial results. The effectiveness of PU-AD in reducing both cognitive and motor impairments suggests it may have broad therapeutic potential in synucleinopathies. We suggest that touchscreen-based cognitive testing enhances the predictive validity of preclinical drug evaluation.},
}

Animals
Mice
*Biomarkers/metabolism
Mice, Transgenic
Disease Models, Animal
alpha-Synuclein/metabolism
Brain/pathology/drug effects
Male
*Alzheimer Disease

@article {pmid41453148,
year = {2025},
author = {Vaqué-Alcázar, L and Del Hoyo, L and Videla, L and Benejam, B and Barroeta, I and Fernandez, S and Rodríguez-Baz, Í and Arranz, J and Arriola-Infante, JE and Maure-Blesa, L and Hernandez, AS and Morcillo-Nieto, AO and Bejanin, A and Lleó, A and Carmona-Iragui, M and Fortea, J},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106397},
doi = {10.1002/alz70858_106397},
pmid = {41453148},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Down Syndrome/psychology/complications/diagnosis ; Aged ; Middle Aged ; *Alzheimer Disease/diagnosis/psychology ; Spain ; Neuropsychological Tests ; Early Diagnosis ; Intellectual Disability/psychology ; Prodromal Symptoms ; Cohort Studies ; },
abstract = {BACKGROUND: Early diagnosis of symptomatic Alzheimer's disease (AD) in individuals with Down syndrome (DS) is crucial due to its near-universal occurrence and its significant impact on care planning and intervention strategies. This study examines the effects of key components of the screening health program implemented in Catalonia (Spain), with a particular focus on how diagnostic timing (first vs. follow-up visit) influences the age at clinical diagnosis, cognitive status, and the moderating role of intellectual disability (ID) level in this relationship.

METHOD: 205 (50.7% female) DS with prodromal AD (pDS) and 357 (50.1% female) with AD dementia (dDS) from the Down-Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort were split by the visit type when these diagnoses were made (first visit: NpDS=105, NdDS=219; along the follow-up visits: NpDS=100, NdDS=138). The Cambridge Cognitive Examination for Older Adults with Down's Syndrome (CAMCOG-DS) was used to assess the cognitive status among mild and moderate ID subjects. Parametric and non-parametric comparisons were made for age at diagnosis and CAMCOG-DS between patients receiving a diagnosis during the first vs. follow-up visits.

RESULT: Patients with pDS were younger than dDS (51.4±5.26 vs. 53.9±5.54; t = 2.509, p <0.001), with a larger difference during first visits (pDS=51.2±4.99 vs. dDS=54.1±5.72; t = 2.907, p <0.001) compared to follow-up visits (pDS=51.5±5.55 vs. dDS=53.4±5.23; t = 1.950, p = 0.033; Figure 1A). Among individuals with mild ID, those diagnosed at their first visit were younger than those diagnosed during follow-ups (t = 5.141, p = 0.042; Figure 1B). In contrast, for individuals with moderate, severe, or profound ID, diagnoses made at follow-up visits tended to occur at a younger age than those made during first visits (53.01±5.18 vs. 54.4±5.66, t = -1.335, p = 0.035; Figure 1B). Additionally, dDS diagnosed at their first visit had lower CAMCOG-DS total scores compared to follow-up diagnoses (44.1±17.80 vs. 57.5±14.62; U = 1190.50, p <0.001; Figure 2A). This difference remained significant only for the moderate ID group (41.4±16.36 vs. 52.6±13.35; z = 3.352, p = 0.002; Figure 2B). No significant effects were observed for pDS.

CONCLUSION: Longitudinal screening before AD symptoms start helps identify earlier AD clinical onset in DS depending on their ID level. Future research should address critical gaps in understanding the heterogeneity of premorbid cognition and key AD outcomes in this population.},
}

Humans
Female
Male
*Down Syndrome/psychology/complications/diagnosis
Aged
Middle Aged
*Alzheimer Disease/diagnosis/psychology
Spain
Neuropsychological Tests
Early Diagnosis
Intellectual Disability/psychology
Prodromal Symptoms
Cohort Studies

@article {pmid41453146,
year = {2025},
author = {Camargo, A and Wang, Z},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104151},
doi = {10.1002/alz70856_104151},
pmid = {41453146},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/physiopathology ; Male ; Female ; Magnetic Resonance Imaging ; *Cognitive Dysfunction/diagnostic imaging/physiopathology ; Aged ; Biomarkers ; *Brain/diagnostic imaging/physiopathology ; Brain Mapping/methods ; Middle Aged ; Machine Learning ; },
abstract = {BACKGROUND: Dysconnectivity has been consistently identified in Alzheimer's Disease (AD) through inter-regional correlation analyses, yet cross-time coherence mapping (CTCM) for understanding information exchange remains underexplored. This study utilized resting-state fMRI (rsfMRI) to compute CTCM connectivity (CTCM_conn) and gradient analysis to investigate inter-relationships among 300 brain regions in normal controls (NC), mild cognitive impairment (MCI), and AD groups.

METHOD: Forty NC, 38 MCI, and 40 AD participants were analyzed. Preprocessing steps (motion correction, slice timing correction, normalization, and artifact removal) were performed using SPM12 and FSL. Time series were extracted from 300 Schaefer atlas seeds, and 300×300 CTCM_conn matrices were computed for each subject. Gradients were calculated using the BrainSpace toolbox across four CTCM_conn channels. Population-level mean matrices and gradients were computed for each group, and individual gradients were aligned for comparison. Statistical differences were tested with two-sample t-tests and Bonferroni correction. Machine learning models, incorporating gradients, age, and gender, were evaluated for classifying NC, MCI, and AD, with robustness tested via 1,000 bootstrapped samples.

RESULT: Significant gradient differences were identified: NC vs. MCI: Prominent differences in the visual cortex and Salience/Ventral Attention (SalVentAttn) networks. MCI vs. AD: Differences in the visual, sensorimotor (SomMot), SalVentAttn, Default Mode (Default_PFC and Default_Temp), and dorsal attention (DorsAttn) networks. NC vs. AD: Differences in the SomMot, DorsAttn, Limbic (Limbic_OFC and Limbic_TempPole), and Default_PFC networks. Logistic regression outperformed other models using the original data, and after bootstrapping, most models achieved >90% accuracy.

CONCLUSION: These findings reveal significant alterations in CTCM gradients across NC, MCI, and AD, reflecting the progressive dysconnectivity in AD. Key networks, including the Default Mode, Dorsal Attention, Salience, and Limbic networks, exhibited marked differences. Combining CTCM gradients with demographic features demonstrates strong potential as a biomarker for AD progression and classification, offering new insights for diagnosis and understanding disease mechanisms.},
}

Humans
*Alzheimer Disease/diagnostic imaging/physiopathology
Male
Female
Magnetic Resonance Imaging
*Cognitive Dysfunction/diagnostic imaging/physiopathology
Aged
Biomarkers
*Brain/diagnostic imaging/physiopathology
Brain Mapping/methods
Middle Aged
Machine Learning

@article {pmid41453145,
year = {2025},
author = {Yang, Y and Sathe, A and Schilling, K and Gaynor, LS and Choi, SE and Klinedinst, B and Lee, ML and Trittschuh, EH and Sanders, E and Dumitrescu, L and Landman, BA and Crane, PK and Hohman, TJ and Archer, DB},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104003},
doi = {10.1002/alz70856_104003},
pmid = {41453145},
issn = {1552-5279},
mesh = {Humans ; Genome-Wide Association Study ; Male ; *Alzheimer Disease/genetics/diagnostic imaging ; Female ; Magnetic Resonance Imaging ; Biomarkers ; Aged ; *Brain/diagnostic imaging ; Endophenotypes ; Cross-Sectional Studies ; Longitudinal Studies ; Memory/physiology ; },
abstract = {BACKGROUND: Memory performance is a strong endophenotype for Alzheimer's disease (AD). While the neuroimaging correlates of memory have been explored, their underlying genetic relationship remains unclear.

METHOD: We leveraged GeNetic cOVariance Analyzer (GNOVA) to estimate genetic covariance between two sets of summary statistics from large-scale genome-wide association studies (GWAS). The first was drawn from Elliot et al. (2018)'s GWAS on 3,143 imaging-derived phenotypes (IDP) in 8,428 participants of the UK Biobank; IDPs included 675 diffusion-weighted MRI (dMRI) measures, 675 T1-weighted MRI measures, and 1793 resting-state functional MRI (rs-fMRI) network components derived from group independent component analysis. The second was drawn from a previous GWAS by our group, conducted on memory performance (24,216 participants) and decline (114,070 cognitive sessions) leveraging harmonized cognitive data from 4 longitudinal cohorts of aging: ACT, ADNI, NACC, and ROSMAP. GNOVA was run on cross-sectional memory performance and longitudinal memory decline, with follow-ups conducted after removing APOE region, totaling 4 analyses. GNOVA results were stratified by imaging modality to determine the top IDPs exhibiting greatest genetic covariance with memory performance and decline for dMRI, T1-weighted MRI, and rs-fMRI features, respectively. Percent overlap in volume with Schaefer (2018)'s 7-network atlas was computed for each top rs-fMRI feature.

RESULT: Top dMRI regions exhibiting greatest genetic covariance with memory included the uncinate fasciculus, cingulate gyrus, and superior longitudinal fasciculus (Figure 1). Top T1 regions included posterior collateral sulcus, cuneus gyrus, fusiform gyrus, and anterior middle temporal gyrus (Figure 2). Among top resting-state functional network components, NET25_0067 and NET100_0046 showed considerable overlap with the Default Mode Network (45% and 34%, respectively), whereas NET100_0013 showed large overlap with the Visual Network (52%). An illustration of NET25_0067 is shown in Figure 3.

CONCLUSION: Genetic covariance analyses between memory and multimodal IDPs displayed wide-ranging significant results, with the most pronounced effects centered within medial temporal lobe and adjacent structures. These associations largely parallel AD brain vulnerability, particularly within regions associated with the default mode network. Furthermore, the identification of brain traits beyond the hippocampus as associated with the genetic architecture of memory suggests additional neural correlates to evaluate for future biomarker development.},
}

Humans
Genome-Wide Association Study
Male
*Alzheimer Disease/genetics/diagnostic imaging
Female
Magnetic Resonance Imaging
Biomarkers
Aged
*Brain/diagnostic imaging
Endophenotypes
Cross-Sectional Studies
Longitudinal Studies
Memory/physiology

@article {pmid41453144,
year = {2025},
author = {Eslick, S and Austin, G and Ferguson, J and Oldmeadow, C and Garg, M and Martins, RN},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103690},
doi = {10.1002/alz70856_103690},
pmid = {41453144},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; Male ; Female ; *Amyloid beta-Peptides/blood ; tau Proteins/blood ; Aged ; *Alzheimer Disease/blood ; *Peptide Fragments/blood ; Middle Aged ; Glial Fibrillary Acidic Protein/blood ; *Diet, Vegetarian ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: Research indicates that plant-based diets (PBDs) may be protective against neurodegenerative disease such as Alzheimer's disease. Subsequently, this study examined associations between blood-based AD biomarkers in individuals habitually following different PBDs compared to regular meat-eating diets (RMEs).

METHOD: This study is a secondary analysis of the Plant-based Diets study. Aβ1-42/Aβ1-40, p-tau181, NFL and GFAP were measured in 237 plasma samples via Ultra-sensitive Single Molecule array (SIMOA) from individuals who habitually followed vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or regular meat eater diets. Multivariable regression analyses were undertaken to adjust for age and sex.

RESULT: Plasma Aβ1-42/Aβ1-40 ratio was significantly higher in PVs 0.011 (CI: 0.006, 0.016, p < 0.01), LOVs 0.011 (CI: 0.007, 0.016, p < 0.01) and SVs 0.015 (0.009-0.020, p < 0.01) groups compared to RMEs, following adjustment for age and sex. Plasma p-tau181(pg/mL) was significantly higher in PVs 3.400 (CI: 0.427-6.364, p < 0.05) and LOVs 7.140 (CI: 0.007, 0.016, p < 0.01), NFL (pg/mL) higher in PVs 5.177 (CI: 1.645, 8.710, p < 0.01) and LOVs 4.013 (CI: 1.554, 6.473, p =  0.01), and GFAP (pg/mL) higher in PVs 26.362 (CI: 5.638, 47.086, p < 0.05) and LOVs 20.796 (4.950, 36.643, p =  0.01), all compared to RMEs.

CONCLUSION: Findings suggest that PBDs may be associated with blood-based AD biomarkers, independent of age of sex. Higher plasma levels of Aβ1-42/Aβ1-40 in PBDs compared to RMEs, indicated that PBDs might be associated with lesser amyloid burden. However, higher levels of other plasma AD biomarkers were present in some PBDs compared to RMEs. Future studies should aim to examine associations between specific nutrients and biomarkers of AD to further elucidate the role of diet quality and patterns in AD pathology.},
}

Humans
*Biomarkers/blood
Male
Female
*Amyloid beta-Peptides/blood
tau Proteins/blood
Aged
*Alzheimer Disease/blood
*Peptide Fragments/blood
Middle Aged
Glial Fibrillary Acidic Protein/blood
*Diet, Vegetarian
Neurofilament Proteins/blood

@article {pmid41453142,
year = {2025},
author = {Rani, N and Alm, KH and Callow, DD and Pettigrew, C and Soldan, A and Miller, M and Albert, MSS and Bakker, A and , },
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104629},
doi = {10.1002/alz70856_104629},
pmid = {41453142},
issn = {1552-5279},
mesh = {Humans ; Male ; Positron-Emission Tomography ; Female ; *tau Proteins/metabolism ; *Amyloid beta-Peptides/metabolism ; Aged ; *Cognitive Dysfunction/diagnostic imaging/metabolism ; Biomarkers/metabolism ; *Brain/diagnostic imaging/metabolism/pathology ; *Alzheimer Disease/diagnostic imaging/metabolism ; Aged, 80 and over ; Aniline Compounds ; Cohort Studies ; Middle Aged ; },
abstract = {BACKGROUND: Alzheimer's disease is characterized by accumulation of amyloid-β (Aβ) plaques and tau tangles. Aβ deposition typically begins in neocortical regions years before onset of cognitive decline, while tau pathology spreads systematically through select brain regions, typically described as Braak stages (I-VI). The impact of regional Aβ on tau propagation remains a key research focus.

METHOD: We examined the associations between regional Aβ and tau burden measured by positron emission tomography (PET) in 192 participants without dementia (14 with mild cognitive impairment [MCI]) in the BIOCARD cohort, of whom 52 (27%) were Aβ positive. Amyloid status was assessed using standardized uptake value ratios (SUVR) obtained from the medial orbitofrontal cortex (OFC), lateral OFC, precuneus, posterior cingulate, anterior cingulate, parietal, temporal, and superior frontal regions using 11C-PIB PET. Tau burden was quantified using 18F-MK6240 PET across 29 brain regions, assigned to each of the Braak stages. Associations were examined with stepwise and hierarchical regressions, covarying for age, sex, education, and ApoE4 status.

RESULT: In stepwise regression analyses for Braak stages (I-II), amyloid in the medial OFC emerged as significantly associated with tau burden (β = 1.45, t = 4.75, p <.001 for Braak-I; β = 0.80, t = 3.58, p <.001 for Braak-II), while in later Braak stages, amyloid in the precuneus emerged as significantly associated with tau burden (β = 0.57, t = 9.59, p <.001for Braak-III; β = 1.54, t = 3.76, p <.001 for Braak-IV; β = 0.39, t = 5.90, p <.001 for Braak-V; and β = 0.17, t = 2.30, p <.05 for Braak-VI). Subsequent hierarchical regressions showed that including other Aβ regions did not significantly alter the proportion of variance explained for any Braak stage (Figure 1).

CONCLUSION: Amyloid-tau interactions show regional specificity with medial OFC amyloid burden showing a strong association with early tau pathology accumulation while amyloid in the precuneus is selectively associated with tau in later stages. These findings suggest that localized measures of amyloid burden may enhance early detection and show utility in understanding amyloid-tau dynamics.},
}

Humans
Male
Positron-Emission Tomography
Female
*tau Proteins/metabolism
*Amyloid beta-Peptides/metabolism
Aged
*Cognitive Dysfunction/diagnostic imaging/metabolism
Biomarkers/metabolism
*Brain/diagnostic imaging/metabolism/pathology
*Alzheimer Disease/diagnostic imaging/metabolism
Aged, 80 and over
Aniline Compounds
Cohort Studies
Middle Aged

@article {pmid41453139,
year = {2025},
author = {Kourtis, L},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104638},
doi = {10.1002/alz70856_104638},
pmid = {41453139},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; *Alzheimer Disease/diagnosis/blood ; *Cognitive Dysfunction/diagnosis ; Longitudinal Studies ; Male ; Female ; *Speech/physiology ; Aged ; Neuropsychological Tests ; Australia ; United States ; },
abstract = {BACKGROUND: Blood biomarkers are highly effective in identifying individuals with amyloid pathology, but not all patients with amyloid will go on to develop symptomatic Alzheimer's disease. Prognostic biomarkers are needed to predict who will experience future cognitive decline and are most likely to benefit from early intervention. Speech-derived biomarkers built from acoustic and linguistic features found in speech hold significant potential as scalable prognostic biomarkers working in complement with blood biomarkers and other markers of pathology; however, their development has been hindered by the lack of large, clinically annotated speech datasets needed to train machine learning models.

METHOD: SpeechDx is a longitudinal observational study that collects and harmonizes speech, biomarker, and clinical data from up to 3,000 participants across clinical sites in the U.S., Australia, and Spain. The SpeechDx study population was selected to capture data from participants who may experience stable cognition or cognitive decline during the 3 years of SpeechDx data collection: While participants span the full cognitive spectrum, including normal cognitive (CN), subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer's disease (AD), the majority of the study population is enrolled as CN or SCD. Quarterly, participants remotely complete a brief battery of speech- and language-eliciting tasks via a custom-built SpeechDx app on a study-provided tablet. Tasks are designed to elicit semi-constrained and unconstrained speech, including picture description, story recall, storytelling, and open-ended questions. Concurrently, clinical sites provide participant high-quality clinical and biomarker data collection, including longitudinal blood AD biomarkers, MRI, and neuropsychological assessments. Clinical and biomarker data are paired with individual speech samples, de-identified, and harmonized across all sites to form the unified SpeechDx Dataset. The Dataset is hosted at the AD Data Initiative Workbench, and access is managed by the Data Access Committee.

RESULT: SpeechDx is currently enrolling participants across clinical sites in the US, Australia, and Spain, with interim data release to SpeechDx partners starting in 2025. Full dataset completion is anticipated by the end of 2028.

CONCLUSION: SpeechDx facilitates the development of prognostic AD speech and language biomarkers through the creation of a harmonized database of longitudinal speech, biomarker, and clinical data.},
}

Humans
*Biomarkers/blood
*Alzheimer Disease/diagnosis/blood
*Cognitive Dysfunction/diagnosis
Longitudinal Studies
Male
Female
*Speech/physiology
Aged
Neuropsychological Tests
Australia
United States

@article {pmid41453136,
year = {2025},
author = {Barnwal, M and Baksh, S and Shade, D and Moghekar, A and Rosenberg, PB and Porsteinsson, AP and Lyketsos, KG},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104004},
doi = {10.1002/alz70856_104004},
pmid = {41453136},
issn = {1552-5279},
mesh = {Humans ; Biomarkers/blood ; *Alzheimer Disease/blood/drug therapy/complications ; Amyloid beta-Peptides/blood ; Male ; Female ; tau Proteins/blood ; Aged ; Glial Fibrillary Acidic Protein/blood ; Peptide Fragments/blood ; Neurofilament Proteins/blood ; *Citalopram/therapeutic use ; Aged, 80 and over ; Middle Aged ; },
abstract = {BACKGROUND: Escitalopram for Agitation in Alzheimer's Disease (S-CitAD) was an NIH-funded RCT that randomized 173 participants with Alzheimer's Disease (AD) and agitation to escitalopram or placebo for 12 weeks assessing efficacy for clinically significant agitation. There was no significant advantage for escitalopram in treating agitation. This might be attributed to including participants at various stages of AD brain pathology that would be reflected in levels of blood biomarkers.

METHODS: We examined associations of baseline blood biomarkers and clinical measures at baseline and follow up regarding: (1) agitation severity (NPI-C-A+A); (2) cognitive status, (MMSE); and (3) escitalopram treatment. Abeta42, Abeta40, GFAP, NfL were measured using SIMOA N4PE assays, and pTau217 using the Alzpath-pTau217 SIMOA on Quanterix HD-X.

RESULTS: Abeta40, Abeta42, pTau217, GFAP, and NfL were available for 82 participants. pTau217>0.42 pg/ml and Abeta42/40<0.04 pg/ml indicated significant amyloid pathology. Of 82 participants with pTau217 data, 77 (94%) scored above threshold supporting the clinical diagnosis of AD. In contrast, only 47 were below threshold for Abeta42/40. There was 61% agreement between biomarker cut-offs for pTau217 and Abeta42/40. No baseline associations between biomarkers and NPI-C-A+A scores were significant (p >0.05). Baseline higher pTau217 predicted higher NPI-C-A+A scores at week 6 (beta=3.26, p <0.001) and week 12 (beta=2.86, p = 0.01) after randomization. Baseline associations between Abeta40, Abeta42, NfL and MMSE scores were not significant (p >0.05). However, baseline higher levels of GFAP (beta=-0.02, p = 0.0002) and pTau217 (beta=-2.68, p = 0.003) were associated with lower baseline MMSE scores. Baseline Abeta40, GFAP and NfL were not associated with treatment outcomes. After adjusting for treatment, higher baseline pTau217 was associated with greater odds of worsening NPI-C-A+A scores at weeks 6 (OR=2.79, p = 0.02) and 12 (OR=2.55, p = 0.02) compared to baseline.

CONCLUSION: Baseline blood levels of pTau217 confirmed the presence of significant AD brain amyloid pathology in 94% of participants. Independent of treatment assignment, higher baseline blood levels of pTau217 predicted lower baseline MMSE scores and higher agitation severity at weeks 6 and 12 after randomization.},
}

Humans
Biomarkers/blood
*Alzheimer Disease/blood/drug therapy/complications
Amyloid beta-Peptides/blood
Male
Female
tau Proteins/blood
Aged
Glial Fibrillary Acidic Protein/blood
Peptide Fragments/blood
Neurofilament Proteins/blood
*Citalopram/therapeutic use
Aged, 80 and over
Middle Aged

@article {pmid41453073,
year = {2025},
author = {Giannakopoulou, G and Brown, H and Caponong, F and Vindici, JI and Teoh, S and King, A and Richter, P and Jainis, N and Ibrahim, H},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103681},
doi = {10.1002/alz70856_103681},
pmid = {41453073},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid/diagnosis/diagnostic imaging ; Male ; Female ; Australia ; Amyloid beta-Peptides/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; Hong Kong ; Aged ; *Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging ; Surveys and Questionnaires ; Positron-Emission Tomography ; Middle Aged ; Apolipoprotein E4/genetics ; Risk Assessment ; },
abstract = {BACKGROUND: Biomarker testing and the risk assessment of amyloid-related imaging abnormalities (ARIA) are crucial components in the patient selection and monitoring of disease-modifying therapies (DMTs) for Alzheimer's disease (AD). This study evaluated the adoption of these practices in AD patients in Australia and Hong Kong (HK).

METHODS: A multi-centre online survey of treating neurologists and geriatricians was conducted in Australia (July-September 2024) and HK (November-December 2024). De-identified patient charts were recorded for patients with mild cognitive impairment, mild or moderate AD (suspected or confirmed) seen in the last 3 months. 29 HCPs in Australia and 15 in HK recorded biomarker use, APOE4 status and perceived ARIA risk of 64 and 45 patients, respectively. Recruited HCPs were screened for duration in specialty and caseload. HCP understanding of ARIA in the context of DMTs was collected in HK (small base; qualitative findings).

RESULTS: The use of imaging and CSF biomarkers as diagnostic aids was limited among reported AD patients. In Australia, amyloid-CSF (6.3%), amyloid-PET (1.6%), tau-CSF (3.1%), and tau-PET (0%) tests were rarely conducted. In HK, amyloid-PET was used in 2.2% of patients, with other biomarker PET or CSF tests not performed in any reported cases. Aβ42/40 ratio and p-tau biomarkers were also underutilized. In Australia, these tests were deemed not applicable for 73.4% and 75% of patients, respectively, with the testing status unknown for a further 17.2%. In HK, they were not applicable for 64.4% of reported patients and unknown for 13.3% (Aβ42/40 ratio) and 15.6% (p-tau). APOE4 status was unknown or not tested for all reported patients in Australia and 64.4% in HK. ARIA risk was unknown for 56.3% of patients in Australia, while in HK, 82.2% were cited as "no risk" and 4.4% as unknown. Yet, 73.3% of HK HCPs indicated a basic or limited understanding of ARIA.

CONCLUSION: In this study cohort, biomarker testing, APOE genotyping and ARIA risk assessment were limited among AD patients in Australia and HK, potentially hindering a robust identification of DMT candidates. Future research should investigate the implementation of these practices in larger samples to help advise where further education is needed.},
}

Humans
*Biomarkers/cerebrospinal fluid
*Alzheimer Disease/cerebrospinal fluid/diagnosis/diagnostic imaging
Male
Female
Australia
Amyloid beta-Peptides/cerebrospinal fluid
tau Proteins/cerebrospinal fluid
Hong Kong
Aged
*Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging
Surveys and Questionnaires
Positron-Emission Tomography
Middle Aged
Apolipoprotein E4/genetics
Risk Assessment

@article {pmid41453071,
year = {2025},
author = {Studzinski, C},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106528},
doi = {10.1002/alz70858_106528},
pmid = {41453071},
issn = {1552-5279},
mesh = {Humans ; *Dementia/psychology/therapy/diagnosis ; Cognitive Dysfunction/therapy/psychology/diagnosis ; Ontario ; *Wearable Electronic Devices ; Registries ; },
abstract = {Despite the advancement of wearable technologies, widespread adoption and implementation of these potentially transformative technologies to support aging individuals, including those with mild cognitive impairment (MCI), Alzheimer's disease, and related dementias (ADRD), has yet to be achieved. This barrier to adoption has prevented us from fully realizing the potential transformative impact wearables could have - both in the delivery of compassionate and accessible dementia care and in improving outcomes for aging individuals. This session will share lessons learned from the Ontario Brain Institute's journey to co-design and launch a program called CORTEX (Community-led Real-world neuroTech Experience) that empowers community groups and people with lived experience in testing, implementing, and scaling wearable technology. We will share how the initial concept for CORTEX emerged, how the program was initially co-designed with community groups and people with lived experience, and the learnings from the first pilots conducted in partnership with patient groups. Finally, we will show how the learnings informed the launch of our flagship CORTEX initiative, the Canadian Dementia Registry, which was co-created in partnership with the Alzheimer Society of Ontario. This registry allows us to (1) understand the earliest stage of the dementia journey diagnosis (including how conducting cognitive assessments in the community, on behalf of primary care practitioners fills an early detection gap), (2) test neurotechnologies in diverse populations and compare them to clinically-relevant scales (e.g., MoCA), and (3) look at how these technologies can fit into the care pathway in local communities so that we can increase access to the right clinicians and care they need and deserve.},
}

Humans
*Dementia/psychology/therapy/diagnosis
Cognitive Dysfunction/therapy/psychology/diagnosis
Ontario
*Wearable Electronic Devices
Registries

@article {pmid41453070,
year = {2025},
author = {Strain, JF and Phuah, CL and He, Y and Guo, O and Womack, KB and Gardner, RC and Benzinger, TLS and Schindler, SE and Morris, JC and Bateman, RJ and Barthélemy, NR},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104606},
doi = {10.1002/alz70856_104606},
pmid = {41453070},
issn = {1552-5279},
mesh = {Humans ; *tau Proteins/cerebrospinal fluid ; Male ; Female ; *Biomarkers/cerebrospinal fluid ; *Brain Injuries, Traumatic/cerebrospinal fluid/diagnostic imaging ; Phosphorylation ; Aged ; Middle Aged ; *Alzheimer Disease/cerebrospinal fluid/diagnostic imaging ; Positron-Emission Tomography ; Amyloid beta-Peptides/cerebrospinal fluid ; Brain/diagnostic imaging/metabolism ; },
abstract = {BACKGROUND: Alzheimer Disease (AD) is the most prevalent form of dementia and Traumatic brain injury (TBI) significantly increases the risk of developing dementia. Both AD and TBI are categorized as 3R+4R tauopathies but influence of TBI exposure on AD-like tau phosphorylation in biofluids remains unclear. p-tau217, has gained traction as an early indicator of tau abnormality in response to amyloid deposition in AD. We evaluated whether CSF tau phosphorylation, amyloid deposition, tau aggregation, and neurodegeneration were elevated in cognitively normal individuals with TBI history compared to individuals without TBI.

METHOD: We analyzed CSF p-tau measures in 242 cognitively normal individuals with TBI history quantified with OSU questionnaire. TBI history was ranked by symptom severity: no reported head trauma or TBI (NC), head trauma but no TBI (HT), TBI incident with dazing or confusion for >30 minutes (DZ), and lost consciousness (LOC) for >30 minutes due to the TBI incident. Tau phosphorylation occupancy at T181, T205 and T217 sites was quantified using Mass Spectrometry. PET SUVR summary metrics of amyloid and tau burden were quantified, and summarized neurodegeneration was estimated in AD specific gray matter regions. We constructed statistical linear models based on our primary hypothesis to investigate the relationship between TBI presence/severity at predicting %p-tau217 and other representatives of the ATN framework.

RESULT: This cohort comprised of 52 NC, 42 HT, 23 DZ, and 34 LOC. TBI severity classification did significantly predict pt217 (p = 0.0007) independent of age and sex. Non-parametric tests revealed the LOC group had the greatest %p-tau217 phosphorylation compared to NC (p = 0.0026) and HT (p = 0.011) but not the DZ group (p = 0.15). This effect was not observed for the other tau phosphorylated sites. PET and MRI measures revealed that TBI severity significantly predicted PET amyloid (p = 0.0368) with the LOC group exhibiting the greatest amyloid accumulation. TBI severity did not predict PET tau or neurodegeneration in this asymptomatic cohort.

CONCLUSION: These data demonstrate an association between prior exposure to a severe TBI event with elevated amyloid deposition and selective %p-tau217, suggesting an increasing vulnerability to AD progression, but does not appear to coincide with accelerated neurodegeneration in asymptomatic individuals.},
}

Humans
*tau Proteins/cerebrospinal fluid
Male
Female
*Biomarkers/cerebrospinal fluid
*Brain Injuries, Traumatic/cerebrospinal fluid/diagnostic imaging
Phosphorylation
Aged
Middle Aged
*Alzheimer Disease/cerebrospinal fluid/diagnostic imaging
Positron-Emission Tomography
Amyloid beta-Peptides/cerebrospinal fluid
Brain/diagnostic imaging/metabolism

@article {pmid41453067,
year = {2025},
author = {Raya, MA and Soleimani-Meigooni, DN and Blazhenets, G and Chiotis, K and Lagarde, J and Vrillon, A and Maiti, P and Windon, CC and Zeltzer, E and Zhang, J and Yballa, C and Shankar, R and Amuiri, A and Rocha, S and Hammers, DB and Eloyan, A and Koeppe, RA and Carrillo, MC and Dickerson, BC and Apostolova, LG and Rabinovici, GD and Joie, R},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103476},
doi = {10.1002/alz70856_103476},
pmid = {41453067},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Positron-Emission Tomography ; *Alzheimer Disease/diagnostic imaging/metabolism ; Biomarkers/metabolism ; *Cognitive Dysfunction/diagnostic imaging/metabolism ; tau Proteins/metabolism ; Aged ; Aniline Compounds ; Middle Aged ; Stilbenes ; Carbolines ; *Brain/diagnostic imaging/metabolism ; Cohort Studies ; Amyloid beta-Peptides/metabolism ; },
abstract = {BACKGROUND: The interpretation of an A+T- PET profile in clinically impaired individuals can make it difficult to identify underlying etiology and predict future outcomes. We aimed to assess the frequency of A+T- profiles within a cohort of patients diagnosed with early-onset Alzheimer's Disease and describe their clinical and imaging characteristics.

METHOD: We analyzed 568 LEADS participants with baseline [[18]F]florbetaben and [[18]F]flortaucipir PET: 483 cognitively-impaired (CI, i.e., clinical diagnosis of MCI or dementia) and 85 cognitively unimpaired (CU) participants. Amyloid positivity (A+) was based on [[18]F]florbetaben-PET quantification using a 25 Centiloid threshold. To test the robustness of our findings, tau-PET status was determined in several complementary ways. First, based on an expert visual read following FDA-approved guidelines. Second, based on Flortaucipir-SUVR extracted from various regions of interest (in native space using Freesurfer or in template space with CenTauR procedures) and thresholded using different statistical methods (Table 1). We then compared baseline characteristics between the A+T- and A+T+ groups using Kruskall-Wallis or Fisher exact tests and assessed differences in longitudinal clinical decline using linear mixed effect models (outcome: CDR-SB).

RESULT: Among 364 A+ CI participants, rates of negative tau-PET were minimal (3-7%), regardless of the tau-PET approach (Table 1). Visual reads were highly concordant with tau status defined by quantitative approaches (agreement=96-99%, Kappa=0.48-0.84). Comparison between the A+T+ and A+T- groups was performed twice, based on the two methods that provided the divergent T- rates: visual reads (4%) or global cortical SUVR with a Gaussian Mixture Model-based threshold (7%). Regardless of the tau status definitions, the A+T- group exhibited milder clinical impairment than the A+T+ group despite being older and having a higher frequency of APOE-e4, hypercholesterolemia, and tobacco smoking (Table 2). The A+T- group had lower amyloid burden and larger hippocampal volumes than A+T+ patients but similar white matter hyperintensity burden. Longitudinally, the A+T- group showed a significant increase in CDR-SB, but clinical progression was slower than the A+T+ group (Figure 1).

CONCLUSION: In amyloid-positive patients with EOAD, tau-PET results were predominantly positive regardless of tau-status definitions (93-97%). The rare A+T- profile may reflect early disease stages, with tau pathology below PET detection levels.},
}

Humans
Female
Male
Positron-Emission Tomography
*Alzheimer Disease/diagnostic imaging/metabolism
Biomarkers/metabolism
*Cognitive Dysfunction/diagnostic imaging/metabolism
tau Proteins/metabolism
Aged
Aniline Compounds
Middle Aged
Stilbenes
Carbolines
*Brain/diagnostic imaging/metabolism
Cohort Studies
Amyloid beta-Peptides/metabolism

@article {pmid41453052,
year = {2025},
author = {Nallapu, BT and Rabin, LA and Lipton, RB and Ezzati, A},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e105375},
doi = {10.1002/alz70858_105375},
pmid = {41453052},
issn = {1552-5279},
mesh = {Humans ; *Dementia/psychology/diagnosis ; *Neuropsychological Tests ; },
abstract = {BACKGROUND: Comprehensive neuropsychological assessments are essential for characterizing cognitive deficits in Alzheimer's Disease and related dementias (ADRD), providing essential data for modeling disease progression and heterogeneity. However, the availability of multiple versions of similar tests, variations in language translations, and the existence of localized normative data make selecting and interpreting these assessments challenging for researchers, especially when working with demographically diverse individuals. Current resources, such as review articles and expert guidance, are limited in scope and accessibility, leaving gaps in knowledge and usability.

METHOD: To address these gaps, we developed a centralized, open-source repository of neuropsychological instruments that enables users to search for tests using various criteria, including name, geographic region, population of interest, and language. For each test, the repository provides comprehensive, curated information on its purpose, subcomponents, and cognitive domains assessed. The outcomes include metadata on source of the information, availability of local norms, language versions, and alternate test forms. For instruments not available in the repository, large language models (LLMs) generate preliminary summaries from existing literature, which can be submitted for expert review and refinement (Figure 1). The repository also supports crowdsourcing and community contributions to enrich the repository by incorporating information about original publications, translations, and test modifications.

RESULT: The repository, named CogIns (Cognitive Instruments), is freely accessible at https://cogins.github.io and continues to expand daily. Details of several cognitive instruments are available with appropriate tags of AI Generated or Under Review (Figure 2). Preliminary user feedback highlights the tool's ability to streamline the knowledge organization related to the cognitive instruments and improve research accessibility, particularly for interdisciplinary researchers starting in the field of ADRD and those working with underrepresented populations.

CONCLUSION: This repository represents a significant advance in democratizing access to neuropsychological assessment tools in ADRD research. It not only simplifies the process of identifying suitable tests but also establishes a scalable model forcommunity-driven knowledge dissemination. Future updates aim to expand the repository's coverage, onboard experts to validate and curate the community-generated information and introduce enhancements such as recommendations for relevant research, support for alternative languages, and access to publicly available test versions.},
}

Humans
*Dementia/psychology/diagnosis
*Neuropsychological Tests

@article {pmid41453043,
year = {2025},
author = {Yang, I and Hendler, K and Scannapieco, FA and Boykins, G and Wharton, W},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103436},
doi = {10.1002/alz70856_103436},
pmid = {41453043},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; Female ; Male ; *Alzheimer Disease/cerebrospinal fluid ; Middle Aged ; *Microbiota ; *Periodontal Diseases/microbiology ; *Social Determinants of Health ; Aged ; Inflammation ; },
abstract = {BACKGROUND: Evidence suggest an association between periodontal disease (PerioD) and Alzheimer's disease (AD), with PerioD-associated microbial ecosystems driving oral and systemic inflammation that may activate or accelerate neuroinflammation, a hallmark of AD. Social determinants of health (SDoH) are critical factors influencing both oral health and AD risk yet are often overlooked, and rarely investigated together. This study aims to characterize and compare the oral microbiome of age- and education-matched individuals at high risk for AD by virtue of family history, with and without PerioD, and to investigate the relationships between PerioD-associated microbiome features, SDoH, systemic inflammation and brain inflammation, and AD biomarkers (in cerebrospinal fluid [CSF]).

METHOD: This two-year NINDS-funded study collects oral microbiome samples, blood, and CSF annually in a cognitively normal, racially diverse cohort (n = 165). Metagenomic sequencing will be used to investigate cross-kingdom microbial communities and their association with inflammatory and systemic markers. Surveys and interviews investigate behaviors and SDoH influencing PerioD and AD risk.

RESULT: To date, 55 participants have been recruited. Participants are 62 years of age on average, predominantly white (70%), female (63.3%), with Stage 1-2 periodontitis (85.7%). Preliminary analyses found no significant relationships between bleeding on probing, behavioral factors, SDoH variables, and Montreal Cognitive Assessment (MoCA) scores, which was expected given the small sample size. As recruitment continues, we anticipate identifying associations between oral microbiome features, inflammatory markers, AD biomarkers and cognitive outcomes. SDoH, such as access to dental care and oral hygiene behaviors, may mediate these relationships, offering insights into the interplay between periodontal disease, systemic inflammation, and AD risk.

CONCLUSION: By leveraging longitudinal data and exploring upstream sociocultural factors, this research addresses critical gaps in understanding PerioD's contribution to AD risk. Findings will provide novel insights into the interplay between the oral microbiome, systemic inflammation, brain inflammation, and AD risk.},
}

Humans
*Biomarkers/cerebrospinal fluid
Female
Male
*Alzheimer Disease/cerebrospinal fluid
Middle Aged
*Microbiota
*Periodontal Diseases/microbiology
*Social Determinants of Health
Aged
Inflammation

@article {pmid41453032,
year = {2025},
author = {Ray, K and Barbakova, O},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106140},
doi = {10.1002/alz70858_106140},
pmid = {41453032},
issn = {1552-5279},
mesh = {Humans ; *Dementia/psychology ; Female ; Male ; Aged ; *Art ; Aged, 80 and over ; Nursing Homes ; },
abstract = {BACKGROUND: Art has been increasingly recognized as a valuable tool in enhancing the well-being of individuals in memory care settings. Research indicates that engaging in creative activities can significantly benefit residents with Alzheimer's disease or related dementia (ADRD) by stimulating cognitive functions, fostering social connections, and providing avenues for self-expression. This community-based art project was designed to explore these benefits within a skilled nursing facility, where residents could collaboratively create artwork that honors their past experiences and memories.

METHOD: Over several weeks, a group of memory care residents (n = 6) at a skilled nursing facility participated in creating a piece of art titled "Nature and People: A Beautiul Mynd." This collaborative effort involved utilizing various objects from nature including dried fruit, flowers and leaves. The process encouraged residents to tap into their long-term memories and express themselves through the creation of nurturing and meaningful artwork.

RESULT: A Beautiful Mynd, Memorializing Yesterdays Nurturing Dreams culminated into a visually stunning piece. The artwork is a vibrant representation of the residents' memories and experiences, as it integrates elements from nature that evoke emotional connections and reminiscence. By working together, the residents not only fostered a sense of community but also created lasting expressions of their collective memories.

CONCLUSION: Through this project, we highlight the significant impact that community-based art initiatives can have on enriching the lives of residents with dementia, fostering both creativity and connection.},
}

Humans
*Dementia/psychology
Female
Male
Aged
*Art
Aged, 80 and over
Nursing Homes

@article {pmid41453029,
year = {2025},
author = {Cogswell, PM and Preboske, GM and Klein, G and Benzinger, TLS and Bateman, RJ and Jack, CR and , },
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103166},
doi = {10.1002/alz70856_103166},
pmid = {41453029},
issn = {1552-5279},
mesh = {Humans ; Magnetic Resonance Imaging ; *Alzheimer Disease/diagnostic imaging/drug therapy ; Biomarkers ; Male ; Female ; *Brain/diagnostic imaging/pathology ; Middle Aged ; Aged ; *Cerebral Hemorrhage/diagnostic imaging ; },
abstract = {BACKGROUND: Amyloid-Related Imaging Abnormalities (ARIA), an adverse event associated with Alzheimer's disease anti-amyloid immunotherapies, occur in the form of edema or sulcal effusion (ARIA-E) and microhemorrhages and superficial siderosis (ARIA-H). Conventional teaching is that ARIA-H is permanent hemosiderin staining of the brain. In clinical trials we have noticed that some ARIA-H microhemorrhages that occur with regional ARIA-E appear to later resolve. The goal of this study is to illustrate that, opposed to current understanding, some ARIA-H microhemorrhages may resolve.

METHODS: We identified participants from the Dominantly Inherited Alzheimer's Network Trial Unit (DIAN-TU) and open label extension (OLE) gantenerumab studies that had ARIA-E and at least one ARIA-H microhemorrhage. The T2* GRE sequence from all available MRI exams in a patient were co-registered and reviewed by a board-certified neuroradiologist. Individual microhemorrhages were tracked over the serial exams. We defined disappearing/resolving microhemorrhages as those appeared with or following ARIA-E, were visualized on at least 2 MRI exams, and were subsequently not visualized on at least 2 MRI exams.

RESULTS: A total of 12 patients met inclusion criteria of which 5 (41%) had microhemorrhages that resolved over 10-40 months follow-up after the incident ARIA. These microhemorrhages occurred in clusters in the region of ARIA-E, and only some of the regional microhemorrhages resolved over follow-up. Examples are shown in Figures 1-3.

CONCLUSIONS: The disappearance (resolution) of ARIA-H microhemorrhages is relevant to the management and continued dosing of patients receiving anti-amyloid immunotherapies as this is guided by the presence of ARIA (including cumulative treatment emergent microhemorrhages) as well as clinical symptoms. A microhemorrhage number alone may not be indicative of the potentially dynamic nature of ARIA-H.},
}

Humans
Magnetic Resonance Imaging
*Alzheimer Disease/diagnostic imaging/drug therapy
Biomarkers
Male
Female
*Brain/diagnostic imaging/pathology
Middle Aged
Aged
*Cerebral Hemorrhage/diagnostic imaging

@article {pmid41453027,
year = {2025},
author = {Rizzo, M and Teunissen, CE and Brosseron, F and Kuhs, S and Kollmorgen, G and Zetterberg, H and Blennow, K and Krüger, R and Fernandes, SBG and Aarsland, D and Borejko, O and Chokoshvili, D and van der Flier, WM and Lemstra, AW and Tijms, BM and Petzold, GC and Spottke, A and Frisoni, GB and Brockmann, K and Gasser, T and Fladby, T and Wettergreen, M and Jessen, F and Düzel, E and Höglinger, GU and Chevalier, C and Krishnan, R and Visser, PJ and Vos, SJB and , },
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104363},
doi = {10.1002/alz70856_104363},
pmid = {41453027},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Biomarkers/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid ; Aged ; Amyloid beta-Peptides/cerebrospinal fluid ; *Parkinson Disease/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; alpha-Synuclein/cerebrospinal fluid ; *Lewy Body Disease/cerebrospinal fluid ; Peptide Fragments/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; Aged, 80 and over ; Middle Aged ; *Complement System Proteins/cerebrospinal fluid ; },
abstract = {BACKGROUND: While evidence suggests complement system involvement in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), its association with disease biomarkers remains unclear. We investigated the relationship of complement factors with amyloid, tau, NfL, and α-synuclein in CSF in AD, DLB, PD, and controls.

METHOD: We included 321 individuals with AD, DLB, PD, and controls from 6 centers of the EPND study. CSF Aβ42/40, p-tau181, NfL, and α-syn were centrally measured using NeuroToolKit (Roche Diagnostics), and 14 CSF complement factors using Milliplex (Merck KGaA). Controls were defined as normal cognition and normal Aβ42/40, whereas AD as abnormal Aβ42/40 without meeting clinical criteria of DLB or PD. Linear regression models adjusted for age and sex were used. Associations were post-hoc compared between individuals with low(≤23), intermediate(24-27), and high(≥28) MMSE scores.

RESULT: Sample characteristics are presented in Table 1. Lower Aβ42/40 levels were associated with lower levels of 7 complement factors in controls and with higher C1q and C2 levels specifically in AD (Figure 1, Figure 2). No associations of Aβ42/40 with complement were found in DLB and PD. Higher p-tau181 levels were associated with increased levels of 7 complement factors in controls and 6 in AD, and showed fewer associations in DLB and PD. The strength of p-tau181 associations with complement was similar across groups. Higher NfL levels were widely associated with higher complement factor levels in controls (13) and AD (12), and less in PD (6) and DLB (4). Higher α-syn levels were broadly associated with higher complement factor levels in AD (13), controls (12), and DLB (12), but only minimally in PD (1). The strength of these NfL and α-syn associations with complement was not disease-specific. Conversely, compared to all groups, in PD higher α-syn levels were associated with lower C5, C5a, C9, factor-I and properdin levels. Individuals with intermediate MMSE scores largely drove the associations of α-syn with complement in AD. MMSE level did not clearly impact other associations.

CONCLUSION: CSF complement factors were associated with amyloid, tau, NfL, and α-synuclein, suggesting complement system involvement in several neurodegenerative diseases. Complement showed disease-specific associations with amyloid in AD and α-synuclein in PD.},
}

Humans
Female
Male
Biomarkers/cerebrospinal fluid
*Alzheimer Disease/cerebrospinal fluid
Aged
Amyloid beta-Peptides/cerebrospinal fluid
*Parkinson Disease/cerebrospinal fluid
tau Proteins/cerebrospinal fluid
alpha-Synuclein/cerebrospinal fluid
*Lewy Body Disease/cerebrospinal fluid
Peptide Fragments/cerebrospinal fluid
Neurofilament Proteins/cerebrospinal fluid
Aged, 80 and over
Middle Aged
*Complement System Proteins/cerebrospinal fluid

@article {pmid41453024,
year = {2025},
author = {Wu, SA and Morrison, A and Oliveira, CC and Randa-Beaulieu, C and Cooke, HA},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106050},
doi = {10.1002/alz70858_106050},
pmid = {41453024},
issn = {1552-5279},
mesh = {Humans ; *Dementia/psychology/therapy ; Focus Groups ; Female ; Male ; Ontario ; Aged ; British Columbia ; *Caregivers/psychology ; Middle Aged ; },
abstract = {BACKGROUND: Discourse on disease-modifying treatments (DMTs) for dementia has primarily focused on drug development, health system readiness and health care professional perspectives. There is a paucity of research focused on public perceptions held by Canadians towards these treatments. Focus groups were conducted in British Columbia and Ontario, Canada with people affected by dementia to gain an in-depth understanding of their experiences with and perceptions of DMTs.

METHOD: Between February and December 2024, the Alzheimer Society of B.C. (ASBC) and the Alzheimer Society of Ontario (ASO) held a series of separate focus groups. ASBC conducted four online focus groups with eight persons living with dementia and nine care partners, none of whom were enrolled in DMT clinical trials. ASO conducted three in-person and two online focus groups with people living with dementia (n = 12) and their care partners (n = 11) enrolled in DMT clinical trials. Focus groups ranged from 90-120 minutes and consisted of questions exploring treatments, risk tolerance and the role of our organizations to support patient navigation for DMTs. Data were analyzed using thematic analysis.

RESULT: Focus group participant experiences ranged depending on disease progression. Four themes were identified. The first, equitable access to DMTs, highlighted concerns around financial hardship, geographic limitations and the critical importance of care partner support. The second, risk tolerance, underscored differences in risk acceptance among people living with dementia and their care partners, and the variation across disease stage. The third, clear and accessible information, focused on the need for comprehensive, transparent and easy-to-understand material to ensure informed DMT decision-making. The final theme, DMTs as a source of hope, acknowledged the motivational role of clinical trials and DMT approvals symbolizing innovation and the potential for an eventual cure. ASBC and ASO were identified as trustworthy and important sources of support for DMT navigation.

CONCLUSION: Findings identify priority areas for people affected by dementia once DMTs become available in Canada. Collaborating with people with lived experience in the development of DMT care pathways will help to ensure that treatment options are accessible, deliver meaningful benefits to extend quality of life and improve quality of care.},
}

Humans
*Dementia/psychology/therapy
Focus Groups
Female
Male
Ontario
Aged
British Columbia
*Caregivers/psychology
Middle Aged

@article {pmid41453022,
year = {2025},
author = {Pollard, C},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103924},
doi = {10.1002/alz70856_103924},
pmid = {41453022},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; *Alzheimer Disease/diagnosis/genetics/blood ; DNA Methylation ; Parkinson Disease/diagnosis/genetics/blood ; *Cognitive Dysfunction/diagnosis/blood/genetics ; Male ; Female ; Dopaminergic Neurons/metabolism ; Aged ; *Cell-Free Nucleic Acids/blood ; Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Nanopore Sequencing ; },
abstract = {BACKGROUND: Current diagnostic standards for Alzheimer's disease (AD), amyloid and tau biomarkers, provide valuable insights but are limited as early screening tools and lack applicability across neurodegenerative conditions. Our preliminary findings show cortical neuron-derived cell-free DNA (cfDNA) in blood correlates with mild cognitive impairment (MCI) and AD, offering a neuron-specific measure of neurodegeneration[1]. However, this cfDNA detection relied on bisulfite sequencing at a single cortical neuron-specific site, constrained by DNA damage, PCR biases, and limited scope. We present a nanopore sequencing approach that eliminates these limitations, enabling analysis of thousands of cell type-specific loci with superior sensitivity and accuracy. This approach is also applied to dopaminergic neurons in Parkinson's disease (PD) and spinal motor neurons in amyotrophic lateral sclerosis (ALS), positioning cfDNA as a promising target for early detection, staging, and management of neurodegenerative diseases.

METHODS: DNA was extracted from blood plasma and cortical, spinal motor, and dopaminergic neurons. Whole-genome sequencing was performed using nanopore technology (PromethION, Oxford Nanopore Technologies) to enable native DNA methylation analysis without bisulfite conversion or amplification. Neuron-specific methylation signatures were identified across the genome, targeting differentially methylated regions (DMRs) unique to each cell type. cfDNA from blood samples of controls and patients with MCI/AD (n = 80), PD (n = 64), and ALS (n = 70) was sequenced and analyzed at neuron-specific loci.

RESULTS: Mixed DNA dilutions demonstrated >96% accuracy in assigning cortical, dopaminergic, and spinal motor neurons, targeting 4,152,224 loci for cortical neurons, 130,137 loci for dopaminergic neurons, and 1,427,252 loci for spinal motor neurons. cfDNA levels were significantly elevated in MCI/AD (p = 2.2e-6), PD (p = 1.014e-14), and ALS (p = 2.056e-14).

CONCLUSION: Nanopore sequencing achieves accurate neuron-specific cfDNA methylation analysis and demonstrates potential as a minimally invasive target for early detection, staging, and monitoring of neurodegenerative diseases. A longitudinal AD validation study (n = 775) is underway in collaboration with the University of Kansas Alzheimer's Disease Research Center to assess early screening and disease monitoring applications in AD. References 1. Pollard, et al. Detection of neuron-derived cfDNA in blood plasma: a new diagnostic approach for neurodegenerative conditions. Frontiers in Neurology. 2023.},
}

Humans
*Biomarkers/blood
*Alzheimer Disease/diagnosis/genetics/blood
DNA Methylation
Parkinson Disease/diagnosis/genetics/blood
*Cognitive Dysfunction/diagnosis/blood/genetics
Male
Female
Dopaminergic Neurons/metabolism
Aged
*Cell-Free Nucleic Acids/blood
Amyotrophic Lateral Sclerosis/diagnosis/genetics
Nanopore Sequencing

@article {pmid41453021,
year = {2025},
author = {Mammel, A and Hsiung, GR and Mousavi, A and Kumar, P and Hallett, K and MacKenzie, IR and Hirsch-Reinshagen, V and Biehl, D and Gil, P and Encarnacion, M and Frykman, H},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103744},
doi = {10.1002/alz70856_103744},
pmid = {41453021},
issn = {1552-5279},
mesh = {Humans ; *tau Proteins/blood ; *Alzheimer Disease/blood/diagnosis/pathology ; *Biomarkers/blood ; Female ; Male ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Lewy Body Disease/blood/diagnosis/pathology ; Phosphorylation ; },
abstract = {BACKGROUND: Blood-based biomarkers provide an accessible and cost-effective tool for diagnosing Alzheimer's disease (AD). Among these biomarkers, phosphorylated tau 217 (p-tau217) shows promise for AD diagnosis, differential diagnosis, and facilitating access to emerging disease-modifying therapies. This study evaluates the ALZpath plasma p-tau217 assay as a Laboratory Developed Test for distinguishing AD pathology from other concurrent pathologies associated with AD.

METHOD: We examined EDTA plasma samples of autopsy confirmed (n = 110) of patients assessed at the UBC Hospital Clinic for Alzheimer's disease. The cohort was characterized as AD only (n = 30), AD with CAA (n = 7), AD with DLB (n = 13), AD with Vascular (n = 7), AD with mix pathologies (n =  13), TDP-43 only (n =  18), Synuclein only(n = 4), Tau only (n = 18). The samples were analyzed by the ALZpath p-tau217 v2 assay on a single Quanterix HD-X SIMOA Analyzer platform.

RESULTS: While the plasma p-tau217 concentrations in cases with AD (1.6 ± 0.8 ng/L) were higher than those in AD with DLB cases (1.1 ± 0.7 ng/L) and cases with AD plus vascular pathology (1.0 ± 0.6 ng/L), and lower than in cases with AD plus CAA (1.7 ± 0.6 ng/L), these differences were not statistically significant. However, the concentrations were significantly higher than those in cases with AD with mixed pathologies (0.7 ± 0.4 ng/L), TDP-43 only (0.3 ± 0.2 ng/L), synuclein only (0.4 ± 0.1 ng/L), and tau only (0.3 ± 0.2 ng/L) (p < 0.001).

CONCLUSION: In our current study, plasma p-tau217 levels did not differentiate AD with DLB, AD with vascular pathology, or AD with CAA cases from the AD group, though they could differentiate AD from cases with mixed pathologies, TDP-43 only, synuclein only, and tau-only pathology. This suggests co-existing AD pathology, making their p-tau measurements similar to the AD group. Further studies with autopsy-defined samples will be needed to clarify the role of plasma p-tau217 in these groups.},
}

Humans
*tau Proteins/blood
*Alzheimer Disease/blood/diagnosis/pathology
*Biomarkers/blood
Female
Male
Aged
Aged, 80 and over
Diagnosis, Differential
Lewy Body Disease/blood/diagnosis/pathology
Phosphorylation

@article {pmid41453020,
year = {2025},
author = {Hoang, B and Pang, Y and Liang, S and Dodge, HH and Zhou, J},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103800},
doi = {10.1002/alz70856_103800},
pmid = {41453020},
issn = {1552-5279},
mesh = {Humans ; *Cognitive Dysfunction/diagnosis ; *Biomarkers ; Male ; Female ; Aged ; Alzheimer Disease/diagnosis ; *Language ; },
abstract = {BACKGROUND: Mild Cognitive Impairment (MCI) is the prodromal stage of Alzheimer's disease. Early detection of MCI is essential for effective intervention and treatment. Recent studies have shown that linguistic marker is a promising and cost-effective approach to identify MCI. Existing studies aggregated multiple rounds of conversation and demonstrated their effectiveness, and yet the use of finer granularity of conversation is not widely studied. Intuitively, the time series of language markers reveal important dynamics that are easily wiped off by aggregation. Significant individual differences in speaking styles pose challenges for sequence models in capturing cognitive characteristics. We propose a novel temporal harmonization method that mitigates distributional differences in temporal language markers across subjects, enhancing the prediction.

METHOD: We utilized 6,771 conversations from 74 participants in Internet-Based Conversational Engagement Clinical Trial (I-CONECT) (NCT02871921). From each 30-minute conversation session, we extracted a 99-dimensional feature set including Linguistic Inquiry and Word Count, Syntactic Complexity, Lexical Diversity, and Response Length. For each subject, we have a sequence of feature vectors over time, up to 12 months. Our harmonization method leverages adversarial training via a min-max optimization framework with three components: Seq2Seq Harmonization, a Subject Classifier, and a Cognitive Classifier. The harmonization module learns to remove subject-specific components from temporal linguistic features, while the Subject Classifier infers subject identity. Finally, the Cognitive Classifier focuses on detecting MCI from the harmonized temporal features.

RESULT: We compared our approach with single-conversation input methods, where we trained neural networks to predict the outcome of individual conversations and used majority voting to determine the final output for each participant. Our results show that using temporal sequences improves detection performance compared to aggregated single-conversation outputs, both with and without harmonization. When applying temporal harmonization, the performance of subject classification significantly increases, achieving an AUC of 0.720 compared to 0.647 without harmonization.

CONCLUSION: Using only features extracted from semi-structured conversation, we achieved a reasonalbe AUC. Our study demonstrates the additional benefits of using temporal sequences of language markers to detect Mild Cognitive Impairment. Moreover, applying temporal harmonization helps remove subject-specific components in features and further enhances cognitive detection performance.},
}

Humans
*Cognitive Dysfunction/diagnosis
*Biomarkers
Male
Female
Aged
Alzheimer Disease/diagnosis
*Language

@article {pmid41453013,
year = {2025},
author = {Ding, H and Serrano, X and Searls, E and Ho, K and Li, Z and Burk, A and Low, M and Lyu, C and Gifford, KA and Kolachalama, VB and Lin, H and Nowinski, CJ and Palmisano, JN and Tripodis, Y and Turk, KW and Budson, AE and McKee, AC and Mez, J and Au, R and Alosco, ML},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103876},
doi = {10.1002/alz70856_103876},
pmid = {41453013},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; *Neuropsychological Tests/statistics & numerical data ; Pilot Projects ; *Biomarkers ; *Cognitive Dysfunction/diagnosis ; },
abstract = {BACKGROUND: Exposure to repetitive head impacts (RHI) from contact and collision sports, military service, and other sources have been linked to cognitive decline and neurodegenerative disorders. Traditional neuropsychological measures often miss the subtle cognitive deficits that can occur in individuals exposed to RHI. Digital measures might be more sensitive alternatives. However, little is known about how RHI influences the stability of digital neuropsychological measures in cognitively intact older adults.

METHOD: This pilot study analyzed data from participants enrolled in the Boston University Alzheimer's Disease Research Center. RHI status is based on the 2021 NINDS TES Research Diagnostic Criteria. Participants complete annual study visits that includes Uniform Data Set. In 2021, Defense Automated Neurobehavioral Assessment (DANA) was introduced. The sample included cognitively intact older adults with at least three days of engagement with DANA. Intraindividual variability was quantified using the coefficient of variation (CV), and Mann-Whitney U tests compared CVs between RHI and non-RHI groups. Day-to-day variations and group differences were further examined with a linear mixed-effects model, adjusting for age, sex, the number of usage days and RHI group, plus their interaction term.

RESULT: This study included 58 participants (mean age: 75.4±9.3 years; 67.2% women; mean education: 17±2 years; 93.1% White) (Table 1). Of these, 10 were RHI, with soccer as the primary sport for 4, football for 2, rugby for 1, and other sports for 3. Overall, day-to-day fluctuations in DANA performance were small, yet individuals with RHI showed significantly greater variability across some tasks (e.g., Go/No-Go, Code Substitution, Simple Response Time) than those without RHI (Table 2). Notably, in the Procedural Response Time task, each additional day of DANA usage was significantly associated with a 21.6 ms faster average response time for all test trials (P = 0.007). However, a significant interaction effect (beta = 38, P = 0.012) was observed for the RHI group.

CONCLUSION: Although digital measures were generally stable across days, older adults with RHI exhibited more pronounced variability and appeared to benefit less from repeated practice. These findings underscore the need to consider RHI history when interpreting longitudinal cognitive assessments in aging populations.},
}

Humans
Male
Female
Aged
*Neuropsychological Tests/statistics & numerical data
Pilot Projects
*Biomarkers
*Cognitive Dysfunction/diagnosis

@article {pmid41453007,
year = {2025},
author = {Aponte, C and García, L and Ramírez, MJH and Zea, L and Quintero, CAT and Gómez, JFO and Niño, DFA},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104007},
doi = {10.1002/alz70856_104007},
pmid = {41453007},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Magnetic Resonance Imaging ; *Alzheimer Disease/genetics/diagnostic imaging/physiopathology ; Middle Aged ; Biomarkers ; Presenilin-1/genetics ; *Brain/diagnostic imaging/physiopathology ; Mutation/genetics ; Aged ; Cognitive Dysfunction ; },
abstract = {BACKGROUND: Graph metrics have been used to evaluate functional connectivity in Alzheimer's disease (AD). It has been found that nodal and global graph metrics are altered in subjects with AD and MCI compared to controls. In subjects with mutations associated with autosomal dominant Alzheimer's disease (ADAD), these metrics may vary depending on the stage within the disease continuum. This study aimed to evaluate the characteristics of graph metrics in the DMN specifically in asymptomatic subjects carrying the PSEN1 E280A mutation.

METHODS: 32 asymptomatic carriers (aC) and 25 non-carrier controls (nC) matched by sex, age and education status, underwent rs-fMRI acquisition for 10 minutes. Pre-processing of images was performed with CONN toolbox and RSN were extracted with Schaefer atlas with 79 ROI for DMN. Graph metrics were extracted with GRETNA toolbox, with a range of sparsity thresholds from 0.05-0.5 for all metrics. A non parametric t-test wilcoxon and linear mixed model (LMM) were performed, with corrections for multiple comparisons with Bonferroni.

RESULTS: Significant differences were found in education (p-value < 0.001, confidence interval 95% 1.43 - 5.15), but not for age and sex. Betwenness Centrality (Bc) was higher in nC tan aC (p-value 0.0051, Cohen's d estimate: -0.011 CI95% -0.030 to 0.007) and Modularity (Q) (p-value 0.042, Cohen's d estimate: -0.15 CI95% -0.318 to 0.0136). Regarding the LMM, differences were observed in the intercepts of nodal graph metrics, but no differences were found between groups. However, when examining each intercept individually, it was shown that clustering coefficient, betweenness centrality, local efficiency, and degree centrality increase the slope in nC, while they decrease it in aC. At the global graph level, no differences were found between aC and nC groups.

CONCLUSION: Bc idifferentiates between aC and nC. It is higher in nC, indicating that, at a local level, there is a greater number of nodes through which more connections pass, making them central to DMN connectivity. The local changes in aC are attributed to pathophysiological alterations in information distribution and the reorganization of DMN to distribute information across RSN and preserve cognitive functions.},
}

Humans
Male
Female
Magnetic Resonance Imaging
*Alzheimer Disease/genetics/diagnostic imaging/physiopathology
Middle Aged
Biomarkers
Presenilin-1/genetics
*Brain/diagnostic imaging/physiopathology
Mutation/genetics
Aged
Cognitive Dysfunction

@article {pmid41453005,
year = {2025},
author = {Shah, S and Wadhwa, SS and Huerta, GI and Eliseo, SGO and Martinez, A and Campos, B and Vossel, K and Bholat, M and Diaz-Santos, M and Chang, TS},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e105676},
doi = {10.1002/alz70858_105676},
pmid = {41453005},
issn = {1552-5279},
mesh = {Humans ; Male ; Aged ; Female ; *Dementia/diagnosis/psychology/therapy ; Aged, 80 and over ; Surveys and Questionnaires ; Mental Status and Dementia Tests ; Middle Aged ; Electronic Health Records ; *Alzheimer Disease/diagnosis/psychology ; *Mass Screening/methods ; Los Angeles ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) affects over 10% of individuals aged 65 and older, with Black and Hispanic/Latino individuals experiencing a 1.5-2.0 times higher prevalence than white individuals. Despite these disparities, AD remains underdiagnosed, particularly in non-white populations. Current dementia screening tools, such as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), face challenges in time efficiency, accessibility, and cultural sensitivity. This study aimed to implement a brief dementia screening tool integrated into the electronic health record (EHR) and evaluate its impact on diagnosis, workup, and treatment in a diverse family medicine clinic in Los Angeles County.

METHOD: The dementia screening tool (DST), developed collaboratively by the University of California Alzheimer's Disease Centers and the California Department of Public Health, was designed to be brief (<5 minutes) and adaptable. It includes a three-question patient questionnaire, an informant input option, and the Mini-Cog assessment. To enhance accessibility, the tool was translated and culturally adapted for Spanish-speaking patients. Patients aged 60+ completed the DST before their annual wellness visits, with results integrated into the EHR. This pre-post intervention study compared patients aged 60+ without a prior dementia diagnosis during the pre-intervention (February 2016-August 2022) and post-intervention (September 2022-June 2023) periods. Outcomes included new dementia diagnoses, medications, specialty referrals, labs, and imaging.

RESULT: The DST was implemented, screening 996 patients in 10 months. Screening led to 35 specialty care referrals and 15 new dementia diagnoses. New diagnoses increased from 4.17% pre-DST to 4.80% post-DST all (OR 2.10, p = 0.02) and 6.43% among those screening positive (OR 2.57, p = 0.04). Dementia medication prescriptions rose from 2.93% pre-DST to 4.94% in the post-DST all group, reaching 6.87% among those who screened positive. Specialty referrals were more frequent post-DST all (9.13%) and even higher among those screening positive (14.16%). Post-DST, all secondary outcomes significantly improved, including increased use of diagnostic labs and imaging studies.

CONCLUSION: Integrating a brief, culturally sensitive DST into primary care significantly improved dementia diagnosis rates, workup, referrals, and treatment. These findings highlight the potential for broader implementation of the DST to enhance dementia care and address health disparities in diverse populations.},
}

Humans
Male
Aged
Female
*Dementia/diagnosis/psychology/therapy
Aged, 80 and over
Surveys and Questionnaires
Mental Status and Dementia Tests
Middle Aged
Electronic Health Records
*Alzheimer Disease/diagnosis/psychology
*Mass Screening/methods
Los Angeles

@article {pmid41453000,
year = {2025},
author = {Olalusi, OV and Akinyemi, TO and Benedet, AL and Ogunde, GO and Yaria, JO and Cadmus, EO and Popoola, FO and Ogunronbi, M and Olujobi, D and Famuyiwa, O and Akinyemi, JO and Owolabi, MO and Romero-Ortuno, R and Udeh-Momoh, CT and Ogunniyi, A and Pericak-Vance, M and Kalaria, R and Lawlor, B and Zetterberg, H and Akinyemi, RO},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104142},
doi = {10.1002/alz70856_104142},
pmid = {41453000},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; Male ; Female ; Aged ; *Cognitive Dysfunction/blood/diagnosis ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; *Alzheimer Disease/blood/diagnosis ; *Hand Strength/physiology ; Longitudinal Studies ; Nigeria ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; Cohort Studies ; Aged, 80 and over ; Middle Aged ; Frailty/blood ; },
abstract = {BACKGROUND: Plasma biomarkers as well as non-invasive measures of frailty are increasingly employed to aid population-wide cognitive screening, phenotyping and preclinical diagnosis. Hand grip strength (HGS), a measure of physical and cardiometabolic health, is indicative of early cognitive decline but its relationship with plasma biomarkers of Alzheimer's Disease (AD) and neurodegeneration is not known. We investigated the association between HGS and plasma markers of AD and neurodegeneration in the Vascular heAlth, fraiLty, and cognItion in Ageing Nigerians (VALIANT) study.

METHOD: VALIANT is a longitudinal community-based cohort study. One thousand and thirty-six (1036) participants were recruited from Wards 2 and 3 of the Ibadan Northeast local government area of Oyo State, Nigeria through a multi-stage, stratified cluster random sampling method. Initial screening for cognitive dysfunction was performed using the IDEA, and MoCA scores. Patients were then diagnosed as having dementia and MCI via a consensus diagnosis of at least two neurologists. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)217 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive immunoassays. Biomarker data were log- and square-root transformed. Multiple linear regression analysis was employed to detect the relationship between HGS and plasma biomarkers, while adjusting for sociodemographic, lifestyle, cardiometabolic, social and cognitive function scores. β coefficient and corresponding 95% CI was reported. (p-value <0.05) RESULT: At baseline, a total of 35 participants (3.4%) and 112 (11%) had dementia and mild cognitive impairment (MCI) respectively. The mean (SD) age of participants was 77.0 (11.3) dementia, 72.6 (9.8) MCI and 63.8 (9.9) normal (p value<0.001). In the simple linear regression, significant bivariate relationship was observed between HGS and all the plasma biomarkers. In the multiple linear regression analysis, HGS showed an independent relationship with respective β (95% CI) of -0.0026 (-0.0051, -0.0001) for pTau217, 0.009 (0.002, 0.016) for Ab42, and -0.013 (-0.021, -0.004) for NfL.

CONCLUSION: Hand grip strength is independently associated with plasma markers of neurodegeneration in this cohort of community-dwelling older Nigerians individuals. Both measures could serve as potential screening tools for identifying individuals at risk for AD/ADRD, complementing other existing biomarkers.},
}

Humans
*Biomarkers/blood
Male
Female
Aged
*Cognitive Dysfunction/blood/diagnosis
Amyloid beta-Peptides/blood
tau Proteins/blood
*Alzheimer Disease/blood/diagnosis
*Hand Strength/physiology
Longitudinal Studies
Nigeria
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood
Cohort Studies
Aged, 80 and over
Middle Aged
Frailty/blood

@article {pmid41452999,
year = {2025},
author = {Sadeqi, H and Morshedizad, Z and Ahmadi, B and Burke, R and Armstrong, MJ and Babajani-Feremi, A},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106084},
doi = {10.1002/alz70858_106084},
pmid = {41452999},
issn = {1552-5279},
mesh = {Humans ; Male ; Aged ; Female ; *Parkinson Disease/physiopathology/psychology ; *Lewy Body Disease/physiopathology/psychology ; Magnetoencephalography ; *Brain/physiopathology ; },
abstract = {BACKGROUND: Lewy body dementia (LBD) is the second most common degenerative dementia after Alzheimer's disease, yet its underlying neural mechanisms, particularly those contributing to cognitive fluctuations, remain poorly understood.

METHOD: We analyzed resting-state MEG data from 28 participants in three cohorts: (a) LBD (n = 7, age = 70.1 ± 5.7 years, 5 males), (b) Parkinson's disease (PD) without cognitive impairment (n = 8, age = 71.1 ± 7.6 years, 3 males), and (c) normal cognitive (NC) (n = 13; age = 72.3 ± 6.5 years, 5 males). A six-state hidden Markov model (HMM) was applied to investigate brain state dynamics and cognitive fluctuations. Brain states were characterized by activation patterns across 52 regions of interest (ROIs). Four dynamic connectivity metrics were assessed: fractional occupancy (FO), mean lifetime (MLT), mean interval, and switching rate (SWR). Their correlations with the Clinician Assessment of Fluctuation (CAF) scale were also evaluated. Additionally, power spectral density (PSD) analysis was conducted to uncover neural signatures underlying cognitive variability in LBD.

RESULT: Power maps for each brain state revealed distinct activation patterns (Figure 1). The most pronounced group differences were observed in States 1 and 5 (Figure 2). State 1, primarily involving the medial prefrontal and lateral temporal cortices, showed significantly prolonged occupancy (higher FO and MLT) in LBD patients compared to NC and PD groups (p < 0.001). Conversely, State 5, which engaged the right temporo-parieto-occipital regions, was less active in LBD. PSD analysis indicated slowing in LBD, with activity shifting from the alpha band in NC and PD groups to the theta band in LBD (Figure 3). Moreover, dynamic connectivity measures were significantly correlated with CAF across all states. Notably, FO in State 1 exhibited a strong positive correlation with CAF (r = 0.72, p < 10[-24]), while FO in State 5 showed a strong negative correlation (r = -0.65, p < 10[-18]).

CONCLUSION: Our findings reveal distinct LBD-specific spectral slowing and dynamic connectivity patterns, characterized by prolonged engagement in temporal-prefrontal networks and reduced involvement in temporo-occipito-parietal regions. These alterations strongly correlate with cognitive fluctuations, suggesting potential biomarkers for LBD. Future research should explore targeting these abnormal state transitions to mitigate cognitive fluctuations.},
}

Humans
Male
Aged
Female
*Parkinson Disease/physiopathology/psychology
*Lewy Body Disease/physiopathology/psychology
Magnetoencephalography
*Brain/physiopathology

@article {pmid41452998,
year = {2025},
author = {Wolff, NL and Benzarti, CI and Henley, L and Stauffer, AL and Carter, BG and Rhodus, EK},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e105215},
doi = {10.1002/alz70858_105215},
pmid = {41452998},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Caregivers/psychology ; Aged ; *Dementia/psychology/nursing ; Aged, 80 and over ; *Communication Disorders/psychology/etiology ; Middle Aged ; *Alzheimer Disease/psychology ; },
abstract = {BACKGROUND: Declining communication is one of the hallmark symptoms of Alzheimer's disease and related dementias (ADRD). Not only is this symptom distressing for the person with ADRD, but care tasks may be more challenging as a result of communication deficits. While it is well known that hearing loss is strongly related to communication capacity, a lesser explored area related to communication is that of cortical-level sensory processing in ADRD. We hypothesized communication impairment would be positively correlated with caregiver burden and sensory processing abnormalities in older adults with ADRD.

METHOD: Using data collected from a non-pharmacological randomized controlled trial aimed at behavior modification in ADRD (participants with ADRD confirmed by Clinical Dementia Rating Scale [CDR] score of 1+ and their primary caregivers), this study conducted secondary data analysis using Pearson correlation to assess relationships among communication impairment as indicated on the CDR, caregiver burden (as measured by the Zarit Burden Inventory), and sensory processing abnormalities (as measured by the Adult Sensory Profile). Demographic data were assessed using summary statistical assessment.

RESULT: Data were analyzed from 19 participants with ADRD. Participants with ADRD consisted of 11 females, 8 males, x̄ age of 78.21 (SD=10.15), and x̄ Standard Global CDR of 1.63 (SD=0.84). All participants had functioning sensory acuity with or without aids (i.e., hearing aids). Care partners consisted of 16 females, 3 males, x̄ age of 62.32 (SD=11.56), and spouses were the most frequent care partners. Analyses indicated a significant strong positive correlation between communication impairment and caregiver burden (r = 0.59, p = 0.007). Additionally, communication impairment was significantly positively correlated with sensory processing abnormalities within the domains of sensory sensitivity (r = 0.64, p = 0.004) and sensory avoiding (r = 0.49, p = 0.037).

CONCLUSION: Both receptive (hearing) and expressive (talking) communication is vital to encourage cooperative completion of care tasks. Communication impairment in ADRD is not only linked to increased caregiver burden, but also is associated with cortical-level sensory processing abnormalities beyond standard hearing loss. Combined with hearing loss, communication is made even more difficult. Additional exploration is warranted to determine causal mechanisms between sensory processing abnormalities and communication impairment in ADRD.},
}

Humans
Female
Male
*Caregivers/psychology
Aged
*Dementia/psychology/nursing
Aged, 80 and over
*Communication Disorders/psychology/etiology
Middle Aged
*Alzheimer Disease/psychology

@article {pmid41452996,
year = {2025},
author = {Winford, ED and Huber, BD and Mazen, J and Brickman, A and Manly, JJ},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103420},
doi = {10.1002/alz70856_103420},
pmid = {41452996},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Middle Aged ; Biomarkers/blood ; *Alzheimer Disease/genetics/blood ; *Cytokines/blood ; Aged ; *Inflammation/blood ; Parents ; White People ; White ; },
abstract = {BACKGROUND: Peripheral inflammation is a known contributor to Alzheimer's disease (AD) risk and progression. As aging is associated with increasing inflammation that may precede AD onset, individuals with a parental history of AD, a risk factor that increases lifetime AD risk, may have inflammatory profiles that reflect their risk. This study examines whether having a parent with AD is associated with increased peripheral inflammation in middle-aged adults. We hypothesize that individuals with parental history of AD will have higher levels of pro-inflammatory cytokines compared with those without a parental history of AD across racial and ethnic groups.

METHOD: Participants comprised 1,043 non-Hispanic White, non-Hispanic Black, and Hispanic men and women from the Offspring Study who are the adult children of participants in the Washington Heights Inwood Columbia Aging Project. Parental AD status was determined by a diagnostic consensus conference. Plasma chemokine and cytokine concentrations were assayed with Luminex technology. were used for the associations between parental AD status and inflammatory cytokines, adjusting for age and sex, and interaction models were used to determine if associations differed by age, sex at birth, race and ethnicity, or APOE genotype.

RESULT: Participants with a parental history of AD (n = 660, mean age=54, 65% women) had higher levels of Eotaxin (log-diff: 0.09, 95% CI: 0.01,.0.15) and lower levels of G-CSF (-0.2, 95% CI: -0.35,-0.04), VEGF-A (-0.16, 95% CI: -0.3,-0.01), and IL-27 (-0.07, 95% CI: -0.15,0.0) compared with those without a parental history of AD (n = 383, mean age=60, 71% women). IL-18 levels were significantly higher in Black individuals with a parental history of AD compared to Black individuals without, while White individuals with a parental history of AD had higher levels of EGF compared to White individuals without. Women with a parent history of AD had higher levels of IFna2, IL-12p70, sCD40L, and IL-18 compared to women without parental AD history.

CONCLUSION: Parental history of AD is associated with elevated markers of peripheral inflammation. These associations vary across sex and race and ethnicity.},
}

Humans
Female
Male
Middle Aged
Biomarkers/blood
*Alzheimer Disease/genetics/blood
*Cytokines/blood
Aged
*Inflammation/blood
Parents
White People
White

@article {pmid41452994,
year = {2025},
author = {Annettesdotter, A and Spotorno, N and Wuestefeld, A and Mattsson-Carlgren, N and Strandberg, O and Ossenkoppele, R and Stomrud, E and Palmqvist, S and Wolk, DA and Hansson, O and Wisse, LEM},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103071},
doi = {10.1002/alz70856_103071},
pmid = {41452994},
issn = {1552-5279},
mesh = {Humans ; Male ; *Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging/pathology/diagnosis ; *Amyloid beta-Peptides/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid ; Female ; Aged ; Disease Progression ; Positron-Emission Tomography ; tau Proteins/cerebrospinal fluid ; *Brain/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Aged, 80 and over ; Neuropsychological Tests ; Middle Aged ; Dementia ; Mental Status and Dementia Tests ; },
abstract = {BACKGROUND: A considerable portion of patients with amnestic mild cognitive impairment (aMCI) have negative amyloid-β (Aβ) biomarkers and are therefore unlikely to have Alzheimer's disease (AD). Potential causes of cognitive decline in this heterogeneous group include limbic-predominant age-related TDP-43 encephalopathy (LATE), cardio/cerebrovascular diseases, primary age-related tauopathy (PART), and subthreshold Aβ. The prognosis of Aβ-negative (Aβ-) aMCI patients, putatively more benign, is unclear. We aim to investigate which predictors - including demographics, baseline cognition, fluid and imaging biomarkers - can best predict cognitive decline and progression to dementia in Aβ- aMCI.

METHOD: We included 140 Aβ- aMCI patients (Aβ status based on cerebrospinal fluid (CSF) and positron emission tomography, when available; 'amnestic' based on norm scores for AD Assessment Scale delayed word recall) from BioFINDER-1/2 with longitudinal Mini-Mental State Examination (MMSE), and subsets with longitudinal data on Clinical Dementia Rating Sum of Boxes (CDR-SB; n = 67) and progression to dementia (n = 134, 43% progressors; Table 1). Predictors included global and regional atrophy measures, specific for LATE and PART, CSF Aβ42/40 and p-tau181, hypertension, white matter hyperintensities and global cognition. Individual MMSE and CDR-SB slopes were estimated with linear mixed-effects models. Associations of predictors with MMSE/CDR-SB slopes and progression to dementia were tested. Significant predictors and demographic variables were included in the model selection process using R package MuMIn, which tests linear combinations of variables and ranks models by the Akaike information criterion (AIC).

RESULTS: Figure 1 shows individual associations for the identification of significant predictors for the model selection process. For MMSE (AIC: 350.57; Figure 2a), the selected most parsimonious model included baseline MMSE and whole-brain cortical thickness. For CDR-SB (AIC: 176.73; Figure 2b), baseline CDR-SB, amygdala volume, and middle frontal gyrus cortical thickness were included. For progression to dementia (AIC: 97.65; Figure 2c), the selected model included MMSE, lateral ventricles volume, entorhinal and whole-brain cortical thickness, sex and CSF Aβ42/40.

CONCLUSIONS: Baseline cognition, global and regional atrophy measures are valuable predictors of cognitive decline in Aβ- aMCI, with regional brain measures hinting at specific pathologies. These prediction models are relevant for the new LATE clinical criteria. We aim to validate our findings in ADNI.},
}

Humans
Male
*Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging/pathology/diagnosis
*Amyloid beta-Peptides/cerebrospinal fluid
*Biomarkers/cerebrospinal fluid
Female
Aged
Disease Progression
Positron-Emission Tomography
tau Proteins/cerebrospinal fluid
*Brain/diagnostic imaging/pathology
Magnetic Resonance Imaging
Aged, 80 and over
Neuropsychological Tests
Middle Aged
Dementia
Mental Status and Dementia Tests

@article {pmid41452990,
year = {2025},
author = {Sherimon, V and Varghese, A and P C, S},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103324},
doi = {10.1002/alz70856_103324},
pmid = {41452990},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Biomarkers ; Neuroimaging ; },
abstract = {BACKGROUND: Research on Alzheimer's disease (AD) requires comprehensive data resources to better understand the complex relationships among genetic, environmental, and clinical variables influencing disease onset and progression. This review systematically analyses significant AD datasets, emphasizing their technical attributes, analytical challenges, and methodological factors to enhance research usability in this domain.

METHOD: We performed a comprehensive review of published literature and data repositories relevant to AD research. Datasets such as ADNI, NACC, OASIS, Clinical Trial Data (A4, LEARN), and open-access repositories (AD, Knowledge Portal) were examined. The evaluated key characteristics comprised sample size, data modalities (neuroimaging, genomics, proteomics, clinical, longitudinal coverage, data access policies, and identified constraints).

RESULT: Comprehensive initiatives such as ADNI, and NACC contribute essential multimodal data, enabling research on AD biomarkers, progression, and treatment efficacy. Nonetheless, intrinsic issues include: Data Heterogeneity: Inconsistencies in diagnostic criteria, evaluation methodologies, and imaging modalities among studies impede data synchronization and comparability (e.g., MCI diagnosis inconsistencies between NACC and ADNI) Missing Data: Incomplete datasets require precise management of missing values to prevent skewed analysis. Sophisticated techniques for imputation and sensitivity analysis are essential. Class Imbalance: Unequal representation of diagnostic categories (e.g., normal, MCI, AD) might affect the efficacy of machine learning models, necessitating approaches such as data augmentation (SMOTE) or cost-sensitive learning. High Dimensionality: The integration of multiomics data requires feature selection techniques (such as genetic algorithms and modified particle swam optimization) to determine the most significant aspects and mitigate computational complexity.

CONCLUSION: Despite the above limitations, current AD datasets have contributed to significant advancements. Future research should focus on: Standardization: Supporting uniform data gathering and processing techniques across research initiatives. Data Integration: Formulating effective strategies for integrating multi-omics, neuroimaging, and clinical data to explain the complex relationships of variables driving AD. Advanced Analytics: Implementing complex machine learning methodologies to address class imbalance, missing data, and high dimensionality while ensuring model interoperability and generalizability. Open Science: Promoting open data sharing to enhance collaborative research and optimize data value. This review underlines the necessity for continuous initiatives to enhance data quality, address methodological challenges, and support for open science principles to expedite AD research.},
}

Humans
*Alzheimer Disease/diagnosis
*Biomarkers
Neuroimaging

@article {pmid41452989,
year = {2025},
author = {Ghosh, S and Singh, KK and Pandey, AK and Jha, S and Sinha, JK},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104338},
doi = {10.1002/alz70856_104338},
pmid = {41452989},
issn = {1552-5279},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Biomarkers/metabolism ; *Mitochondria/metabolism/pathology ; *Aging/metabolism ; Animals ; },
abstract = {BACKGROUND: Mitochondrial dysfunction is an integral feature of both aging and neurodegenerative diseases, where it significantly contributes to disease progression. It is, therefore, of the utmost importance to understand the underlying mechanisms so that effective therapeutic approaches can be developed. This article delves into specific pathways where mitochondrial dysfunction occurs in aging and neurodegenerative conditions in the hope of discovering potential targets for intervention.

METHODS: A comprehensive literature review was done to synthesize current knowledge on mitochondrial dysfunction in ageing and neurodegeneration. It focused on the key cellular and molecular pathways that include changes in mitochondrial structure and function, disruptions in energy metabolism, and their impact on cellular homeostasis.

RESULTS: In short, the overall data point to complex interactions between the processes of aging, neurodegenerative disease and mitochondrial dysfunction. During aging, mitochondria become functionally less effective, characterized by decreased ATP levels, impaired oxidative phosphorylation and increased reactive oxygen species production. Different neurodegenerative diseases- Alzheimer's disease, Parkinson's disease, Huntington's disease-had specific abnormalities in mitochondria, including deficient mitophagy, altered dynamics of mitochondria, and mutation in mitochondrial DNA. These cause neuronal cell death and accelerate progression of the diseases.

CONCLUSION: This study elucidates the diverse mechanisms that connect mitochondrial dysfunction with both ageing and neurodegenerative diseases. Various pathways identified in this review are considered critical areas for therapeutic intervention aimed at preserving mitochondrial integrity and subsequently reducing detrimental impact of ageing and neurodegeneration on cellular function. These mechanisms offer more complex avenues for research into these critical pathways that should lead to novel treatments for age-related and neurodegenerative conditions.},
}

Humans
*Neurodegenerative Diseases/metabolism
*Biomarkers/metabolism
*Mitochondria/metabolism/pathology
*Aging/metabolism
Animals

@article {pmid41452980,
year = {2025},
author = {Chakraborty, S and Jamuna Tripathi, S and Vázquez-Rosa, E and Chaubey, K and Fujioka, H and Miller, E and Tyagi, R and Vignane, T and Sharma, SM and Thomas, B and Weil, ZM and Nelson, RJ and Filipovic, MR and Orsburn, BC and Snyder, SH and Pieper, AA and Paul, BD},
title = {Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {52},
pages = {e2528478122},
doi = {10.1073/pnas.2528478122},
pmid = {41452980},
issn = {1091-6490},
support = {1R01AG071512-01//HHS | NIH | National Institute on Aging (NIA)/ ; 1R01AG071512-01//HHS | NIH | National Institute on Aging (NIA)/ ; 1R21AG073684-01//HHS | NIH | National Institute on Aging (NIA)/ ; I01BX005976//U.S. Department of Veterans Affairs (VA)/ ; 19PABH134580006//American Heart Association (AHA)/ ; RO1AGs066707//HHS | NIH | National Institute on Aging (NIA)/ ; 1 U01 AG073323//HHS | NIH | National Institute on Aging (NIA)/ ; AG077396//HHS | NIH | National Institute on Aging (NIA)/ ; NS101967//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS133688//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; HT94252310443//DOD | Department of Defense Education Activity (DoDEA)/ ; },
mesh = {Animals ; *Cystathionine gamma-Lyase/metabolism/genetics ; *Neurogenesis/physiology ; *Signal Transduction/physiology ; Mice ; *Cognition/physiology ; *Nerve Growth Factors/metabolism ; Blood-Brain Barrier/metabolism ; Mice, Knockout ; Oxidative Stress ; },
abstract = {Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer's disease and Huntington's disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood-brain barrier integrity, impair neurogenesis and neurotrophin signaling, and elicit cognitive deficits. Global proteomic analysis further revealed molecular alterations that contribute to impaired neurogenesis. Our findings establish CSE as an essential guardian of homeostatic brain health and identify it as a potential therapeutic target for neurodegenerative disorders.},
}

Animals
*Cystathionine gamma-Lyase/metabolism/genetics
*Neurogenesis/physiology
*Signal Transduction/physiology
Mice
*Cognition/physiology
*Nerve Growth Factors/metabolism
Blood-Brain Barrier/metabolism
Mice, Knockout
Oxidative Stress

@article {pmid41452978,
year = {2025},
author = {Weng, JEM and Noristani, HN and Schuldt, CE and Lacor, PN},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103597},
doi = {10.1002/alz70856_103597},
pmid = {41452978},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/pathology/genetics/metabolism ; *Biomarkers/metabolism ; *Cerebral Amyloid Angiopathy/pathology/genetics/metabolism ; *Brain/pathology/metabolism ; Male ; Female ; Plaque, Amyloid/pathology/metabolism ; Aged ; Transcriptome ; },
abstract = {BACKGROUND: Cerebral amyloid angiopathy (CAA) is a major co-pathology exhibited by over 80% of Alzheimer's disease (AD) patients. This neuropathological hallmark is defined by an accumulation of amyloid deposits in cerebral cortical and leptomeningeal vessels. Although pathogenesis is poorly understood, CAA leads to perivascular leakage, microaneurysms and an increased risk of cerebral hemorrhages, along with an elevated neuroinflammatory response. To identify CAA-specific inflammatory pathways, we conducted -omics studies using the GeoMx® digital spatial profiler (DSP) in pathology-enriched microenvironments such as amyloid deposition (plaques, parenchymal and leptomeningeal CAA) in postmortem human brain regions from AD patients with and without CAA.

METHOD: Using the comprehensive whole transcriptome atlas (WTA) targeting 18,000 transcripts, we analyzed gene expression of pathologically relevant pathways in precise microenvironments across two preservation modalities (formalin-fixed paraffin-embedded vs fresh frozen). Additionally, we conducted GeoMx spatial profiling with neuro- and immune-specific protein panels, on regions of interest (ROI) designed with the Visiopharm image analysis platform, affording greater cell-type specific resolution.

RESULT: Across both preservations, 7090 genes were detected in at least 10% of ROIs; however, over +2000 genes were uniquely detected in Frozen, while only 740 unique genes in FFPE tissue. Across Frozen tissue, the gene expression profile of AD+CAA estimated fewer neuronal and an increase in pericyte and astrocyte markers, compared to AD and control. Further, enrichment analysis demonstrated that, within amyloid plaque enriched microenvironments, AD+CAA expression profile was associated with vasculature development, T cell activation and inflammatory response, while AD was associated with synaptic and mitochondrial function. GeoMx proteomic assessment of 120+ proteins confirmed the upregulation of activated microglia and reactive astrocytes within amyloid enriched microenvironments with additional differentiation in parenchymal CAA, as evident by an enrichment of glial fibrillary acidic protein, vimentin and complement C4B. Additionally, perivascular immune cells surrounding leptomeningeal vessels with CAA exhibited the characteristics of cytotoxic T cells.

CONCLUSION: Based on our findings, reactive astrocytic and macrophagic markers are potential valuable biomarkers of CAA in AD. Therefore, this study provides valuable insights into the inflammatory pathways specific to CAA, elucidating our understanding of this AD co-pathology.},
}

Humans
*Alzheimer Disease/pathology/genetics/metabolism
*Biomarkers/metabolism
*Cerebral Amyloid Angiopathy/pathology/genetics/metabolism
*Brain/pathology/metabolism
Male
Female
Plaque, Amyloid/pathology/metabolism
Aged
Transcriptome

@article {pmid41452971,
year = {2025},
author = {Buckova, BR},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103112},
doi = {10.1002/alz70856_103112},
pmid = {41452971},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers ; *Neuroimaging/methods ; Cross-Sectional Studies ; *Alzheimer Disease/diagnostic imaging ; *Brain/diagnostic imaging ; Longitudinal Studies ; Male ; },
abstract = {The growth of large-scale neuroimaging collaborations has opened new opportunities for analyzing data at an unprecedented scale, driving the development of methods that exploit data variation to deepen our understanding of both healthy population variation and disease-specific patterns. Among these methods, normative modeling stands out as a powerful framework that relates individual neuroimaging data to population-derived standards. This approach models an individual's neuroimaging phenotypes in relation to demographic and clinical variables within a large, healthy population, enabling subject-level inferences about their position relative to the population. While normative models excel in establishing robust population norms and identifying disease-specific patterns, their potential for analyzing temporal dynamics has yet to be fully realized. The cross-sectional nature of most datasets limits the ability to model subject-level trajectories over time. Furthermore, existing methods for analyzing longitudinal data often fail to integrate insights from large-scale cross-sectional datasets, hindering the detection of early markers of neurodegeneration or subtle deviations from typical aging trajectories. To address this limitation, we introduce an innovative normative modeling approach that leverages the heterogeneity in large cross-sectional datasets and also incorporates longitudinal dynamics for subject-specific inferences. This method builds upon pre-trained normative models derived from over 58,000 individuals, offering scalability, flexibility, and applicability across studies with varying sample sizes. By comparing an individual's trajectory with the expected dynamics derived from population norms, our approach enables the detection of atypical changes that might otherwise go unnoticed. The result of this method is an individualized score, which quantifies whether a significant change has occurred in each individual over time, allowing for more precise detection of deviations from typical trajectories. This technique holds particular promise for Alzheimer's disease research, where early detection and tracking of disease progression are critical. By integrating cross-sectional and longitudinal data, our framework improves the ability to detect subtle changes over time, contributing to a more nuanced understanding of neurodegeneration. Furthermore, this approach is versatile and can be extended to other neurological and psychiatric conditions, providing a powerful tool for analyzing longitudinal neuroimaging data across a wide range of studies.},
}

Humans
*Biomarkers
*Neuroimaging/methods
Cross-Sectional Studies
*Alzheimer Disease/diagnostic imaging
*Brain/diagnostic imaging
Longitudinal Studies
Male

@article {pmid41452955,
year = {2025},
author = {Karagianni, S and Rial, AM and van Essen, M and Mainta, I and Camacho, V and Rodríguez-Fonseca, O and Perissinotti, A and Grothe, MJ and Garibotto, V and Schöll, M},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104257},
doi = {10.1002/alz70856_104257},
pmid = {41452955},
issn = {1552-5279},
mesh = {Humans ; *tau Proteins/blood ; *Biomarkers/blood ; *Alzheimer Disease/pathology/blood/diagnostic imaging ; Male ; Female ; Amyloid beta-Peptides/blood ; Positron-Emission Tomography ; Aged ; Aged, 80 and over ; Autopsy ; Brain/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: In vivo detection of intermediate and high Alzheimer's disease neuropathologic changes (ADNC) is key for disease staging and clinical trial enrolment. While a visually positive tau-PET scan with the FDA/EMA-approved tracer [[18]F]flortaucipir can be considered a reliable proxy of high ADNC (Fleisher et al., 2024), plasma biomarkers such as tau phosphorylated at threonine 217 (p-tau217) are emerging as minimally-invasive alternatives. This study evaluates the performance of commercially-available plasma p-tau217 in identifying intermediate and high ADNC defined by neuropathologic assessments at autopsy as well as by visual reads of FDA/EMA-approved in vivo tau-PET scans.

METHOD: Postmortem neuropathologic evaluations and antemortem plasma p-tau217 and Aβ42/Aβ40 measurements (Lumipulse G1200 assay) from 110 ADNI participants were included. In addition, plasma biomarkers were assessed in 625 additional ADNI participants and for 403 A4 participants plasma p-tau217 (MesoScale ECL assay) was included. All participants underwent [[18]F]flortaucipir PET. Three trained readers rated the [[18]F]flortaucipir scans as visually positive/negative using the FDA/EMA-approved interpretation method. Receiver operating characteristic (ROC) curve analysis assessed the biomarkers' discriminative accuracy across ADNC levels.

RESULT: Plasma p-tau217 biomarkers demonstrated high accuracy (AUC>0.93) for discriminating between "no/low/intermediate" and "high" ADNC at autopsy (Figure 1A). When applying externally derived two-tier cut-points for plasma p-tau217 (negative/intermediate/positive), it identified "no" or "high" ADNC accurately (80-93%) (Figure 1B-C). However, for detecting low/intermediate ADNC, high variability was observed, with only 40-65% of the low ADNC cases classified as negative and 35-57% of the intermediate ADNC cases classified as positive (Figure 1C). Findings in the in vivo cohort examined with tau-PET supported these results. Plasma biomarkers reliably identified high ADNC as reflected by the PET-based A+T+ profile, but the majority of the A+T- individuals were classified as intermediate or negative (Figure 2C-E and Figure 3C-E). Plasma biomarkers yielded higher accuracy in cognitively impaired (Figure 3A-B) than in unimpaired individuals (Figure 2A-B).

CONCLUSION: Plasma p-tau217 markers effectively classify ADNC extremes but are less reliable for accurately assessing low/intermediate ADNC levels, reflecting their limited utility for biological disease staging. This weaker performance in preclinical cases, including failure to reliably identify A+T- cases as positive, challenges their potential role in early AD detection. Complementary imaging may be needed to improve reliability in early stages.},
}

Humans
*tau Proteins/blood
*Biomarkers/blood
*Alzheimer Disease/pathology/blood/diagnostic imaging
Male
Female
Amyloid beta-Peptides/blood
Positron-Emission Tomography
Aged
Aged, 80 and over
Autopsy
Brain/pathology/diagnostic imaging

@article {pmid41452943,
year = {2025},
author = {Stites, SD and Adams, M and Kuz, C and Halberstadter, K and Humphreys, V and McMillan, CT and Mechanic-Hamilton, D},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e104383},
doi = {10.1002/alz70858_104383},
pmid = {41452943},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; DNA Methylation ; *Dementia/genetics/psychology ; *Caregivers/psychology ; *Aging/genetics/psychology ; *Parent-Child Relations ; Aged, 80 and over ; *Parents/psychology ; Surveys and Questionnaires ; Epigenesis, Genetic ; },
abstract = {BACKGROUND: A parent's well-being is instrumental for the child's safety, health and enrichment and these factors are all known to contribute to poorer late-life health outcomes. Epigenetic age, measured using DNA methylation, represents a biological feature of aging that reflects the extent to which an individual is accelerated or decelerated relative to their chronological age. Here we evaluate how parental relationship type and well-being associate with later life epigenetic age.

METHOD: Cognitively unimpaired older (>65 years) adults (N = 152) completed the Penn Alzheimer's Disease Research Center's Life Experience Survey. Questions inquired about relationship type (i.e., mother, father, aunt etc.) and overall well-being of up to three childhood caregivers. Ratings were from 0-100 with higher being better. Participants also completed measures of socioeconomic status and sociodemographic data. DNA methylation was measured using genomic blood and the Illumina EPIC array to compute Horvath and Levine epigenetic clocks. Linear regression models examined effects of parental relationship type and parental well-being ratings on age acceleration in bivariate models, which permitted examination of single parents and types of dyads (i.e., mother-father, mother-grandmother) and trivariate models, which allowed each parent relationship type to covary independently. Multivariable models controlled for potential confounding from socioeconomic status, adverse childhood events, and key demographic factors.

RESULTS: Father relationship type showed a statistical trend toward decelerated aging (Horvath, β=3.5, 95%CI -0.02 to 7.0). In bivariate models, better parental well-being was associated with decelerated aging (Levin, β=0.14, 95%CI 0.02, 0.24). Secondary parent well-being showed no effect. In trivariate models, better primary parent well-being was associated with decelerated aging (Levin, β=0.14, 95%CI 0.02, 0.24; Horvath, β=0.09, 95%CI 0.03, 0.10). Secondary parent well-being higher than the primary parent's was associated with accelerated aging (Levin, β=-0.08, 95%CI -0.2 to 0.02, p = 0.05; Horvath, β=-0.09, 95%CI -0.1, -0.03). These associations remained in multivariable models.

CONCLUSION: Our findings provide evidence for protective and negative biological aging outcomes associated with primary compared to secondary parental well-being. Thus, it is important to consider social context on aging outcomes. The findings underscore the import of caregivers in the health of older adults. This research line may inform population-level health interventions.},
}

Humans
Male
Female
Aged
DNA Methylation
*Dementia/genetics/psychology
*Caregivers/psychology
*Aging/genetics/psychology
*Parent-Child Relations
Aged, 80 and over
*Parents/psychology
Surveys and Questionnaires
Epigenesis, Genetic

@article {pmid41452901,
year = {2025},
author = {Yang, KL and DiFilippo, AH and Hammad, Y and Ma, Y and Wilson, RE and Pasquesi, ME and Jonaitis, EM and Barnhart, TE and Engle, JW and Betthauser, TJ and Ashton, N and Johnson, SC and Christian, BT and Zetterberg, H and Bendlin, BB},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103318},
doi = {10.1002/alz70856_103318},
pmid = {41452901},
issn = {1552-5279},
mesh = {Humans ; Male ; *tau Proteins/blood ; Female ; Biomarkers/blood ; Positron-Emission Tomography ; *Alzheimer Disease/diagnostic imaging/blood/pathology ; Aged ; *Brain/diagnostic imaging/metabolism/pathology ; Aged, 80 and over ; Phosphorylation ; Cognitive Dysfunction/diagnostic imaging ; },
abstract = {BACKGROUND: Phosphorylated tau and amyloid are known to cluster in synaptosomes in Alzheimer's disease (AD). Their presence in synapses may contribute to synaptic loss, although this relationship is not well understood. Plasma phosphorylated tau at position 217 (pTau217) represents tau secreted from neurons, is an accurate biomarker of AD pathology, and could potentially shed light on the processes preceding synaptic loss and cognitive impairment. Here we examine this relationship in medial-temporal brain regions susceptible to AD pathology accumulation.

METHODS: This analysis included 50 participants enrolled in the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Prevention with plasma data and [C-11]UCB-J PET scans (Table). Plasma pTau217 was determined using the ALZpath pTau217 Simoa assay on Quanterix HD-X platform. We used Logan Graphical Analysis with a whole cerebellar reference region to quantify synaptic density from [C-11]UCB-J scans, and identified ROIs (entorhinal cortex, hippocampus, fusiform gyrus, parahippocamphal gyrus, amygdala, and temporal pole) using FreeSurfer T1w-MRI parcellation. Amyloid positivity was determined using [C-11]PiB PET scans with a global DVR index [3]1.19. We utilized multiple regression analysis to examine the extent to which plasma pTau217 and whether having cognitive impairment associated with synaptic density in ROIs controlling for age and amyloid status. All models were fitted in R and considered significant at unadjusted p <.05. Effect sizes were assessed using Cohen's f[2].

RESULTS: Higher levels of plasma pTau217 (b=.13, p = 0.02) associated with higher synaptic density in the entorhinal cortex and cognitive impairment (b=-.09, p = 0.02) associated with lower synaptic density in this same region with small-to-moderate effect sizes (f[2]=.13 and f[2]=.12, respectively; see Figure). Cognitive impairment was associated with lower UCB-J DVR in the hippocampus (b=-.07, p <.05) with a moderate-to-large effect size of f[2]=.31.

CONCLUSIONS: The unexpected directional relationship between pTau217 and synaptic density in the medial temporal lobe could be due to an early compensatory response to pathology accumulation since most individuals in this sample were cognitively unimpaired. Longitudinal studies are forthcoming to determine the trajectory of plasma pTau217 and synaptic density.},
}

Humans
Male
*tau Proteins/blood
Female
Biomarkers/blood
Positron-Emission Tomography
*Alzheimer Disease/diagnostic imaging/blood/pathology
Aged
*Brain/diagnostic imaging/metabolism/pathology
Aged, 80 and over
Phosphorylation
Cognitive Dysfunction/diagnostic imaging

@article {pmid41452896,
year = {2025},
author = {Yiallourou, S and Kautz, TF and Parker-Garza, J and Cribb, L and Kohlfeld, P and Sullivan, AC and LaRoche, A and Tanner, JA and Fongang, B and Satizabal, CL and Wiedner, C and Himali, JJ and Cruchaga, C and Gonzales, MM and Seshadri, S and Pase, MP},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104637},
doi = {10.1002/alz70856_104637},
pmid = {41452896},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; Male ; Female ; Aged ; *Alzheimer Disease/blood/diagnosis ; *Frontotemporal Dementia/blood/diagnosis ; Diagnosis, Differential ; Machine Learning ; Amyloid beta-Peptides/blood ; *Lewy Body Disease/blood/diagnosis ; *Parkinson Disease/blood/diagnosis ; Middle Aged ; tau Proteins/blood ; },
abstract = {BACKGROUND: Plasma biomarkers demonstrate strong performance in detecting Alzheimer's disease (AD). However, their role in the differential diagnosis of dementia subtypes remains underexplored, particularly in the early clinical stages of AD, frontotemporal dementia (FTD), and Lewy body/Parkinson's disease (LBD/PD) dementia. This study aimed to evaluate the performance of plasma biomarkers in differentiating these dementia subtypes using a machine-learning approach.

METHODS: Patients with a clinical diagnosis of early AD, FTD, and LBD/PD dementia were recruited from the Knight ADRC at Washington University and the Biggs Institute for Alzheimer's and Neurodegenerative Diseases. Plasma samples were analyzed for markers of neuropathology, neuronal injury, and neuroinflammation, including Aβ40, Aβ42, pTau181, pTau217, TDP-43, NfL, GFAP, and YKL40. All biomarkers were measured centrally (Biggs Institute) on the Simoa platform, except YKL40 (MSD). Dementia subtype classification models (e.g., AD vs. others) were developed using the SuperLearner algorithm, which combines multiple machine learning models into an optimally weighted prediction. Models included age, sex, and all plasma biomarkers. Performance was assessed using cross-validated area under the receiver operating characteristic curve (AUC). The contribution of each biomarker to the AUC was calculated by comparing the full model to a restricted model excluding that biomarker.

RESULTS: Biomarker data was obtained on 162 patients with AD, 70 with FTD, and 109 with LBD/PD (Table 1). Models combining all biomarkers showed excellent discrimination of AD dementia (AUC=0.84) and FTD (AUC=0.85) from other dementias, and moderate discrimination for LBD/PD dementia (AUC=0.72; Figure 1). Among individual biomarker contributions (Table 2), pTau217 was the strongest predictor for AD differentiation. The low individual contributions for FTD suggest that FTD differentiation was driven by a combination of biomarkers, with NfL showing the highest individual contribution. For LBD/PD, Aβ40 and pTau217 contributed the most, though model performance was moderate.

CONCLUSION: pTau217 emerged as the key biomarker for AD differentiation. The smaller independent contributions of individual biomarkers to FTD classification suggest that predictive information is shared across multiple markers, with NfL having the highest contribution. Plasma biomarkers show strong potential for aiding early, non-invasive differential diagnosis of AD and FTD. Further optimization is needed for LBD/PD classification.},
}

Humans
*Biomarkers/blood
Male
Female
Aged
*Alzheimer Disease/blood/diagnosis
*Frontotemporal Dementia/blood/diagnosis
Diagnosis, Differential
Machine Learning
Amyloid beta-Peptides/blood
*Lewy Body Disease/blood/diagnosis
*Parkinson Disease/blood/diagnosis
Middle Aged
tau Proteins/blood

@article {pmid41452870,
year = {2025},
author = {Kim, GH and Kang, D and Kang, SH and Kim, JS and Youn, YC and Lim, JS and Moon, SY and Moon, WJ and Park, YH and Shim, Y and Yang, DW and Cho, H and Choi, H and Pyun, JM and Park, KH and Choi, SH},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106260},
doi = {10.1002/alz70858_106260},
pmid = {41452870},
issn = {1552-5279},
mesh = {Humans ; Republic of Korea ; *Registries ; *Dementia/psychology/therapy ; *Alzheimer Disease/therapy/psychology ; *Biomedical Research ; },
abstract = {Alzheimer's disease (AD) is undergoing a transformation with disease-modifying therapies (DMTs) and advanced biomarkers, shifting from symptomatic management to targeted interventions. However, high costs, potential side effects, and limited awareness hinder real-world integration, particularly in underrepresented East Asian populations like Koreans. Preliminary data suggest East Asians may experience lower rates of Amyloid-Related Imaging Abnormalities (ARIA), emphasizing the need for region-specific treatment guidelines. To address this, the Korean Dementia Association (KDA) launched JOY-ALZ (Korean JOint RegistrY for ALZheimer's Treatment and Diagnostics) in 2024 to establish a real-world data (RWD) platform for AD therapies in Korea. Overall objectives of JOY-ALZ are: • Develop a collaborative network across multiple sites for systemic patient data collection. • Record comprehensive patient data on cognitive, functional, and safety outcomes. • Enhance data acquisition by integrating neuroimaging, genetic, and biomarker data • Assess health outcomes using existing databases for long-term evaluation. • Maximize data sharing with researchers and stakeholders. To achieve this, JOY-ALZ employs the CURE Framework, which encompasses four specific aims: • Creating the RWD platform infrastructure • Uncovering outcomes: collecting data to evaluate long term safety and clinical outcomes • Reinforcing collaborations: co-enrollment with affiliated studies • Enabling global sharing: data sharing and linking Following Korean regulatory approval of lecanemab in May 2024, JOY-ALZ published Appropriate Use Recommendations (AUR) in October 2024 and hosted educational symposia. IRB submissions were initiated in December 2024 across 41 hospitals, with approval expected by June 2025 to enable comprehensive real-world data (RWD) collection, including clinical data, neuroimaging, and biosamples. In the long term, JOY-ALZ will complement global platforms like ALZ-NET, informing Korean-specific treatment guidelines, promoting equitable access to AD therapies, and fostering international collaboration by contributing high-quality RWD to the global research community. JOYALZ will play a key role in advancing AD research by leveraging RWD collected through Korea's dementia clinic network.},
}

Humans
Republic of Korea
*Registries
*Dementia/psychology/therapy
*Alzheimer Disease/therapy/psychology
*Biomedical Research

@article {pmid41452866,
year = {2025},
author = {Dannert, A},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e100354},
doi = {10.1002/alz70855_100354},
pmid = {41452866},
issn = {1552-5279},
mesh = {Humans ; *tau Proteins/genetics/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Neurons/metabolism/pathology ; *Tauopathies/pathology/genetics/metabolism ; Protein Isoforms/genetics/metabolism ; CRISPR-Cas Systems ; },
abstract = {BACKGROUND: Tauopathies, such as Alzheimer's disease and Frontotemporal Dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of Tau. Molecular mechanisms underlying Tauopathies are still poorly understood, in part due to a lack of human models endogenously developing major disease hallmarks. Adult Tau isoform expression contributes to Tau pathogenesis but is challenging to replicate in human stem-cell-derived systems, which impedes formation of late-stage disease phenotypes and hence research on underlying mechanisms and drug development.

METHOD: We developed a novel iPSC-based cortical neuron model in which we altered Tau isoform expression to match adult human neurons. For this, we used a multi-step CRISPR/Cas9 genome editing strategy that changes endogenous Tau isoform expression from the genomic MAPT locus.

RESULT: We found that induction of adult human brain-like 4R Tau isoform expression enables endogenous formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we found proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate a human Tau PET tracer.

CONCLUSION: Collectively, our model enables novel investigations on endogenous mechanisms of human Tauopathy formation, suggesting a central role of 4R Tau isoform expression for pathogenesis in human neurons. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs.},
}

Humans
*tau Proteins/genetics/metabolism
*Induced Pluripotent Stem Cells/metabolism
*Neurons/metabolism/pathology
*Tauopathies/pathology/genetics/metabolism
Protein Isoforms/genetics/metabolism
CRISPR-Cas Systems

@article {pmid41452865,
year = {2025},
author = {Dammer, EB and Afshar, S and Bian, S and Bennett, DAA and Mohs, R and Beauregard, DW and Dwyer, J and Seyfried, NT and Roberts, BR and Manzanares, C and Lah, JJ and Levey, AI and Johnson, ECB},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103553},
doi = {10.1002/alz70856_103553},
pmid = {41452865},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/blood ; *Alzheimer Disease/blood/genetics/pathology ; Male ; Female ; Aged ; Cohort Studies ; *Amyloidosis/blood ; Proteome/metabolism ; Brain/pathology/metabolism ; Cognitive Dysfunction/blood ; Blood Proteins/metabolism ; Aged, 80 and over ; Apolipoprotein E4/genetics ; },
abstract = {BACKGROUND: Clinical Alzheimer's disease (AD) is currently characterized by cerebral β-amyloidosis associated with cognitive impairment. However, most cases of AD are associated with multiple neuropathologies at autopsy. The peripheral protein changes associated with these AD endophenotypes are poorly understood.

METHOD: We analyzed the plasma proteomes of individuals from four cohorts (n = 2,103 participants) to identify proteins and pathways associated with cerebral β-amyloidosis and cognitive function, as well as multiple other neuropathologies commonly associated with AD.

RESULT: Plasma proteins positively associated with cerebral β-amyloidosis were enriched in synaptic and extracellular matrix (ECM) pathways, whereas proteins negatively associated with amyloidosis were enriched in metabolism and proteostasis pathways. Many proteins strongly associated with cerebral β-amyloidosis were influenced by APOE ε4 genotype. Proteins positively associated with cognitive function were enriched in protein translation, vesicular transport, and mitochondrial pathways whereas proteins negatively associated with cognitive function were enriched in inflammation, fatty acid metabolism, and ECM pathways. Analyses in a cohort with paired brain data showed that known neuropathologies could account for only half of proteins associated with cognitive function, and that many plasma proteins associated with these neuropathologies are not strongly correlated to levels in brain.

CONCLUSION: Multiple biological pathways and processes associated with cerebral β-amyloidosis, cognitive function, and other AD endophenotypes can be observed in plasma, some of which are likely influenced by peripheral factors. Therapeutic approaches targeting these pathways in the central nervous system or the periphery may modify AD risk or disease progression.},
}

Humans
*Biomarkers/blood
*Alzheimer Disease/blood/genetics/pathology
Male
Female
Aged
Cohort Studies
*Amyloidosis/blood
Proteome/metabolism
Brain/pathology/metabolism
Cognitive Dysfunction/blood
Blood Proteins/metabolism
Aged, 80 and over
Apolipoprotein E4/genetics

@article {pmid41452810,
year = {2025},
author = {Tristão-Pereira, C and Baena, AY and Londono, N and Vasquez, D and Alcina, J and Martinez, L and Alvarez, S and Vidal, M and Niño, DFA and Sanchez, JS and Malotaux, V and He, B and Giudicessi, A and Medrano, R and Gatchel, JR and Hanseeuw, BJ and Quiroz, YT},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103502},
doi = {10.1002/alz70856_103502},
pmid = {41452810},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Biomarkers/metabolism ; *Alzheimer Disease/genetics/diagnostic imaging/metabolism ; Positron-Emission Tomography ; Adult ; *Cognitive Dysfunction/diagnostic imaging/genetics/metabolism ; Middle Aged ; Presenilin-1/genetics ; Fluorodeoxyglucose F18 ; *Brain/diagnostic imaging/metabolism ; tau Proteins/metabolism ; Mutation/genetics ; Colombia ; Neuropsychological Tests ; Glucose/metabolism ; Amyloid beta-Peptides/metabolism ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms, affecting 60%-90% of dementia patients, are increasingly recognized early manifestations of disease. Mild behavioral impairment (MBI) is an emerging construct characterized by decreased motivation, affective dysregulation, disinhibition and perceptual changes in non-demented individuals that has shown inconsistent associations with neurodegeneration. This study investigates the relationship between MBI and cerebral glucose metabolism, a marker of neuronal and astrocytic degeneration, in autosomal-dominant Alzheimer's disease (AD).

METHOD: Participants from the Colombia-Boston (COLBOS) Biomarkers Study (Table 1), including 22 Presenilin-1 E280A mutation carriers (40.2±6.9 years, 15 females, 5 cognitively impaired) and 26 cognitively unimpaired non-carriers (38.4±5.7 years, 18 females) completed the self-reported MBI-Checklist (MBI-C). They were classified as MBI- (MBI-C=0) and MBI+ (MBI-C>0). Working memory was assessed using the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning. Cerebral glucose metabolism in the precuneus was measured using [18]F-fluorodeoxyglucose (FDG) PET. Group comparisons were performed using the Wilcoxon rank-sum test. In a subsample with amyloid ([11]C-Pittsburgh compound B) and tau ([18]F-flortaucipir) PET, a mediation analysis tested whether the association between MBI and FDG uptake was mediated by AD pathology (latent variable defined as amyloid and tau).

RESULT: The prevalence of MBI positivity was higher in carriers (68%), compared to non-carriers (35%) (p = 0.041). Groups did not differ in working memory (p = 0.060), although MBI+ carriers tended to have lower performance. Among the whole sample, MBI+ participants had lower precuneus FDG uptake (p = 0.019) than MBI-. This difference was mainly driven by MBI+ carriers, which had lower FDG uptake than MBI- carriers (p = 0.026), while no differences were found between MBI groups among non-carriers. The association between MBI and FDG uptake was partially (70%) mediated by AD pathology (indirect effect: b=-0.600, p = 0.011).

CONCLUSION: Mutation carriers with MBI exhibited hypometabolism in an early AD-related region, partially explained by AD pathology; however, no memory performance differences were observed. These findings suggest that MBI may serve as a risk factor for disease progression, with neuropsychiatric symptoms potentially preceding both neurodegeneration and cognitive impairment. Expanding the sample size will be essential to strengthen the evidence and further investigate MBI as a promising marker for identifying high-risk individuals who may benefit from prevention strategies.},
}

Humans
Female
Male
Biomarkers/metabolism
*Alzheimer Disease/genetics/diagnostic imaging/metabolism
Positron-Emission Tomography
Adult
*Cognitive Dysfunction/diagnostic imaging/genetics/metabolism
Middle Aged
Presenilin-1/genetics
Fluorodeoxyglucose F18
*Brain/diagnostic imaging/metabolism
tau Proteins/metabolism
Mutation/genetics
Colombia
Neuropsychological Tests
Glucose/metabolism
Amyloid beta-Peptides/metabolism

@article {pmid41452807,
year = {2025},
author = {Peiris, S and Yang, Q and Mudiyanselage, AME and Elyan, R and Geesey, K and Kanekar, S and Will, J and Eslinger, P and Karunanayaka, P},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103885},
doi = {10.1002/alz70856_103885},
pmid = {41452807},
issn = {1552-5279},
mesh = {Humans ; Positron-Emission Tomography ; Male ; Female ; *Alzheimer Disease/diagnostic imaging/metabolism ; Aged ; *Amyloid beta-Peptides/metabolism ; Neuropsychological Tests ; Biomarkers/metabolism ; *Cognitive Dysfunction/diagnostic imaging/metabolism ; *Brain/diagnostic imaging/metabolism ; Magnetic Resonance Imaging ; Middle Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Amyloid imaging with positron emission tomography (PET) is important for the diagnosis and treatment of Alzheimer's disease (AD). Probable AD is typically diagnosed with magnetic resonance imaging (MRI) by identifying anatomical changes unique to AD. Due to natural variations in brain volume, structural MR imaging is rather ambiguous. The standardized uptake value ratio (SUVr), derived from PET imaging, is a more accurate quantitative measure for accurate diagnosis of AD. Furthermore, cognitive decline and olfactory impairment are common preclinical symptoms of AD. To better understand brain-behavior relationships in AD spectrum, here we explored relationships with SUVr and behavioral (neuropsychological/olfactory) test scores. We hypothesized that there will be negative correlations between neuropsychological test scores and SUVR values.

METHOD: We analyzed Amyloid beta PET (Aβ) scans from 44 subjects (19 CN, 25 MCI). PET scans were conducted on a Siemens Biograph mCT 20 scanner with 10-minute scans taken 30 minutes post-injection. The images were pre-processed and registered to T1 MRI. Standardized Uptake Value Ratio (SUVr) was calculated with Clinica software. Correlation analyses was performed with DPABI software.

RESULT: Significant group differences in neuropsychological scores were observed between CN and MCI (Figure 1), were observed between CN and MCI figure. Similarly, SUVr differences were observed between CN and MCI (Figure 2). The impact of SUVr on various cognitive domains in terms of correlation analyses were investigated and shown in Figure 3. All correlations yielded highly significant results at p <0.005.

CONCLUSION: This study provides valuable insights into the relationship between Aβ PET imaging and cognitive function in both the (CN) and (MCI) subjects. The correlation between SUVr and olfactory function was insignificant. Olfactory measures such as Identification and Threshold may require further improvement to enhance their utility in AD pathophysiology. Overall, our findings show that higher amyloid beta deposition is linked to poorer cognitive performance in MCI. Our results may offer potential avenues to streamline the Neuropsychological test battery for AD by closely tying most salient metrics to amyloid beta deposition.},
}

Humans
Positron-Emission Tomography
Male
Female
*Alzheimer Disease/diagnostic imaging/metabolism
Aged
*Amyloid beta-Peptides/metabolism
Neuropsychological Tests
Biomarkers/metabolism
*Cognitive Dysfunction/diagnostic imaging/metabolism
*Brain/diagnostic imaging/metabolism
Magnetic Resonance Imaging
Middle Aged
Aged, 80 and over

@article {pmid41452798,
year = {2025},
author = {Paruchuri, N and Jacoby, JR and Salat, DH},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e102768},
doi = {10.1002/alz70856_102768},
pmid = {41452798},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/pathology/diagnostic imaging ; *Cognitive Dysfunction/pathology/diagnostic imaging ; Aged ; *Biomarkers ; *White Matter/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Disease Progression ; *Brain/pathology/diagnostic imaging ; Neuroimaging ; Aged, 80 and over ; Neuropsychological Tests ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is defined by a distinct neuropathological signature, yet symptom severity can vary among individuals with similar levels of pathology. For example, some individuals with the same degree of AD pathology exhibit severe dementia, while others retain relatively higher cognitive function, a phenomenon referred to as cognitive resilience. However, the mechanisms underlying this resilience require further investigation. Microvascular pathology, measured as white matter hyperintensities (WMH), typically considered independent of primary AD pathology, has been shown to influence disease progression. However, previous studies have not examined the impact of WMH after accounting for regional variation in neurodegeneration.

METHOD: We leveraged data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the role of WMH in cognitive status and resilience and the progression from mild cognitive impairment (MCI) to AD. Individuals with a baseline diagnosis of MCI were selected and stratified by sex (n = 413-442 depending on the analysis). Within sex, participants were stratified into 'high' and 'low' cognitive performance groups using the ADNI cognitive composite scores based on residuals from cognition and individual brain region volume relationships after adjusting for age. Temporal regions were analyzed in relation to memory performance (ADNI-Mem), while frontal regions were analyzed in relation to executive functioning (ADNI-EF2). Analyses were conducted separately for men and women.

RESULT: There was a significant difference in WMH volume in 'high' compared to 'low' performance groups in men but not in women. Effects remained after accounting for age and the volumes of temporal and frontal brain regions. In both men and women, individuals in the 'low' performance groups had significantly greater probability of AD conversion across the longitudinal interval.

CONCLUSION: These results suggest a sex difference, with WMH burden serving as a stronger predictor of baseline cognitive status and AD conversion in men than in women. The findings also indicate that microvascular disease, quantified as WMH, contributes to cognitive variation with lower WMH being associated with greater resilience in MCI-to-AD progression beyond structural integrity. These results highlight the crucial role of vascular health in preserving functional independence in individuals with AD pathology.},
}

Humans
Male
Female
*Alzheimer Disease/pathology/diagnostic imaging
*Cognitive Dysfunction/pathology/diagnostic imaging
Aged
*Biomarkers
*White Matter/pathology/diagnostic imaging
Magnetic Resonance Imaging
Disease Progression
*Brain/pathology/diagnostic imaging
Neuroimaging
Aged, 80 and over
Neuropsychological Tests

@article {pmid41452781,
year = {2025},
author = {Kulczynska-Przybik, A and Krawczuk, D and Borawska, R and Winkel, I and Mroczko, B},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103793},
doi = {10.1002/alz70856_103793},
pmid = {41452781},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/cerebrospinal fluid/blood ; *Biomarkers/cerebrospinal fluid/blood ; *tau Proteins/cerebrospinal fluid/blood ; *Chemokine CXCL1/cerebrospinal fluid/blood ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Multiple investigations on the pathological mechanisms of Tau protein in the course of Alzheimer's disease (AD) have been carried out, however, the exact processes are still unclear. One of the crucial factors contributing to the development of AD seems to be chemokine CXCL1 produced by neurons and cells of the immunological system in the brain. It was reported that monocytes from AD patients express significantly elevated levels of CXCL1, additionally, this chemokine is involved in monocyte migration from the blood to the brain in AD patients. Furthermore, some evidence from studies performed on neuronal lines and animal models indicates that CXCL1 contributes to caspase-3-dependent tau cleavage, which may result in abnormal distribution of the tau protein. In pathological conditions, CXCL1 activates the CXCR2 receptor on neurons, which causes the activation of pathways and leads to the hyperphosphorylation of tau. Therefore, we aimed to assess the CXCL1 levels in CSF patients with AD and cognitively normal subjects and compared them with CSF and plasma indicators of tau protein pathology.

METHOD: The concentrations of CXCL1 as well as neurochemical dementia biomarkers were measured in cerebrospinal fluid and plasma patients with AD and patients without cognitive decline by multiplexing, SIMOA, and enzyme-linked immunosorbent techniques.

RESULT: Significantly higher CSF concentrations of CXCL1 were found in AD patients compared to the subjects without cognitive decline. Furthermore, in the group of patients with AD, the levels of CXCL1 significantly correlated with CSF pTau181 protein. Similarly, a significant association between CSF CXCL1 and Tau plasma protein was observed.

CONCLUSION: Our findings indicate that CXCL1 may play a role in the pathogenesis of AD, particularly in the intensified mechanism of Tau protein.},
}

Humans
*Alzheimer Disease/cerebrospinal fluid/blood
*Biomarkers/cerebrospinal fluid/blood
*tau Proteins/cerebrospinal fluid/blood
*Chemokine CXCL1/cerebrospinal fluid/blood
Male
Female
Aged
Middle Aged
Aged, 80 and over

@article {pmid41452770,
year = {2025},
author = {Herring, CH and Butts, B and Higgins, M and Watson, J and Brewster, GS and Wharton, W and Gary, R and Hepburn, K and Dunbar, SB},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e106566},
doi = {10.1002/alz70858_106566},
pmid = {41452770},
issn = {1552-5279},
mesh = {Humans ; *Caregivers/psychology/education ; Male ; Female ; *Dementia/nursing/psychology ; Aged ; Adaptation, Psychological ; *Stress, Psychological/therapy/psychology ; Middle Aged ; Black or African American/psychology ; Aged, 80 and over ; White ; },
abstract = {BACKGROUND: Black caregivers of persons living with Alzheimer's disease and related dementias (ADRD) experience significant health disparities, including elevated cardiovascular risk and high stress levels. This study evaluates the effects of a culturally tailored psychoeducational intervention, with and without exercise, on caregiver health, stress, and coping.

METHOD: In this randomized controlled trial (NCT01188070), 142 Black caregivers were assigned to one of three groups: attention control, psychoeducation, or psychoeducation plus exercise. The psychoeducational intervention, The Great Village, focused on culturally relevant caregiving strategies, while the exercise component included a home-based walking and resistance program. Outcomes assessed at baseline and six months included cardiovascular risk markers, perceived stress, and coping. Group differences were analyzed using ANCOVA, adjusting for baseline values.

RESULT: The psychoeducation group showed significant reductions in diastolic blood pressure (p = 0.034) and blood glucose (p = 0.021). Both intervention groups reported lower perceived stress (p = 0.048). However, the psychoeducation plus exercise group did not demonstrate expected improvements in physical function or cardiovascular risk and showed a decline in positive reappraisal coping (p = 0.048).

CONCLUSION: Culturally tailored psychoeducation may improve cardiovascular risk and stress outcomes in Black dementia caregivers. The added exercise component did not yield additional benefits, suggesting the need for alternative strategies to enhance physical activity in this population. Future research should explore longer-duration interventions and ways to support exercise adherence within the context of caregiving.},
}

Humans
*Caregivers/psychology/education
Male
Female
*Dementia/nursing/psychology
Aged
Adaptation, Psychological
*Stress, Psychological/therapy/psychology
Middle Aged
Black or African American/psychology
Aged, 80 and over
White

@article {pmid41452767,
year = {2025},
author = {Wong, E and Lee, LY and Montagnese, M and Kourtzi, Z and Rittman, T},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103689},
doi = {10.1002/alz70856_103689},
pmid = {41452767},
issn = {1552-5279},
mesh = {Humans ; *Frontotemporal Dementia/diagnostic imaging/diagnosis/classification ; *Machine Learning ; *Biomarkers ; Male ; Female ; Neuroimaging ; Disease Progression ; Magnetic Resonance Imaging ; Aged ; Algorithms ; Middle Aged ; Brain/diagnostic imaging ; Alzheimer Disease ; },
abstract = {BACKGROUND: Frontotemporal dementia (FTD) is characterized by a decline in cognitive capabilities including behavior, judgment and language. Classically, FTD is divided into three subtypes: behavioural variant (bvFTD), semantic variant (SD), and non-fluent variant (nfvPPA). FTD and its subtypes often go misdiagnosed, emphasizing the need for robust computational tools that can more accurately diagnose/subtype the disease and characterize an individual's likely disease progression. Very little work has been done in developing clinically translatable machine learning (ML) tools to model FTD, with many currently available diagnostic and prognostic algorithms relying on non-continuous metrics and clinical labels instead of capturing information in longitudinal patient trajectories.

METHOD: We aimed to address these limitations by developing and validating a trajectory modeling approach that allows for enhanced characterization of an individual's cognitive progression. Specifically, we extended a Generalized Matrix Learning Vector Quantization (GMLVQ) machine learning algorithm previously successfully applied to Alzheimer's disease, optimizing and implementing it for FTD. We trained our models on the Neuroimaging in Frontotemporal Dementia (NIFD) dataset, comprising 288 FTD patients and 118 controls with baseline and longitudinal clinical, cognitive, and neuroimaging data (T1 weighted structural MRI). Utilizing Freesurfer, we extracted segmentation and parcellation data containing cortical thicknesses and volumes in all major cortical and subcortical regions yielding ∼180 neuroimaging features for modeling.

RESULT: Our initial binary classification GMLVQ models for SD versus bvFTD/nfvPPA achieved a 94.4% accuracy. Areas like the left hemispheric (LH) temporal pole, the LH inferior, middle, and superior temporal gyri, and the LH fusiform gyrus appeared to be most influential in the model's decision. Extending our GMLVQ model towards the multi-class classification of all three subtypes, we achieved a 79.9% accuracy, with most misclassifications relating to differentiating bvFTD and nfvPPA patients. Finally, to probe our GMLVQ model architecture's prospective performance amongst a broader neurodegenerative disease dataset, we fit a six-class classifier for each FTD subtype alongside Alzheimer's disease, mild cognitive impairment, and control patient data (dervied from ADNI4), achieving an accuracy of 52.2%.

CONCLUSION: Further model tuning for the multi-class model is most needed; however, these preliminary results suggest that GMLVQ trajectory modeling shows promise for advancing the diagnosis and assessment of FTD.},
}

Humans
*Frontotemporal Dementia/diagnostic imaging/diagnosis/classification
*Machine Learning
*Biomarkers
Male
Female
Neuroimaging
Disease Progression
Magnetic Resonance Imaging
Aged
Algorithms
Middle Aged
Brain/diagnostic imaging
Alzheimer Disease

@article {pmid41452752,
year = {2025},
author = {Zhang, L and Silva-Rodríguez, J and Alfayate, E and Wagner, S and Sanchez-Juan, P and Grothe, MJ},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104410},
doi = {10.1002/alz70856_104410},
pmid = {41452752},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Aged ; *Biomarkers/blood ; *tau Proteins/blood ; *Alzheimer Disease/blood/pathology ; Aged, 80 and over ; Longitudinal Studies ; Cross-Sectional Studies ; Diffusion Magnetic Resonance Imaging ; Magnetic Resonance Imaging ; Brain/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: Plasma ptau217 has recently emerged as a reliable biomarker for early Alzheimer's disease (AD) pathology. Additionally, previous works have suggested that indices of cortical mean diffusivity (MD) derived from diffusion-weighted imaging are thought to reflect early microstructural changes preceding detectable structural atrophy in neurodegenerative diseases. While ptau217 has been shown to correlate with cortical atrophy in cognitively normal individuals, its relationship with cortical MD remains unstudied.

METHODS: 1029 cognitively unimpaired (CU) elderly participants (mean age: 74.9, range: 69-87; 65% female) with 3T MRI and plasma ptau217 measures were selected for baseline cross-sectional analyses from the Vallecas Project cohort, a single-centre 12-year longitudinal study with annual follow-ups. Plasma ptau217 levels were measured on the fully automated LUMIPULSE platform, and individuals were classified as either ptau217+ (n = 174, mean age: 76.0) or ptau217- (n = 855, mean age: 74.7) based on a pre-established threshold of 0.247 pg/mL. Diffusion-weighted images were preprocessed using an in-house pipeline to correct for eddy currents and image distortions due to magnetic field inhomogeneity, and diffusion tensors were fitted using FSL. A normalised grey matter image was used to mask normalised MD images to obtain cortical grey matter MD maps, which were subsequently analysed in a voxel-wise GLM using SPM12, controlling for age and sex.

RESULTS: At baseline, there was no difference between groups in sex distribution, although individuals with elevated ptau217 levels were significantly older (p = 0.0001). After controlling for sex and age, the ptau217+ group showed significantly higher cortical MD in bilateral medial temporal (amygdala and hippocampus) and insular regions (insular and opercular cortices) compared to ptau217- (p <0.05, FDR-corrected; Figure 1).

CONCLUSIONS: In our study of a large-scale, well-characterised cognitively unimpaired population with available diffusion weighted imaging, changes in cortical MD can already be observed in those with elevated plasma ptau217 in regions commonly associated with AD neuropathology. Further analysis on longitudinal MD changes in the same cohort are ongoing.},
}

Humans
Female
Male
Aged
*Biomarkers/blood
*tau Proteins/blood
*Alzheimer Disease/blood/pathology
Aged, 80 and over
Longitudinal Studies
Cross-Sectional Studies
Diffusion Magnetic Resonance Imaging
Magnetic Resonance Imaging
Brain/pathology/diagnostic imaging

@article {pmid41452745,
year = {2025},
author = {Konofagou, E},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103290},
doi = {10.1002/alz70856_103290},
pmid = {41452745},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/therapy/metabolism ; *Blood-Brain Barrier/diagnostic imaging ; Biomarkers/metabolism ; Microbubbles ; Male ; Female ; Glioma/diagnostic imaging/therapy ; Middle Aged ; Animals ; Adult ; Aged ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Treatment of neurological diseases has been at the forefront of medical research for more than a century with limited success due partly to the blood-brain barrier (BBB) that impedes both delivery and biodistribution of the drug delivered. Focused ulltrasound (FUS) methodologies in conjunction with systemically administered microbubbles have been shown capable of transcranially and transiently opening the BBB over the past two decades. More recently, those efforts have resulted into clinical translation in a variety of brain diseases such as brain tumors and neurodegenerative diseases such as Alzheimer's (AD) disease. Most FUS systems that have been reported for AD treatment are either confined in the MRI or use invasively implanted transducers. Our group has pioneered a portable system for opening the BBB at the patient's bedside safely and efficiently, i.e., within 20-30 min with real-time cavitation mapping.

METHOD: Five AD patients underwent FUS with microbubbles for transcranial BBB opening in their prefrontal cortex. Real-time cavitation mapping system was also implemented to transcranially map the cavitation occurrence and dose in real time throughout the BBB opening procedure in Alzheimer's disease (AD) adult and diffuse intrinsic pontine glioma (DIPG) pediatric patients. Passive acoustic mapping (PAM) with coherence factor (CF) correction is used to passively map the microbubble activity within the brain. Multi-element CF-PAM allows us to determine the exact location of the BBB opening. The system was first optimized in targeting in non-human primates followed by feasibility in the prefrontal cortex in AD patients, achieving feedback rates of 2 Hz during the clinical procedures.

RESULT: It was found that 60% of the patients exhibited beta amyloid reduction as evidenced by the SUVr reduction on PET imaging. We also found that cavitation dose can inform the beta amyloid reduction with 80% correlation between the cavitation dose and SUVRr reduction observed.

CONCLUSION: A portable FUS system was found to be safe and efficacious in reduction of beta amyloid in patients with mild to moderate AD. Real-time information on cavitation can provide feedback on both the safety and efficacy of treatment. Future studies will investigated effects on cognition and tau reduction.},
}

Humans
*Alzheimer Disease/diagnostic imaging/therapy/metabolism
*Blood-Brain Barrier/diagnostic imaging
Biomarkers/metabolism
Microbubbles
Male
Female
Glioma/diagnostic imaging/therapy
Middle Aged
Animals
Adult
Aged
Magnetic Resonance Imaging

@article {pmid41452744,
year = {2025},
author = {Zhang, J and Ji, Y and Liu, J and Cui, W and Yao, X and Li, H and Zhang, D and Du, L and , },
title = {Mutual Learning for Joint Disease Detection and Severity Prediction Reveals Multimodal Pathogenesis for Neurodegenerative Disorders.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btaf629},
pmid = {41452744},
issn = {1367-4811},
abstract = {MOTIVATION: Neurodegenerative disorders influence millions of people worldwide, and uncovering the pathogenesis is of urgent need. Many efforts have been made to detect or predict neurodegenerative disorders, while exploring the pathogenesis has been ignored from a systemic perspective.

RESULTS: To handle this issue, we propose a novel and powerful method, referred to as Pathogenesis-aware Mutual-Assistance Classification and Regression Optimization (Pa-MACRO). First, Pa-MACRO incorporates a mutual-assistance bidirectional mapping technique with a joint-embedding fine-grained interpretability module. This can extract the intrinsic factors and their interactions of multimodal pathogenesis. Second, our method can simultaneously classify an at-risk individual and predict the severity triggered by neurodegenerative disorders. Furthermore, to address the small sample size issue and the high-dimensional issue, we meticulously incorporate a semi-supervised cooperative learning method to integrate unlabeled data and extend it to a chromosome-wide setting in the spirit of divide-and-conquer. The Alzheimer's Disease Neuroimaging Initiative (ADNI) database was used to evaluate Pa-MACRO. Without bells and whistles, Pa-MACRO establishes new state-of-the-art results in various settings while maintaining superior interpretability, verifying its power and versatility in revealing the pathogenesis of neurodegenerative disorders.

The software is publicly available at https://github.com/ZJ-Techie/Pa-MACRO.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid41452736,
year = {2025},
author = {Martin, SA and Biondo, F and Jewell, A and Barkhof, F and Cole, JH},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e102951},
doi = {10.1002/alz70856_102951},
pmid = {41452736},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Magnetic Resonance Imaging ; *Alzheimer Disease/diagnostic imaging/diagnosis ; Aged ; *Biomarkers ; Neuroimaging/methods ; Aged, 80 and over ; *Dementia/diagnostic imaging ; Brain/diagnostic imaging ; *Artificial Intelligence ; },
abstract = {BACKGROUND: Existing applications of artificial intelligence for dementia prediction have largely relied on the use of large, curated research datasets for developing and evaluating model performance. Despite reported high accuracies, a significant gap remains in assessing their generalisability to real-world data.

METHOD: 3D T1-weighted magnetic resonance imaging scans were extracted from the South London and Maudsley Hospital (SLaM) NHS Trust and linked with de-identified electronic health records via the Clinical Record Interactive Search database. This was used to identify 1140 individuals (self-reported ethnicities: 19.7% Black/African/Caribbean, 11.0% Asian, 58.4% British/White, 10.4% Mixed/Other/Unknown) who received a scan at least 3 months prior to a dementia diagnosis or had a scan but no record of dementia (Biondo 2022, NeuroImage: Clinical). 3D ResNet models were trained using MRI from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative, to classify individuals with Alzheimer's disease dementia from cognitively unimpaired individuals. First, the trained models were used to classify dementia patients from those with no dementia in the SLaM cohort using MRI only. Then, imaging-based model probabilities of Alzheimer's disease dementia (pAD) were combined with covariates of age, sex and MMSE score in a Cox proportional hazards (Cox-PH) regression model to estimate the time between the scan and recorded diagnosis. Data was right-censored to account for individuals with no record of dementia.

RESULT: Classification accuracies ranged from 65.3%-68.6% as shown in Table 1. The hazard ratios for each covariate are summarised in Table 2. The pAD hazard ratios [95% CI] were 3.58 [2.79,4.61], 4.67 [3.46,6.30] and 4.35 [3.34,5.67] for models trained on NACC, ADNI and both datasets respectively, and were all statistically significant (α=0.0017). Kaplan Meier curves and Cox-PH partial effect plots for pAD are shown in Figure 1.

CONCLUSION: Models trained on large, research cohorts are effective at predicting progression to dementia for real-world NHS patients, despite differences in the sample characteristics. pAD was significant at estimating time-to-diagnosis, with a 0.1 increase in pAD equating to a 13.6%-16.7% increased risk of receiving a dementia diagnosis within 8 years. These findings demonstrate the clinical utility of generalisable artificial intelligence models in a real-world context.},
}

Humans
Male
Female
Magnetic Resonance Imaging
*Alzheimer Disease/diagnostic imaging/diagnosis
Aged
*Biomarkers
Neuroimaging/methods
Aged, 80 and over
*Dementia/diagnostic imaging
Brain/diagnostic imaging
*Artificial Intelligence

@article {pmid41452735,
year = {2025},
author = {Machado, LS and Povala, G and Pola, I and Vizlin-Hodzic, D and Rosa-Neto, P and Zimmer, ER and Blennow, K and Zetterberg, H and Ashton, NJ and Benedet, AL},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e103748},
doi = {10.1002/alz70856_103748},
pmid = {41452735},
issn = {1552-5279},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid/diagnostic imaging ; *Parkinson Disease/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Male ; Female ; Aged ; alpha-Synuclein/cerebrospinal fluid ; *Neuroglia/metabolism ; Cohort Studies ; *Cognitive Dysfunction/cerebrospinal fluid ; Proteomics ; Positron-Emission Tomography ; },
abstract = {BACKGROUND: Glial cells play important roles in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Glial dysfunction is thought to contribute to neurodegeneration progression, but a few cerebrospinal fluid (CSF) biomarkers effectively capture these changes. Identifying novel glial-derived CSF biomarkers may improve our understanding of AD and PD pathology and aid in disease monitoring.

METHOD: We selected astrocyte-, oligodendrocyte-, oligodendrocyte precursor cell (OPC)-, and microglia-enriched and enhanced genes from single-cell and single-nucleus transcriptomic datasets. These gene lists were cross-referenced with CSF proteomic data (SomaLogic) from two AD cohorts (cohorts 1 and 2) and a PD cohort (cohort 3) (Figures 1-3ADF). Linear regression models were used to assess differential protein expression in CSF between cognitively unimpaired (CU) and cognitively impaired (CI) individuals, as well as between amyloid-beta (Aβ)-positive and alpha-synuclein (α-syn)-positive individuals, within each glial cell type. In cohorts 1 and 3, differentially abundant proteins were clustered based on their pseudo-progression across CU and CI individuals, further stratified by Aβ (pTau181/Aβ42 ratio cut-off=0.028) or α-syn status. In a subset of cohort 1, voxelwise analyses examined associations between protein cluster averages and [[18]F]Florbetapir-PET amyloid imaging, adjusting for age and sex. Random field theory (RFT) was applied for multiple comparison correction in imaging analyses.

RESULT: We identified 47 astrocyte-, 94 oligodendrocyte/OPC-, and 94 microglia-related proteins that were significantly altered in CI individuals compared to CU. In Aβ+ individuals, 52 astrocyte- (Figure 1BE), 99 oligodendrocyte/OPC- (Figure 2BE), and 117 microglia-related proteins (Figure 3BE) were differentially expressed. Similarly, in α-syn+ individuals, 143 glial proteins were altered across astrocytes, oligodendrocytes/OPCs, and microglia (Figures 1-3G). Clustering analysis categorized proteins into four distinct groups per cell type and cohort (Figures 1-3CH). In cohort 1, voxelwise analyses demonstrated that at least one cluster per cell type presented an association with [[18]F]Florbetapir-PET imaging, particularly in cortical gray matter (data not shown).

CONCLUSION: This study identified 485 glial-related CSF proteins altered in AD or PD. We also uncovered distinct glial protein clusters across AD pseudo-progression and their association with Aβ burden in the brain, highlighting potential glial biomarkers for neurodegenerative disease progression. These findings can help uncover the glial heterogeneity present in AD and PD.},
}

Humans
*Biomarkers/cerebrospinal fluid
*Alzheimer Disease/cerebrospinal fluid/diagnostic imaging
*Parkinson Disease/cerebrospinal fluid
Amyloid beta-Peptides/cerebrospinal fluid
Male
Female
Aged
alpha-Synuclein/cerebrospinal fluid
*Neuroglia/metabolism
Cohort Studies
*Cognitive Dysfunction/cerebrospinal fluid
Proteomics
Positron-Emission Tomography

@article {pmid41452730,
year = {2025},
author = {Honig, LS and Gonzalez, WP and Kim, JM and DiMuro, V and Bell, KL and Jagannathan, R and Noble, JM and Marder, K and Mayeux, R},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e107460},
doi = {10.1002/alz70858_107460},
pmid = {41452730},
issn = {1552-5279},
mesh = {Humans ; Aged ; Female ; Male ; Aged, 80 and over ; Middle Aged ; Adult ; *Alzheimer Disease/drug therapy/psychology ; *Dementia/drug therapy/psychology ; },
abstract = {BACKGROUND: Lecanemab and donanemab are anti-amyloid antibodies proven in 18-month clinical trials to slow progression of early Alzheimer's disease by biomarker, cognitive and functional measures. While both are now approved in many countries, lecanemab was first USA-approved in January2023, and Medicare-covered since July2023. Early-AD patients are receiving therapy, but drug access has been limited by barriers, many imposed by use recommendations, and by insurer-payor criteria. These partly reflect attempts to apply clinical trial exclusions to early AD patients, and concerns over adverse-effect rates that might occur with widespread use.

METHOD: We report, with IRB-approval, our practice experience, prescribing on-label, without other limitations, in >190 diverse patients, age 35-90, using various infusion and MRI facilities. Patients all had amyloid confirmation by CSF (72%), amyloid-PET (15%), or both (14%); 89% have accepted optional APOE-genotyping, with 41% non-carriers, 46% E4-heterozygotes, and 13% E4-homozygotes.

RESULT: Patients have had 1-40 biweekly infusions. Adverse event rates have been similar to those in clinical trials with 15% infusion reactions (headache, chills, warmth, fatigue, pruritus), usually only at first 1-3 infusions. Overall rate of ARIA-E has been 10.6% (mostly in first 3 months), with 2 of 20 cases recurrent, and with a lower incidence of ARIA-H. Only 2 patients (1%) have had symptomatic ARIA, both ARIA-E, an E4 heterozygote with cortical visual loss, and an E4 homozygote with aphasia, both with concurrent mild ARIA-H. The latter individual unfortunately died during ICU treatment for refractory focal status epilepticus; this was the only death. Most ARIA cases have resumed infusions after resolution; overall, there was discontinuation of therapy in 9% of treated patients (4% due to ARIA, 2% due to persistent infusion reactions, 3% due to disinterest).

CONCLUSION: Our single-site findings suggest that "real-world" experience with lecanemab may be not dissimilar to that in clinical trials, and that despite a small risk of unavoidable serious adverse events, there can be ease of administration and MRI procedures, good tolerability, and relative safety. It is appropriate to use extant clinical evidence, and biological plausibility, rather than provide barriers to access, in discussing potential risks and benefits, and providing access to patients and their families.},
}

Humans
Aged
Female
Male
Aged, 80 and over
Middle Aged
Adult
*Alzheimer Disease/drug therapy/psychology
*Dementia/drug therapy/psychology

@article {pmid41452722,
year = {2025},
author = {Simon, L and Stephan, A and Sardina, AL and Meadows, J and Hampton, M and Ross, LA and Gamaldo, AA},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e105547},
doi = {10.1002/alz70858_105547},
pmid = {41452722},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; Aged ; Aged, 80 and over ; Middle Aged ; *Dementia/psychology/therapy/ethnology ; Black or African American/psychology ; South Carolina ; Focus Groups ; *Family/psychology ; Decision Making ; *Caregivers/psychology ; White ; },
abstract = {BACKGROUND: The prevalence of Alzheimer's disease and related dementias (ADRD) in South Carolinians is expected to increase by over 26% between 2020-2025, making South Carolina a priority state for ADRD-related health research. The effects of ADRD impact both individuals experiencing cognitive decline and their families and communities. Family members and close friends are often involved in healthcare decisions; this may be exceedingly true for minoritized populations, such as Black/African American families, who can have limited access to resources but abundant cultural capital. Despite this, multigenerational family processes are rarely considered in minority aging research. To address this challenge, we conducted an investigation to identify beliefs, expectations, and relevant factors in families' discussions and decision- making around ADRD-related topics.

METHOD: Our sample included 40 South Carolinians (Mage=70.25, SD=10.00, range=45-89 years, 82.5% Women, 97.5% Black/African American) from two churches. We employed a mixed methods approach that emphasized the qualitative strand. Participants engaged in a facilitated focus group discussion with family members/fictive kin, and independently responded to quantitative measures at three time points (pre-focus group, one-week post-focus group, and one month post-focus group) via an online survey. Preliminary analyses included thematic analysis of focus group responses and descriptive statistics for ADRD knowledge and perceptions from our one week pre assessments.

RESULT: Findings from the pre-survey demonstrate that 85% of participants believed the focus groups will be helpful for their family and 77.1% felt they were very likely to engage in ADRD conversations with their family. Three notable themes were identified from the focus groups: 1) decisions on caregiving designated to one family member; 2) middle class struggle with medical insurance; and 3) stigma exists pertaining to ADRD caregiving needs. Another meaningful observation was that conceptions of "family" in relation to ADRD discussions, decision making, and support might extend beyond standard relational ties of blood and marriage.

CONCLUSION: This exploratory analysis revealed that focus groups appear to be an acceptable method for promoting discussions and ADRD knowledge/awareness among mid-life and older adult Black/African American South Carolinians and collecting meaningful information about how these conversations are approached within families, friend groups, and communities.},
}

Humans
Female
Male
Aged
Aged, 80 and over
Middle Aged
*Dementia/psychology/therapy/ethnology
Black or African American/psychology
South Carolina
Focus Groups
*Family/psychology
Decision Making
*Caregivers/psychology
White