@article {pmid42483925,
year = {2026},
author = {Li, W and Guo, C and Jin, Y and Ji, H and Zhang, L and Li, W and Zhang, W and Fu, L},
title = {Ganoderma sinense Polysaccharides Improve Cognition in a Mouse Model of Alzheimer's Disease by Modulating Gut Microbiota and Short-Chain Fatty Acid Metabolism.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050473800260622054102},
pmid = {42483925},
issn = {1875-5828},
abstract = {INTRODUCTION: The number of patients with Alzheimer's Disease (AD) worldwide is expected to reach 152 million by 2050, but developing an effective AD treatment remains challenging. This study purified two polysaccharides (GSP1 and GSP2) from Ganoderma sinense, a traditional Chinese medicine, and investigated their potential therapeutic effects against AD.

MATERIALS AND METHODS: GSP1 and GSP2 were purified and characterized for key physicochemical properties, including monosaccharide composition and molecular weight. In vitro neuroprotective efficacy was evaluated using glutamate-challenged SH-SY5Y cells. For in vivo assessment, an AlCl₃/D-galactose induced AD mouse model was established to quantify cognitive/memory enhancement. Multiomic analysis of the gut microbiota, Short-Chain Fatty Acid (SCFAs) metabolomics, and behavioural tests were conducted to elucidate the therapeutic mechanisms of GSP1.

RESULTS: Both GSP1 and GSP2 conferred neuroprotection against toxin-induced damage. Notably, GSP1 demonstrated superior efficacy compared with GSP2, significantly enhancing cognitive/ memory performance and reducing amyloid-β plaque deposition. Furthermore, GSP1 changed gut microbial diversity and SCFA metabolic profiles. Critical genus-level correlations emerged: Turicibacter, Jeotgalicoccus, and Staphylococcus were positively associated with therapeutic outcomes, whereas Odoribacter was negatively associated.

DISCUSSION: Natural polysaccharides, particularly GSP1, demonstrate therapeutic potential against AD by modulating gut microbiota. Mechanistically, this effect is linked to reshaping microbial communities and affecting the production of neuroprotective SCFAs. Although these findings position GSP1 as a promising AD therapeutic candidate, deeper exploration of gut-brain axis mechanisms remains essential for clinical translation.

CONCLUSION: GSP1 emerges as a promising therapeutic candidate for AD, offering a new approach to developing AD-targeted pharmaceuticals and nutraceuticals.},
}

@article {pmid42483984,
year = {2026},
author = {Silva-Rodríguez, J and Zhang, L and Kleineidam, L and López-González, FJ and Wagner-Reguero, S and Martínez-Castillo, M and Sogorb-Esteve, A and Guamán-Chulunchana, ME and Pastor, AB and Moreno, N and Ruiz-Calvo, A and Sánchez-Martín, C and Alfayate, E and Molero-Cartón, M and Valeriano-Lorenzo, EL and Frades-Payo, B and Valentí, M and Zea-Sevilla, MA and Moscoso, A and Ramírez, A and Martino-Adami, P and Riedel-Heller, SG and Scherer, M and Jeromin, A and Calero, M and Del Ser, T and Schneider, A and Grothe, MJ and Sánchez-Juan, P},
title = {Prognostic value of plasma %p-tau217 in cognitively unimpaired older adults.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71599},
pmid = {42483984},
issn = {1552-5279},
support = {//CIEN Foundation/ ; //Reina Sofía Foundation/ ; PI24/00089//Instituto de Salud Carlos III/ ; PI23/01314//Instituto de Salud Carlos III/ ; PMP22/00022//Instituto de Salud Carlos III/ ; RYC2023-043746-Y//Ministerio de Ciencia e Innovación/ ; CNS2024-154295//Ministerio de Ciencia e Innovación/ ; //Hertie Network of Excellence in Clinical Neuroscience/ ; 101155955//European Union's Horizon Europe research and innovation programme/ ; //Cure Alzheimer Foundation/ ; //the Alzheimer Forschung Initiative/ ; NW21-049A-F//Ministry of Culture and Science of the State of North Rhine-Westphalia/ ; //German Ministry of Education and Research/ ; //Verum Foundation/ ; //the Network of University Medicine/ ; //Target ALS/ ; FZK01EK2102A//German Federal Ministry of Education and Research/ ; FZK01GP2213A//German Federal Ministry of Education and Research/ ; FZK 01GP2213A//Bundesministerium für Forschung und Technologie/ ; NW21-049 A-F//Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen/ ; N/A//Cure Alzheimer's Fund/ ; EXC2151-39087304//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *tau Proteins/blood ; Prognosis ; Female ; Disease Progression ; Aged ; Male ; Biomarkers/blood ; *Cognitive Dysfunction/blood/diagnosis ; Dementia/blood/diagnosis ; Phosphorylation ; Longitudinal Studies ; Aged, 80 and over ; },
abstract = {INTRODUCTION: We evaluated the prognostic value of baseline plasma phosphorylated tau 217 ratio (%p-tau217) for predicting long-term progression in cognitively unimpaired (CU) older adults.

METHODS: We analyzed 982 community-dwelling individuals followed annually for up to 12 years. Baseline %p-tau217 levels were quantified by mass spectrometry and stratified into four strata using previously defined cut-offs. Outcomes included longitudinal changes in cognition, neurodegeneration, and progression to mild cognitive impairment (MCI)/dementia. Results were replicated with immunoassays in the same and an independent primary care cohort (n = 1204).

RESULTS: Participants with Elevated/High %p-tau217 exhibited accelerated cognitive decline, hippocampal atrophy, and significantly higher risks of progression to MCI (hazard ratio [HR] > 6.0) and dementia (HR > 9.9). The Low group demonstrated a 92.2% 10-year negative predictive value for any progression.

DISCUSSION: Our results suggest that %p-tau217 is a robust prognostic biomarker, accurately distinguishing CU individuals at minimal risk from those at high risk of future AD-related clinical and neurodegenerative decline. Similar performance was achieved by immunoassays.},
}

Humans
*tau Proteins/blood
Prognosis
Female
Disease Progression
Aged
Male
Biomarkers/blood
*Cognitive Dysfunction/blood/diagnosis
Dementia/blood/diagnosis
Phosphorylation
Longitudinal Studies
Aged, 80 and over

@article {pmid42484400,
year = {2026},
author = {Zawadzki, S and Okła, E and Ortega López, P and de la Mata, FJ and Ionov, M and Kreišmane, M and Skrastiņa, D and Jansons, J and Bryszewska, M and Miłowska, K},
title = {Multilevel Assessment of a Carbosilane Dendrimer-siRNA Nanoplatform: Cellular Compatibility, Blood-Brain Barrier Model Integrity, and Murine Model Biodistribution.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.6c06027},
pmid = {42484400},
issn = {1944-8252},
abstract = {The tight regulation of bidirectional solute flux between the systemic circulation and neural tissue by the blood-brain barrier (BBB) remains a principal obstacle to effective pharmacotherapy of the central nervous system. In this study, we evaluate the biocompatibility and biodistribution of a novel third-generation PEGylated carbosilane dendrimer (G3Si PEG6000) and its siRNA dendriplex with an APOE4-directed siRNA relevant to late-onset Alzheimer's disease using a tiered, upstream strategy that progresses from BBB-relevant monocultures to a capillary-weighted BBB model and in vivo/ex vivo biodistribution in mice, in accordance with current recommendations for nanomaterial testing. In endothelial cells, pericytes, and astrocytes, mitochondrial/redox profiling (MTT, DCF-ROS, and JC-1 ΔΨm) defined tolerated exposure ranges. Complexation with siRNA consistently attenuated apparent cytotoxicity across cell types, yet both free and complexed formulations elicited modest ROS and dose-dependent ΔΨm depolarization, indicating persistent mitochondrial stress. In the BBB model, responses were concentration- and formulation-dependent: 10 µM free dendrimers produced sustained impedance and nuclear confluence loss with sheet-like detachment, whereas the 0.1-2.5 µM free dendrimer and the dendriplex induced transient, recoverable perturbations or increases in impedance and proliferation. In vivo, whole-body IVIS imaging demonstrated prolonged systemic exposure for the dendriplex and an ex vivo kidney-dominant, liver-secondary distribution; no robust dendriplex signal was detected in brain fluorescence by planar NIR-I IVIS under the applied acquisition conditions. Collectively, these data indicate that siRNA complexation broadens the functional window at the BBB model with partially recoverable barrier effects and improved systemic exposure, while not substantially reducing mitochondrial or oxidative stress responses. The results provide a mechanistically informed basis for dose optimization and efficacy testing of this dendrimer-siRNA platform in CNS indications and for advancing this platform in further investigations targeting Alzheimer's disease.},
}

@article {pmid42484409,
year = {2026},
author = {Tulloch, R and Gaffiero, D},
title = {Menopause, brain health and hormone replacement therapy: gaps in knowledge and policy solutions from a Scottish perspective.},
journal = {Post reproductive health},
volume = {32},
number = {1},
pages = {77-81},
doi = {10.1080/20533691.2026.2631221},
pmid = {42484409},
issn = {2053-3705},
mesh = {Humans ; Female ; Scotland ; *Menopause/physiology/psychology ; Women's Health ; *Health Policy ; *Brain/physiology ; *Hormone Replacement Therapy ; Health Knowledge, Attitudes, Practice ; Alzheimer Disease/prevention & control ; Primary Health Care ; Quality of Life ; },
abstract = {PURPOSE: This commentary argues for the systematic integration of brain health into menopause care and policy in the United Kingdom (UK). Using Scotland as a strategically bounded case study, it examines persistent knowledge gaps among women and primary care professionals and their implications for equitable menopause care.

KEY ISSUES: Menopause involves significant neuroendocrine changes that affect brain metabolism, structure, and cognition, contributing to women's disproportionate Alzheimer's disease risk. Although hormone replacement therapy may alleviate neurological and cognitive symptoms - and may offer neuroprotective benefits when initiated early - clinical uncertainty, stigma, and inconsistent guidance continue to delay recognition, support, and treatment. These gaps translate into avoidable cognitive decline, reduced quality of life, and marked inequities in access to menopause care.

IMPLICATIONS: Targeted primary care training, coherent public communication, and UK-specific investment in evidence-based menopause services are urgently required. This programme of research is situated within Scotland as a strategically bounded, devolved health system, allowing for a focused examination of how brain health is addressed within menopause policy and practice. By embedding brain health within Scotland's Women's Health Plan, the findings will inform future comparative and UK-wide research and contribute to the development of equitable, person-centred, and brain-health informed menopause care across the lifespan.},
}

Humans
Female
Scotland
*Menopause/physiology/psychology
Women's Health
*Health Policy
*Brain/physiology
*Hormone Replacement Therapy
Health Knowledge, Attitudes, Practice
Alzheimer Disease/prevention & control
Primary Health Care
Quality of Life

@article {pmid42484463,
year = {2026},
author = {Chen, Y and Kwapong, WR and Chen, X and Gao, Y and Chu, M and Zhang, X and Wu, L},
title = {Retinal structural and microvascular alterations as biomarkers of cerebral pathology and cognitive decline in Alzheimer's disease: An OCT/OCTA study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470439},
doi = {10.1177/13872877261470439},
pmid = {42484463},
issn = {1875-8908},
abstract = {BackgroundRetinal structural and microvascular alterations detected by optical coherence tomography (OCT) and OCT angiography (OCTA) have emerged as promising biomarkers of Alzheimer's disease (AD). However, the extent to which retinal changes reflect cerebral neurodegenerative and vascular pathology and contribute to cognitive impairment remains incompletely characterized.ObjectiveTo investigate the relationships among retinal OCT/OCTA metrics, cerebral neuroimaging markers, and global cognitive performance in patients with AD.Methods115 AD and 101 cognitively unimpaired controls underwent OCT/OCTA imaging, 3.0T brain magnetic resonance imaging, and neuropsychological assessment. Retinal structural measures, including peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses, and retinal microvascular densities of the superficial vascular complex (SVC) and deep vascular complex were analyzed alongside white matter hyperintensity (WMH) volume, hippocampal volume, and cerebral small vessel disease (SVD) burden.ResultsCompared with controls, patients with AD exhibited significantly thinner pRNFL and GCIPL and lower SVC density (all p < 0.01). Retinal structural and microvascular alterations were associated with greater WMH burden, hippocampal atrophy, increased SVD burden, and lower Mini-Mental State Examination and Montreal Cognitive Assessment scores (all p < 0.05). Significant interactions were observed between GCIPL thickness and periventricular WMH volume in relation to cognitive performance. Mediation analyses demonstrated that WMH volume and SVD burden partially mediated the association between reduced SVC density and cognitive impairment.ConclusionsRetinal OCT/OCTA metrics are associated with cerebral neurodegenerative and vascular abnormalities and reflect cognitive dysfunction in AD, supporting their potential utility as accessible, noninvasive biomarkers for disease assessment and monitoring.},
}

@article {pmid42484467,
year = {2026},
author = {Ramos-Henderson, M and Aliaga-Gallardo, P and Aguilar-Riveros, C and Fuentes, L and Calderón, C and Domic-Siede, M},
title = {Associations between higher-order executive planning and subjective cognitive decline in middle-aged individuals.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470712},
doi = {10.1177/13872877261470712},
pmid = {42484467},
issn = {1875-8908},
abstract = {BackgroundSubjective cognitive decline (SCD) is a recognized risk factor for future objective cognitive impairment and dementia. Although widely studied in older adults, SCD during midlife remains underexplored, despite this period representing a critical window for early detection. Higher-order executive functions, particularly cognitive planning, may be especially sensitive to subtle cognitive changes at this stage.ObjectiveTo examine the association between higher-order executive function performance and subjective cognitive decline in middle-aged individuals.MethodsThis cross-sectional study included 167 community-dwelling middle-aged adults (45-60 years) with SCD and normal global cognition. Participants completed the Subjective Cognitive Decline Questionnaire (SCDq), mood and sleepiness measures, structured executive function tests, and the Zoo Map Test (ZMT) to assess higher-order executive planning. Group comparisons, correlation analyses, and hierarchical linear regressions were performed.ResultsHigher SCD levels were associated with longer planning times and more planning errors on the ZMT. No associations were observed between SCD and global cognitive performance or structured executive function measures. In the hierarchical regression model, mood symptoms and daytime sleepiness explained 23% of SCD variance, while higher-order executive planning measures accounted for an additional 8.4%, yielding a final hierarchical model explaining 33.6% of the variance. Fully adjusted simultaneous model showed the same pattern.ConclusionsSCD in midlife is associated with subtle differences in higher-order executive functioning that emerge under high cognitive demand. Ecologically valid executive tasks may improve early detection of individuals at risk for future objective cognitive decline beyond traditional neuropsychological measures.},
}

@article {pmid42484558,
year = {2026},
author = {Arnold, MR and Westaway, SK and Woltjer, RL and Gray, NE and Quinn, JF},
title = {E326K GBA polymorphism is associated with clinical and pathological features of synucleinopathy in the absence of overt Parkinson's disease or Lewy body dementia.},
journal = {Journal of Parkinson's disease},
volume = {},
number = {},
pages = {1877718X261468542},
doi = {10.1177/1877718X261468542},
pmid = {42484558},
issn = {1877-718X},
abstract = {Heterozygote carriers of Gaucher's disease mutations and other polymorphisms in the glucocerebrosidase (GBA) gene show an increased incidence of Parkinson's disease. We hypothesized that common GBA polymorphisms would be associated with subtle parkinsonian features, mild cognitive impairment, and "silent" Lewy body (LB) pathology in aging individuals without a clinical diagnosis of parkinsonism. The most prevalent GBA variants, T369M and E326K, appear in the general population at rates of approximately 0.6% and 1%, respectively. We evaluated 845 participants from the Oregon Alzheimer's Disease Research Center (OADRC) with SNP data generated by the National Centralized Repository of Alzheimer's Disease (NCRAD). Twenty-one subjects were E326K carriers and eighteen were T369M carriers. Clinical measures and postmortem neuropathology were compared between each SNP group and non-carriers. Although there were no statistically significant clinical differences related to synucleinopathy across groups, neuropathological analyses revealed a significantly higher prevalence of LB pathology in E326K carriers compared to T369M carriers. When stratifying each genetic group by LB status (LB+ or LB-), LB+ E326K carriers demonstrated a significant reduction in Mini-Mental State Examination (MMSE) scores compared with LB- non-carriers and a modest decrease compared with T369M carriers. These preliminary findings from a small, uni-center cohort suggest that the E326K GBA polymorphism may predict LB pathology and subtle cognitive decline in aging individuals who lack overt parkinsonian symptoms. Further validation in a larger cohort is warranted. Identifying at-risk individuals through targeted genetic screening may ultimately support earlier intervention and preventative care strategies.},
}

@article {pmid42484559,
year = {2026},
author = {Ashar, MS and Anwar, M and Singh, AK and Pradhan, R and Gupta, A and Chakrawarty, A and Haldar, P and Tripathi, M and Dey, S},
title = {Quantitative correlation between extracellular matrix protein degradation and the progression of neurodegeneration in Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470815},
doi = {10.1177/13872877261470815},
pmid = {42484559},
issn = {1875-8908},
abstract = {BackgroundThe extracellular matrix (ECM) supports synaptic connections. Breakdown of ECM net component perineuronal nets (PNN) loses synaptic plasticity and causes the symptoms of neurological disorder like Alzheimer's diseases (AD).ObjectiveThis study analyzed PNN proteins and Tenascin-C (TNC), in the blood of AD, mild cognitive impairment (MCI) patients, and geriatric controls (GC), with correlation with tau and p-tau levels.MethodsThis case control study included 77 AD, 53 MCI patients, and 51 GC. Serum PNN and TNC levels were measured by surface plasmon resonance (SPR) method and validated by western blot. Statistical analyses included Kruskal-Wallis, logistic regression, Spearman correlation and receiver operating curve.ResultsPNN proteins and TNC were significantly elevated in AD compared to MCI and GC. Aggrecan and versican showed strong discriminatory power for AD from MCI, while TNC distinguished MCI from GC, indicating its potential for early detection of cognitive decline. Higher protein levels correlated with lower cognitive scores. Western blot result was consistent with SPR findings.ConclusionsThese results emphasize the significance of ECM proteins as biomarkers for cognitive impairments, showcasing their diverse diagnostic capabilities for AD. These findings provide further support for the involvement of PNN proteins in the pathophysiology of AD during early stage.},
}

@article {pmid42484690,
year = {2026},
author = {Yao, Q and Han, X and Cui, T and Li, D and Shan, A and Wang, X and Li, S and Luan, H and Zhu, Y and Wen, B and Sun, Y and Li, C and Sun, Q and Wei, C},
title = {Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42484690},
issn = {1432-1459},
support = {2021ZD0201802//Innovation of Science and Technology 2030 - Major Project on Brain Science and Brain-Inspired Intelligence Research/ ; 82471450//National Nature Science Foundation of China/ ; XCSTS-SD2024-02//Xicheng District Science and Technology Special Project/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/physiopathology/therapy ; Animals ; *Brain/metabolism/physiopathology ; *Glymphatic System/metabolism/physiopathology ; *Choroid Plexus/metabolism/physiopathology ; Amyloid beta-Peptides/metabolism ; Meninges/metabolism ; *Cerebrospinal Fluid/metabolism ; },
abstract = {Alzheimer's disease (AD) is usually regarded as a neurodegenerative disorder defined by amyloid-β (Aβ) deposition and abnormal tau accumulation. Increasing evidence suggests that reduced clearance of metabolic waste and pathological proteins from the brain also contributes to disease onset and progression. Previous studies have often considered choroid plexus (CP) function, glymphatic exchange, and meningeal lymphatic drainage as separate clearance processes. A continuous framework linking these structures and functions is still lacking. This review integrates recent clinical and experimental evidence and proposes the brain clearance continuum as an interpretative framework. It describes three interlinked functional interfaces: the upstream choroid plexus-cerebrospinal fluid (CP-CSF) inflow interface, the midstream parenchymal perivascular exchange interface, and the downstream meningeal lymphatic outflow interface. Under physiological conditions, these interfaces support CSF movement, parenchymal solute exchange, and the outward removal of metabolic waste. In AD, disrupted CSF homeostasis, impaired perivascular exchange, and obstructed meningeal lymphatic outflow may interact, leading to serial failure of the brain clearance continuum. This process is closely associated with Aβ/tau accumulation, vascular dysfunction, neuroinflammation, and cognitive decline. We also summarise potential therapeutic strategies directed at different clearance interfaces, whilst emphasising that most evidence remains preclinical or exploratory. The brain clearance continuum provides a systematic framework for understanding clearance failure in AD. It may also offer a theoretical basis for future mechanistic studies and therapeutic development that are stratified by clearance interface and disease stage.},
}

Humans
*Alzheimer Disease/metabolism/physiopathology/therapy
Animals
*Brain/metabolism/physiopathology
*Glymphatic System/metabolism/physiopathology
*Choroid Plexus/metabolism/physiopathology
Amyloid beta-Peptides/metabolism
Meninges/metabolism
*Cerebrospinal Fluid/metabolism

@article {pmid42484748,
year = {2026},
author = {Abroumand Gholami, A and Ghadiminia, N and Akhrorova, S and Kubaev, A and Agamurodov, S and Salomova, F},
title = {Correspondence: Erythrina caffra in cadmium-induced Alzheimer's-like pathology: A new candidate or a familiar pattern?.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42484748},
issn = {1573-4978},
mesh = {*Alzheimer Disease/drug therapy/chemically induced/pathology/metabolism ; Animals ; *Cadmium/toxicity ; *Plant Extracts/pharmacology/therapeutic use ; *Erythrina/chemistry/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; Humans ; Rats ; Oxidative Stress/drug effects ; Disease Models, Animal ; },
abstract = {Cadmium neurotoxicity has been increasingly linked to neurodegenerative processes, and plant-derived compounds are being explored for their protective potential. The recent study by Ed-Day and colleagues investigated the neuroprotective effects of Erythrina caffra seed extract in a cadmium-induced Alzheimer's-like model in rats, reporting improvements in memory, cholinergic function, oxidative stress, and neuroinflammation. Four principal concerns are identified: (1) treatment protocol ambiguity, use of young rats to model an age-related disease, and unclear prevention-versus-therapy distinction; (2) memantine as positive control, mechanistically mismatched with cadmium toxicity pathways; (3) claim of Alzheimer's-like pathology without measuring Aβ plaques and tau tangles; and (4) no cadmium quantification in tissues or biofluids, leaving the mechanism, direct neuroprotection versus reduced bioavailability, unresolved. While the study offers promising preliminary evidence for the neuroprotective potential of E. caffra, its translational significance is constrained by these methodological and interpretative limitations. Addressing these concerns in future investigations would strengthen the evidence base for this medicinal plant's therapeutic potential.},
}

*Alzheimer Disease/drug therapy/chemically induced/pathology/metabolism
Animals
*Cadmium/toxicity
*Plant Extracts/pharmacology/therapeutic use
*Erythrina/chemistry/metabolism
*Neuroprotective Agents/pharmacology/therapeutic use
Humans
Rats
Oxidative Stress/drug effects
Disease Models, Animal

@article {pmid42484778,
year = {2026},
author = {Lill, CM and Homann, J and Ohlei, O and Smith-Byrne, K and Viallon, V and Huerta, JM and Artaud, F and Zhao, Y and Britten, A and Deecke, L and Dobricic, V and Mokoroa, O and Guevara, M and Petrova, D and Trupp, M and Sabin, J and Gröninger, M and Colorado-Yohar, SM and Alonso-Martin, S and Cabrera-Castro, N and Groppa, S and Robinson, O and Hansen, J and Eriksson, S and Sieri, S and Jimenez, A and Tong, TYN and Kaaks, R and Severi, G and Travis, R and Wareham, N and Benedet, AL and Zetterberg, H and Franke, A and Elbaz, A and Bertram, L and Vermeulen, R and Middleton, L and Masala, G and Sacerdote, C and Peters, S and Katzke, V and Ferrari, P and Gunter, MJ and Riboli, E},
title = {EPIC4ND-European Prospective Investigation into Cancer and Nutrition follow-up for neurodegenerative diseases.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {42484778},
issn = {1573-7284},
support = {#008994//Michael J Fox Foundation/ ; JPND2021-650-289//EU Joint Programme - Neurodegenerative Disease Research/ ; LI 2654/3-1//Deutsche Forschungsgemeinschaft/ ; LI 2654/4-1 (Heisenberg)//Deutsche Forschungsgemeinschaft/ ; INTRAIBS-2020-06//Instituto de Investigación Biosanitaria ibs.GRANADA/ ; },
abstract = {The 'European Prospective Investigation into Cancer and Nutrition' cohort (EPIC) is a prospective study including ~ 520,000 participants recruited across Europe (1991-2000) with in-depth baseline data on nutritional, lifestyle, medical, and anthropometric variables, and baseline blood samples. Here we introduce EPIC4ND, a case-cohort study within EPIC designed to identify biomarkers predicting a future onset of dementia, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). EPIC4ND comprises 6415 initially non-diseased participants (aged 35-80 years, mean age at baseline: 54 ± 9, 64% women) including 1899 incident cases with up to 30 years of follow-up and data on at least one omics domain available from pre-disease blood samples. EPIC4ND includes 4604 subcohort members (4441 non-cases and 163 incident cases) and 1811 additional incident cases ascertained from the broader EPIC cohort. Among the incident cases, there are 1190 dementia cases (818 AD), 610 PD cases, and 199 ALS cases. Additionally, 72 prevalent PD cases and 118 incident Parkinsonism cases are available for comparison. Molecular data generated encompass proteomics, genome-wide DNA methylation, and SNP genotyping with 4127 EPIC4ND participants (including 1635 incident cases) having data on all three domains. Smaller studies include data on metals, metabolites, and environmental chemicals, while ongoing efforts focus on ultrasensitive targeted biomarker measurements and small RNA sequencing. Genome-wide association studies and analyses of epidemiological risk factors validate the dataset by confirming many known risk factors. Leveraging these extensive pre-disease multi-layered omics data offers a unique opportunity to identify biomarker signatures predicting neurodegenerative diseases and to explore their interplay with epidemiological risk factors.},
}

@article {pmid42484938,
year = {2026},
author = {Wu, P and Liao, Y and Liu, C and Liu, X and Feng, Q and Cheng, X},
title = {The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42484938},
issn = {1559-1182},
mesh = {Humans ; *Alzheimer Disease/therapy/pathology/metabolism/physiopathology/immunology ; *Glymphatic System/pathology/metabolism ; Animals ; Amyloid beta-Peptides/metabolism ; *Lymphatic System ; },
abstract = {While anti-amyloid-beta (Aβ) monoclonal antibodies have achieved substantial success in reducing plaque burden, their modest clinical impact highlights an "efficacy ceiling" that necessitates a re-evaluation of Alzheimer's disease (AD) pathogenesis. This review proposes a shift from an amyloid-centered paradigm to a "clearance-centered bottleneck" framework, conceptualizing brain homeostasis as a coupled glymphatic-lymphatic circuit. We identify three critical rate-limiting nodes-entry, transit, and exit-that govern this circuit. These nodes fail through distinct mechanisms: arterial stiffening (entry), aquaporin-4 (AQP4) depolarization (transit), and cerebral amyloid angiopathy with impaired meningeal lymphatic drainage (exit). This multilevel failure creates a self-sustaining "neuroimmune stalemate"-a state in which trapped antigens and inflammatory mediators perpetuate glial reactivity that further degrades the very clearance infrastructure needed to resolve it. Distinct from prior reviews of glymphatic dysfunction in isolation, this review contributes four interlinked advances: an integrated glymphatic-lymphatic coupled-circuit framework; a bidirectional immune-clearance crosstalk model; a critical appraisal of imaging endpoints graded by trial-readiness; and a combination therapy roadmap. To overcome the current therapeutic plateau, we advocate for multinode interventions that combine amyloid-targeting therapies with clearance-enhancing agents, supported by a readiness-tiered imaging strategy-standardized proxies such as DTI-ALPS and PVS burden as enrichment/secondary endpoints and dynamic contrast-enhanced MRI for mechanistic proof-of-concept.},
}

Humans
*Alzheimer Disease/therapy/pathology/metabolism/physiopathology/immunology
*Glymphatic System/pathology/metabolism
Animals
Amyloid beta-Peptides/metabolism
*Lymphatic System

@article {pmid42484959,
year = {2026},
author = {Lin, Q and Qiu, N and Wang, X and Wei, YB and Liu, JJ},
title = {Chronic Pain and the Risk of Dementia: A Systematic Review and Meta-Analysis.},
journal = {Current pain and headache reports},
volume = {30},
number = {1},
pages = {},
pmid = {42484959},
issn = {1534-3081},
mesh = {Humans ; *Dementia/epidemiology/etiology ; *Chronic Pain/epidemiology/complications ; Risk Factors ; },
abstract = {BACKGROUND: The relationship between chronic pain and dementia risk has been extensively studied, but findings remain inconclusive. We conducted an updated meta-analysis to synthesize evidence from recent large-scale cohort studies.

METHODS: Two authors independently and systematically searched PubMed, Web of Science, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure for cohort studies published through April 2025, with a minimum follow-up of one year. Hazard ratios (HRs) were considered equivalent to risk ratios (RRs) assuming low event rates. Random-effect models pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup analyses and meta-regression explored heterogeneity.

RESULTS: Of 3,823 publications, 30 studies met the inclusion criteria. After excluding five studies with overlapping populations, 25 studies involving 2,091,835 participants were pooled in the primary analysis. Individuals with chronic pain had a 28% higher dementia risk (RR = 1.28, 95% CI = 1.18-1.38). Heterogeneity was high (I²=91%). Subgroup analyses showed migraine, headaches, arthritis-related pain, and widespread pain were associated with increased risk. The association was significant in Asia but not in America or Europe, and when using ICD (but not DSM) criteria. Chronic pain increased the risk of Alzheimer's disease and non-vascular dementia, but not vascular dementia. Study quality, region, measurement methods, and pain types influenced the relationship. Pain type was a source of heterogeneity.

CONCLUSIONS: In this meta-analysis of cohort studies, chronic pain was associated with an increased risk of dementia. Due to the observational nature of the included studies and high heterogeneity, this association should not be interpreted as causal. Further research is needed to determine whether pain management can mitigate dementia risk.},
}

Humans
*Dementia/epidemiology/etiology
*Chronic Pain/epidemiology/complications
Risk Factors

@article {pmid42485421,
year = {2026},
author = {Yang, S and Cui, L and Zhang, J and Yang, Y and Huo, J and Ding, Y and Zhang, J and He, S and Li, J},
title = {Association of triglyceride-glucose index (TyG) and a body shape index (ABSI) with cognitive decline and dementia risk.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0354418},
doi = {10.1371/journal.pone.0354418},
pmid = {42485421},
issn = {1932-6203},
mesh = {Humans ; *Triglycerides/blood ; *Dementia/blood/epidemiology ; *Cognitive Dysfunction/blood/epidemiology ; Female ; Male ; *Blood Glucose/analysis/metabolism ; Aged ; Risk Factors ; },
abstract = {BACKGROUND: Longitudinal evidence linking the body shape index (ABSI) to dementia and its subtypes remains scarce. Furthermore, the use of ABSI and TyG-ABSI as predictors of cognitive decline and dementia is infrequent. Therefore, this study aimed to examine the relationships between the triglyceride-glucose (TyG) index, ABSI, and TyG-ABSI indices and their predictive value for cognitive decline and dementia risk.

METHODS: This study included 370,744 participants from the UK Biobank. The TyG and ABSI indices were calculated using their respective formulas, while the TyG-ABSI index was derived by multiplying TyG and ABSI. Cognitive decline was defined as scoring in the bottom 25% on cognitive tests, while dementia was diagnosed from first-recorded incidents and algorithmically-defined outcomes. Logistic regressions were employed to assess the associations of TyG, ABSI and TyG-ABSI indices with cognitive decline; Cox regressions were used to analyze the associations of these indices with the risk of all-cause dementia (ACD) and its subtypes.

RESULT: The TyG, ABSI, and TyG-ABSI indices were all significantly associated with cognitive decline. Additionally, compared with the lowest quartiles, the highest quartiles of TyG, ABSI and TyG-ABSI indices were associated with a significantly increased risk of ACD by 33% (HR = 1.33, 95% CI: 1.13-1.57), 79% (HR = 1.79, 95% CI: 1.65-1.94) and 67% (HR = 1.67, 95% CI: 1.54-1.82), respectively. These indices were also significantly associated with the risk of Alzheimer's disease (AD) and vascular dementia (VD) (all P < 0.05).

CONCLUSION: The TyG, ABSI, and TyG-ABSI indices are significantly and positively linked to the risk of cognitive decline and dementia.},
}

Humans
*Triglycerides/blood
*Dementia/blood/epidemiology
*Cognitive Dysfunction/blood/epidemiology
Female
Male
*Blood Glucose/analysis/metabolism
Aged
Risk Factors

@article {pmid42485548,
year = {2026},
author = {Moradi Sarcheshmeh, MS and Shahedi, A and Zabihirad, J and Taghipour, M and Kargar Jahromi, H and Delam, H},
title = {Global Prevalence of Urinary Incontinence in Individuals With Dementia: A Systematic Review and Meta-Analysis.},
journal = {Neurourology and urodynamics},
volume = {},
number = {},
pages = {},
doi = {10.1002/nau.70390},
pmid = {42485548},
issn = {1520-6777},
abstract = {BACKGROUND: Urinary incontinence (UI) is a common and debilitating complication in patients with dementia, significantly impacting quality of life, increasing caregiver burden, and accelerating institutionalization.

OBJECTIVE: Despite numerous studies, reported prevalence estimates vary widely, and a precise global pooled prevalence has not been established.

METHODS: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from November to December 2025, without publication year restrictions. Observational studies reporting the point prevalence of UI in dementia patients were included. Two independent reviewers screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale. A random-effects meta-analysis (restricted maximum likelihood method) was used to pool prevalence estimates. Heterogeneity was assessed using the I[2] statistic. Subgroup analyses were performed by setting and UI assessment method, and meta-regression examined associations with Human Development Index (HDI) and temporal trends.

RESULTS: Ten studies comprising 286,544 participants were included. The pooled global prevalence of UI in dementia patients was 39.7% (95% CI: 23.9%-58.1%), with substantial heterogeneity (I[2] > 95%). Prevalence ranged from 4% in Taiwan to 88% in Japan. Subgroup analyses revealed significantly higher prevalence in clinic/hospital settings compared to community settings (47.5% vs. 28.7%, p = 0.023), and in studies using single-question interviews versus medical record extraction (59.2% vs. 23.2%, p = 0.016). Meta-regression showed a significant positive association with HDI (coefficient: 5.69, p < 0.001). Sensitivity analysis confirmed the robustness of the pooled estimate.

CONCLUSION: Approximately 40% of dementia patients experience UI, with substantial variation by setting and assessment method. Standardized assessment protocols are needed to inform targeted interventions and reduce disease burden.},
}

@article {pmid42485607,
year = {2026},
author = {Chen, Y and Chen, A and Power, MC and Grodstein, F and Kapasi, A and Capuano, AW and Lange-Maia, BS and Moghtaderi, A and Stapp, EK and Bhattacharyya, J and Shah, RC and Barnes, LL and Bennett, DA and James, BD},
title = {Associations of Alzheimer Disease and Related Dementia Neuropathologies With Timely Diagnosis of Dementia in Healthcare Settings.},
journal = {Neurology},
volume = {107},
number = {3},
pages = {e218352},
doi = {10.1212/WNL.0000000000218352},
pmid = {42485607},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; *Alzheimer Disease/pathology/diagnosis ; Aged, 80 and over ; Retrospective Studies ; *Dementia/diagnosis/pathology ; Aged ; *Brain/pathology ; United States ; Cohort Studies ; Medicare ; },
abstract = {BACKGROUND AND OBJECTIVES: A timely diagnosis of dementia may provide valuable time for treatment and planning, yet underdiagnosis is common. This study investigated the relationship between presence of dementia pathologies and timeliness of dementia diagnosis by healthcare providers.

METHODS: This was a retrospective study using 5 cohorts at Rush Alzheimer's Disease Center. We included participants who met all of the following criteria: (1) incident dementia based on annual cohort assessments, (2) linkage to Medicare records, and (3) a completed postmortem brain autopsy. Postmortem neuropathologic examinations identified the presence of AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), vascular pathologies, and neocortical Lewy bodies (LBs). In linked Medicare data, we defined timely diagnosis as the presence of claims with dementia diagnoses within 3 years before or 1 year after the cohort-based dementia onset. We used logistic regressions to quantify associations of neuropathology markers with timely diagnosis vs underdiagnosis.

RESULTS: Of the 500 eligible participants (71% female, 95% non-Latino White, mean [SD] age at cohort dementia onset = 88 [7] years, mean [SD] years from onset to death = 4 [3]), only 54% received a timely diagnosis. After controlling for demographics, time to death, and other neuropathologies, a pathologic diagnosis of AD (OR = 1.91, 95% CI 1.21-3.00) and moderate/severe LATE-NC pathologies (OR = 1.83, 95% CI 1.25-2.68) were independently associated with higher odds of timely diagnosis. Moderate/severe vascular pathologies (OR = 0.94, 95% CI 0.55-1.59) and neocortical LB pathologies (OR = 1.00, 95% CI 0.64-1.55) were not significantly associated with receipt of a timely diagnosis. In a separate multivariable logistic regression, we found that participants with 3 or 4 neuropathologies present had an over 2-fold increase in odds of timely diagnosis (OR = 2.24, 95% CI 1.32-3.82), compared with those with 1 or no neuropathology.

DISCUSSION: In deceased older adults with cohort-determined incident dementia, the healthcare system was twice as likely to capture those with pathologic diagnosis of AD, moderate/severe LATE-NC, and more than 3 copathologies in a timely manner. While findings from this predominantly White and highly educated sample warrant replication in broader population, this study is an important initial step toward understanding biological correlates of timely diagnosis of dementia.},
}

Humans
Female
Male
*Alzheimer Disease/pathology/diagnosis
Aged, 80 and over
Retrospective Studies
*Dementia/diagnosis/pathology
Aged
*Brain/pathology
United States
Cohort Studies
Medicare

@article {pmid42485616,
year = {2026},
author = {Silva, JAFD and Nagra, A and Wadhwa, A and Mar, S and Tjoa, A and Flibotte, S and Barvalia, M and Matos, I and Priatel, J and Krebs, D and Harder, KW},
title = {A DLL1-culture system to propagate murine patrolling monocytes from bone marrow progenitors.},
journal = {Journal of leukocyte biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jleuko/qiag103},
pmid = {42485616},
issn = {1938-3673},
abstract = {Patrolling monocytes (pMos) scavenge debris from vessel walls and mediate antibody-dependent cellular phagocytosis, making them attractive cell therapy candidates for cancer, atherosclerosis, and Alzheimer's disease. However, methods to generate enhanced numbers of pMos are not available. To address this, we developed a two-step procedure to produce pMos in vitro from murine bone-marrow (BM). First, myeloid progenitors were expanded and enriched from BM using cytokines for four days. Second, expanded progenitors were differentiated into pMos on DLL1-expressing monolayers for eight days. We confirmed that in vitro grown pMos expressed the transcription factor Nr4a1 (Nur77) and other canonical pMos surface proteins, and depended on Notch signalling for their development. RNA sequencing revealed that in vitro pMos expressed hallmark pMos genes, including Cx3cr1, Itgax (CD11c), CD43, Fcγr4, and Cd274 (PD-L1), and their gene signatures clustered closely with in vivo blood and BM pMos. Transcriptomic and phenotypic analyses further demonstrated that in vitro pMos were distinct from classical BM macrophages. Phagocytosis assays demonstrated the function of in vitro pMos in cancer cell uptake. Adoptive transfer studies demonstrated that in vitro pMos persisted within the circulation and lung vasculature during the early post-transfer period compared with BM-derived macrophages, consistent with the vascular-patrolling properties of pMos. Adoptive transfer of pMos reduced lung tumour burden in a metastatic model, supporting an anti-tumoural role for pMos and their ability to mediate immune surveillance in vivo. These findings demonstrate that the DLL1 culture system allows for propagation of functional pMos, enabling studies of pMos biology and their therapeutic potential.},
}

@article {pmid42485924,
year = {2026},
author = {Xing, Z and Liu, Z and Zhang, DF and Xie, K and Fang, J and Bi, XA and Liu, T},
title = {Alzheimer's disease risk prediction via perceptual deformable attention generative adversarial network with large foundation models.},
journal = {Medical image analysis},
volume = {113},
number = {},
pages = {104225},
doi = {10.1016/j.media.2026.104225},
pmid = {42485924},
issn = {1361-8423},
abstract = {Predicting the risk of Alzheimer's disease (AD) is fundamental for early-stage intervention. Nevertheless, most methods struggle to extract multi-omics associative patterns due to the limited feature perception and inflexible disease modeling. This paper proposes a novel evolutionary pattern mining framework for precise disease risk prediction. Firstly, large foundational models are employed to automatically construct high-quality features. Second, a perceptual deformable attention mathematical model is proposed, which combines multi-scale sparse attention and deformable attention mechanisms to capture evolutionary patterns of fused multi-omics features. Finally, a Perceptual Deformable Attention Generative Adversarial Network (PDAT-GAN) is developed. PDAT-GAN can precisely simulate the evolutionary procedure of AD using multi-omics data, thereby achieving robust risk prediction and pathogeny extraction for AD. We validate the advanced performance and interpretability of PDAT-GAN on public datasets, underscoring significance of PDAT-GAN in supporting clinical intervention and pathogenetic research. The code of PDAT-GAN can be accessed at: .},
}

@article {pmid42486010,
year = {2026},
author = {Li, X and Li, S and Su, J and Zheng, F and Li, S and Zhao, X and Chen, D and Yan, J and Xia, C},
title = {Merocyanine derivatives as theranostic agents for cognitive improvement and real-time imaging of amyloid-β in APP/PS1 transgenic mice.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {363},
number = {Pt 1},
pages = {128458},
doi = {10.1016/j.saa.2026.128458},
pmid = {42486010},
issn = {1873-3557},
abstract = {Amyloid-β (Aβ) is widely recognized as a biomarker for the diagnosis and treatment of Alzheimer's Disease (AD). In our previous work, a series of merocyanine fluorescent probes were designed, synthesized and evaluated for the imaging of Aβ plaques. Here, we further identified the representative probe D4, which not only demonstrates the characteristics of a highly sensitive fluorescent probe for real-time imaging of Aβ content in the brain of APP/PS1 mice, but also exhibited the ability to treat AD, including inhibition of Aβ aggregation (inhibition rate: 89.5%), antioxidant activity (3.4 times that of Trolox); AChE inhibitory activity (IC50 = 0.5 ± 0.0 μM) and the capacity to cross the BBB (Pe = 8.6 ± 0.7). Additionally, D4 dramatically attenuates Aβ-induced SH-SY5Y cell death by preventing the generation of ROS, and intravenous administration of 0.5 mg/kg D4 for 15 days significantly improved the cognitive ability of 7-month-old APP/PS1 mice by protecting hippocampal and cortex neurons from necrosis, attenuating oxidative stress in the hippocampus and cortex, and reducing Aβ burden deposition. These findings strongly suggest that D4 owns a high theranostic potential for treating AD.},
}

@article {pmid42486312,
year = {2026},
author = {Jafar, T and Chowdhury, NF and Irimia, A},
title = {Spatial Transcriptomic Decoupling and Magnetic Resonance Imaging Identify the Genetic and Cytoarchitectonic Correlates of Regional Vulnerability in Alzheimer's Disease.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {122144},
doi = {10.1016/j.neuroimage.2026.122144},
pmid = {42486312},
issn = {1095-9572},
abstract = {The genetic and cytoarchitectonic factors associated with neurodegeneration in Alzheimer's disease (AD) remain poorly understood due to challenges linking gene expression to macroscale neuroanatomic features. Gray-white matter contrast C, an MRI-derived measure sensitive to relative cortical tissue contrast and myelin-related lipid content, declines with aging and AD. By relating C to spatial transcriptomics, we identify AD-related alterations in gene-C coupling. Spatial gene expressions facilitate comparing C between cognitively normal adults (CN, N = 1,447) and adults with AD (N = 1,447) from the National Alzheimer's Coordinating Center (NACC, N = 2,286) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 608). For 25 genes, expression significantly correlates with mean C in AD, but not CN, participants. Cell-type enrichment links AD-correlated genes to astrocytic, endothelial, neuronal markers, in cortical regions with age-related C decline. NACC findings are reproduced in ADNI. Amyloid and tau PET corroborate that regions with AD-related alterations in gene-C coupling also exhibit molecular AD signatures. This multimodal convergence supports spatial transcriptomic associations with cytoarchitectonic changes and AD pathology. We integrate transcriptomics with neuroimaging to identify how genes involved in AD are associated with cortical lipid content, providing novel insights into the genetics of neurodegeneration.},
}

@article {pmid42486320,
year = {2026},
author = {Dilip, PI and Daksh, R and Sharma, P and Khanna, S and Bojja, SL and Singh, AK and Nampoothiri, M},
title = {Repressor Element 1 Silencing Transcription Factor as a central regulator of autophagy and neuroinflammation in Alzheimer's disease.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179168},
doi = {10.1016/j.ejphar.2026.179168},
pmid = {42486320},
issn = {1879-0712},
abstract = {Repressor element-1 silencing transcription factor (REST) is a critical epigenetic regulator involved in multiple cellular processes, including apoptosis, autophagy, and neuronal survival. By modulating the expression of neuronal and stress-response genes, REST contributes significantly to neuroprotection. REST is predominantly localised in the nucleus; however, in Alzheimer's Disease (AD), nuclear REST is reduced, leading to transcriptional dysregulation and contributing to AD pathology. The low levels of REST are associated with defective autophagy flux, including mitochondrial dysfunction and enhanced vulnerability to toxic protein aggregates, causing AD and other neurodegenerative disorders. Recent research shows that REST suppresses several apoptotic genes, modulating neuroinflammatory signalling and regulates autophagy. The specific regulatory mechanism of REST suggests new strategies for the prevention and treatment of AD and ageing. Despite REST's unique functions and importance in AD, its precise role and the molecular mechanisms underlying REST-mediated signalling pathways have not been comprehensively reviewed. The purpose of this review is to provide an overview of the structural and functional characteristics of REST, explore the mechanisms underlying REST-mediated autophagy, neuroinflammation and apoptosis in AD and discuss the emerging therapeutic implications of targeting REST.},
}

@article {pmid42486330,
year = {2026},
author = {Arriagada, J and Ardiles, Á and Mery, E and Garay, C and Conejera, F and Herrera, EA and Paula-Lima, A and Muñoz, P},
title = {Metformin enhances hippocampal excitatory synaptic transmission and preserves synaptic plasticity under amyloid-β oligomer-induced dysfunction.},
journal = {Neuropharmacology},
volume = {299},
number = {},
pages = {111116},
doi = {10.1016/j.neuropharm.2026.111116},
pmid = {42486330},
issn = {1873-7064},
abstract = {Early stages of Alzheimer's disease (AD) are characterized by synaptic dysfunction and alterations in synaptic plasticity that precede neuronal loss. Soluble amyloid-β oligomers (AβOs) are important contributors to these early synaptic alterations by disrupting excitatory neurotransmission and impairing hippocampal function. Metformin (Met), a widely used antidiabetic drug, has recently gained attention for its potential neuroprotective properties; however, its effects on hippocampal synaptic transmission and plasticity under amyloid-induced stress remain incompletely understood. In the present study, we investigated the effects of orally administered Met (200 mg/kg/day) on basal excitatory synaptic transmission, presynaptic release probability, and long-term synaptic plasticity in hippocampal slices from rats subjected to stereotaxic injection of AβOs into the CA1 region. Using field electrophysiological recordings, we show that Met significantly enhances basal excitatory synaptic transmission, increases presynaptic release probability, potentiates long-term potentiation (LTP), and attenuates long-term depression (LTD). Notably, Met prevented the impairments in synaptic transmission and plasticity induced by AβOs, maintaining synaptic responses at levels comparable to those observed in control animals. Together, these findings indicate that Met modulates hippocampal synaptic function and preserves physiological forms of synaptic plasticity under amyloid-induced stress conditions. Our results identify synaptic transmission and plasticity as functionally relevant targets of Met action and support further investigation of Met as a potential strategy for preserving synaptic function during the early stages of AD.},
}

@article {pmid42486339,
year = {2026},
author = {Yin, N and Ding, H and Su, R and Chen, Y and Zhou, L and Tao, Y and Chen, H and Sun, Z and Li, J},
title = {Multimodal Characterization of Age-Dependent Susceptibility to High-Cholesterol-Diet-Induced AD-like Alterations in WHBE Rabbits.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106229},
doi = {10.1016/j.neuint.2026.106229},
pmid = {42486339},
issn = {1872-9754},
abstract = {Rabbit models induced by a high-cholesterol diet can exhibit Alzheimer's disease (AD)-like neuropathological features, but susceptibility to diet-induced pathological alterations may vary with age and strain. This study aimed to investigate age-dependent susceptibility to high-cholesterol-diet-induced AD-like alterations in white-haired and black-eyed (WHBE) rabbits using a multimodal approach. Compared with the normal control group (NC), juvenile rabbits (2 months old) in the 2% high-cholesterol diet (CD) group showed disturbed plasma lipid and glucose metabolism, increased body weight, and reduced encephalization quotient (EQ). Neuropathologically, juvenile CD rabbits exhibited enhanced hippocampal Tau hyperphosphorylation and Aβ deposition. MRI demonstrated significant hippocampal atrophy and lateral ventricular enlargement, while [1]H-MRS revealed significant reductions in hippocampal N-acetylaspartate/Cr, glutamate (Glu)/Cr, and glycerophosphocholine (GPC)+phosphocholine (PCH)/Cr ratios. In the overall cohort, Tau protein expression was negatively correlated with (Glu+Gln)/Cr (rho = -0.50, P = 0.0096) and positively correlated with (GPC+PCH)/Cr (rho = 0.42, P = 0.0167), although these correlations lost significance after FDR correction in subgroup analyses. Additionally, Aβ expression was negatively correlated with age in pooled WHBE rabbits (rho = -0.35, P = 0.0437), with no significant metabolite correlations observed after multiple testing correction. Multiple linear regression further confirmed a significant 'Diet×Age' interaction for both Tau and Aβ, indicating the pathological effect of high-cholesterol diet was most prominent in juvenile animals. These findings suggest that juvenile WHBE rabbits are more vulnerable to high-cholesterol-diet-induced AD-like changes. This study provides a multimodal reference for optimizing rabbit AD models and exploring age-related neurodegenerative vulnerability.},
}

@article {pmid42486379,
year = {2026},
author = {LeFevre, JD and Robb, WH and Liu, D and Jackson, TB and Pechman, KR and Shashikumar, N and Vyas, Y and Landman, BA and Davis, LT and Hohman, TJ and Jefferson, AL},
title = {A comparative evaluation of multiple enlarged perivascular space segmentation tools.},
journal = {Magnetic resonance imaging},
volume = {},
number = {},
pages = {110749},
doi = {10.1016/j.mri.2026.110749},
pmid = {42486379},
issn = {1873-5894},
abstract = {BACKGROUND: Enlarged perivascular spaces (ePVS) are a marker of cerebral small vessel disease, potentially reflecting reduced waste clearance. Because manual quantification is unfeasible in large datasets, we developed and evaluated an automated tool.

METHODS: Detection Of Regions of Enlarged perivascular Spaces (DORES), a 3D nnU-Net-based deep learning algorithm was developed for ePVS segmentation using T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging (MRI). DORES was developed in two stages: an initial model trained on 35 manually segmented scans and a final model on 1460 pseudo-labeled sessions from the Vanderbilt Memory and Aging Project (VMAP). A subset of VMAP participants with 3 T brain MRI underwent whole-brain manual ePVS tracing (n = 35, 73 ± 9 years, 51% male) and visual rating (n = 388, 71 ± 8 years, 54% male) by a neuroradiologist. DORES was evaluated and compared against three other segmentation tools using Dice and F1 scores, absolute volume and element differences, correlation, and agreement. External validation used an Alzheimer's Disease Neuroimaging Initiative 3 subset with manual tracings (ADNI3, n = 18, 73 ± 9 years, 67% female).

RESULTS: DORES achieved Dice scores of 0.61 ± 0.16 (white matter) and 0.72 ± 0.08 (basal ganglia) in VMAP, with strong correlations and agreement for ePVS count and volume. Performances modestly declined in ADNI3 across algorithms. Scanner-stratified analyses showed stronger correlations for Philips versus Siemens images in the basal ganglia, indicating scanner-dependent differences in measurement consistency.

CONCLUSIONS: DORES provides a multimodal nnU-Net-based pipeline for ePVS segmentation in older adults. The model demonstrates robust within-cohort performance and reasonable external validity, though scanner-related effects limit application across sites.},
}

@article {pmid42486551,
year = {2026},
author = {Supuran, CT and Capasso, C},
title = {Carbonic anhydrases I and II.},
journal = {The Enzymes},
volume = {59},
number = {},
pages = {29-67},
doi = {10.1016/bs.enz.2026.06.005},
pmid = {42486551},
issn = {0423-2607},
mesh = {Humans ; *Carbonic Anhydrase Inhibitors/pharmacology/therapeutic use/chemistry ; Animals ; *Carbonic Anhydrase II/metabolism/antagonists & inhibitors/chemistry/genetics ; *Carbonic Anhydrase I/metabolism/antagonists & inhibitors/chemistry/genetics ; },
abstract = {Carbonic anhydrase (CA, EC 4.2.1.1) isoforms I (CA I) and II (CA II) are widespread cytosolic proteins in most vertebrates. They are abundant in the red blood cells and many other tissues, being involved in physiological processes such as pH regulation, CO2/bicarbonate homeostasis, respiration, and secretion of electrolytes rich in acid or bicarbonate in the stomach, kidneys, cerebrospinal fluid, eyes, and bones. The genetics, biochemistry, expression, localization in tissues and organs, kinetic properties, and catalytic mechanisms of these enzymes are well understood at the molecular level. At least five different inhibition mechanisms were described with more than 50 chemotypes acting as inhibitors. The activation with amine/amino acid activators was also well studied. The physiological role of CA I is poorly understood, whereas CA II is a physiologically dominant isoform, playing crucial functions in a host of tissues/organs. Interfering with its activity by means of inhibitors has been and is currently exploited in therapy for the management of edema, glaucoma, epilepsy, obesity, acute mountain sickness, and idiopathic intracranial hypertension. Promising preclinical data pointed to the potential use of CA II inhibitors for the management of other conditions, such as neuropathic pain, cerebral ischemia, rheumatoid arthritis, Alzheimer's disease, osteoporosis, and obstructive sleep apnea. Many CA inhibitors are in clinical use for the management of such conditions, among which are acetazolamide, thiazides and high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, and antiepileptics such as sulthiame, topiramate and zonisamide, whereas SLC-0111 is in clinical development as an antitumor agent. CA activators are not yet used clinically, but they might have pharmacological applications in the management of neurodegeneration, emotional memory disorders, obsessive-compulsive disorders, phobias, generalized anxiety, and post-traumatic stress. Finding novel modulators of activity for these enzymes may lead to innovative therapeutic applications and deepen our understanding of enzymes, their inhibitors, and their activators.},
}

Humans
*Carbonic Anhydrase Inhibitors/pharmacology/therapeutic use/chemistry
Animals
*Carbonic Anhydrase II/metabolism/antagonists & inhibitors/chemistry/genetics
*Carbonic Anhydrase I/metabolism/antagonists & inhibitors/chemistry/genetics

@article {pmid42486687,
year = {2026},
author = {Fang, Q and Guo, Y and Chen, L and Li, Y and Cai, Q and Zhang, J and Ma, X and Zeng, Y and Bai, G},
title = {A multimodal machine learning model integrating plasma biomarkers and MRI metrics for non-invasive prediction of amyloid-β pathology in mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261465672},
doi = {10.1177/13872877261465672},
pmid = {42486687},
issn = {1875-8908},
abstract = {BackgroundAccurate, non-invasive prediction of cerebral amyloid-β (Aβ) pathology in mild cognitive impairment (MCI) remains challenging yet critical for early intervention.ObjectiveTo develop a multimodal machine learning model integrating clinical features, plasma biomarkers, and structural MRI metrics for non-invasive Aβ prediction.MethodsData were obtained from the Alzheimer's Disease Neuroimaging Initiative. Participants with concurrent plasma biomarkers, 3D T1-weighted MRI, and amyloid assessments were included. Logistic Regression, Decision Tree, and Support Vector Machine models were constructed using clinical, plasma, MRI, and combined features. Performance was evaluated via internal validation and external testing in a cognitively unimpaired cohort using AUC, calibration curves, and decision curve analysis. The prognostic value of the model-derived Aβ risk probability was assessed using Cox regression in an independent longitudinal MCI cohort.ResultsThe optimal Logistic Regression model incorporated APOE ε4 status, Mini-Mental State Examination score, plasma p-Tau217, Aβ42/Aβ40 ratio, and bilateral hippocampal and left amygdalar volumes. The combined model achieved an AUC of 0.875 in internal validation and maintained robust performance in the external unimpaired cohort (AUC = 0.883), outperforming single-modality models. The predicted Aβ-positive risk probability effectively stratified disease progression risk in MCI patients (C-index = 0.771).ConclusionsA multimodal model integrating plasma and MRI features accurately predicts Aβ pathology and progression risk, offering a practical non-invasive tool for early Alzheimer's disease screening and risk stratification.},
}

@article {pmid42486877,
year = {2026},
author = {Kurz, C and Wüsten, NC and Tegethoff, P and Taute, M and Kehrls, M and Hufnagel, A and de Jonge, S and Deckert, A and Suchsland, MZ and König, A and Feustel, E and Heindl, P and Mattke, S and Perneczky, R},
title = {Adaptive pathways for multimodal community-based detection of cognitive impairment: the CogScreen I study.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42486877},
issn = {2045-2322},
mesh = {Humans ; *Cognitive Dysfunction/diagnosis/blood ; Biomarkers/blood ; Female ; Aged ; Male ; Surveys and Questionnaires ; Dementia/diagnosis ; Aged, 80 and over ; Early Diagnosis ; Independent Living ; Amyloid beta-Peptides/blood ; },
abstract = {Early detection of cognitive impairment is essential for dementia prevention and timely care. However, implementation in primary care and community settings remains limited. Building dementia-prepared health systems requires scalable and adaptive pathways that integrate subjective, digital and biological indicators, while accounting for heterogeneity in risk, education and age. CogScreen I was a cluster-randomized trial conducted in Munich senior centers from March 2023 to March 2024. Recruitment focused on community-dwelling adults aged ≥ 60 years reporting subjective cognitive concerns. Centers were randomized to: (A) the Subjective Cognitive Decline Questionnaire (SCD-Q) only, (B) SCD-Q plus digital cognitive testing, or (C) SCD-Q plus digital testing plus blood biomarkers (Aβ1-42/1-40, pTau181, GFAP, NfL). The primary endpoints were feasibility and acceptability, assessed through structured questionnaires and follow-up interviews with participants and general practitioners. Secondary endpoints examined latent cognitive structures and biomarker associations. Exploratory factor and clustering analyses revealed multimodal subgroups across subjective, digital, and biological measures, which informed a hypothesis-generating three-tier adaptive detection framework (low, medium, high intensity). Among the 473 participants (mean age 74.1 ± 7.6 years; 66% female; 63% with tertiary education), both feasibility and acceptability were high: Participants described the assessments as personally relevant, clearly communicated, and medically meaningful, and appreciated the added value of digital testing and biomarkers. Digital cognitive testing and biomarkers captured distinct latent dimensions of learning/working memory, psychomotor attention, and glial and amyloid pathology. Exploratory multimodal clustering identified three dementia risk profiles-low concern, intermediate, and at risk-which informed an adaptive, tiered detection model. Notably, subjective cognitive concerns assessed by the SCD-Q were strongly associated with overall subjective symptom burden, supporting the use of brief self-report questionnaires as a pragmatic and scalable first-step stratification approach in community-based dementia detection. Community-based, tiered detection pathways for cognitive decline are feasible, acceptable, and meaningful to older adults. Exploratory multimodal profiling suggests that combining subjective, digital, and biological measures may support individualized assessment strategies. However, limited GP engagement highlights the need for stronger integration with primary care to ensure downstream diagnostics and prevention pathways. The proposed framework remains hypothesis-generating and requires prospective validation.Clinical trials registeredCogScreen has been registered at clinical trials (NCT06191952, 2023-12-20).},
}

Humans
*Cognitive Dysfunction/diagnosis/blood
Biomarkers/blood
Female
Aged
Male
Surveys and Questionnaires
Dementia/diagnosis
Aged, 80 and over
Early Diagnosis
Independent Living
Amyloid beta-Peptides/blood

@article {pmid42487022,
year = {2026},
author = {Xu, W and Chen, J and Zhou, Y and Liu, C and Han, Y and Zheng, K},
title = {Comparative efficacy and safety of photobiomodulation, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation in Alzheimer's disease: a network meta-analysis of randomized controlled trials.},
journal = {Lasers in medical science},
volume = {41},
number = {1},
pages = {},
pmid = {42487022},
issn = {1435-604X},
support = {82371442//National Natural Science Foundation of China/ ; 2020YFC2004803//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Alzheimer Disease/therapy ; *Transcranial Direct Current Stimulation/adverse effects/methods ; *Transcranial Magnetic Stimulation/adverse effects/methods ; Randomized Controlled Trials as Topic ; *Low-Level Light Therapy/adverse effects/methods ; Treatment Outcome ; Cognition ; Cognitive Enhancement ; Bayes Theorem ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which current pharmacological therapies provide only modest and transient benefits, underscoring the need for effective non-pharmacological interventions. Non-invasive brain stimulation (NIBS), including photobiomodulation (PBM), transcranial direct current stimulation (tDCS), and repetitive transcranial magnetic stimulation (rTMS), is a promising approach. This study compared the efficacy, feasibility, and safety of PBM, tDCS, and rTMS in AD. We conducted a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs), prospectively registered in PROSPERO (CRD420251006868) and reported according to PRISMA-NMA. The primary outcome was global cognitive performance, assessed by the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were feasibility and safety, evaluated by dropout rates and adverse events, respectively. A total of 34 studies, comprising 35 RCTs (n = 1,559), were included, with one study contributing two independent randomized controlled trials. All three interventions improved global cognitive performance compared with control. PBM showed the highest estimated effects on both MMSE (MD = 3.14, 95% CrI: 1.71 to 4.60) and ADAS-Cog (MD = - 8.01, 95% CrI: -12.82 to - 3.13). In indirect comparisons, PBM was superior to rTMS for ADAS-Cog (MD = - 5.24, 95% CrI: -10.23 to - 0.12), while the MMSE comparison narrowly missed statistical significance (MD = 1.57, 95% CrI: -0.02 to 3.18). These findings were generally consistent across subgroups stratified by baseline cognition and intervention duration. PBM tended to rank highest for cognitive improvement with feasibility and safety comparable to tDCS and rTMS in AD. These findings support the therapeutic potential of PBM, and large-scale RCTs are needed to guide individualized treatment strategies, with implications for clinical decision-making in geriatric care.},
}

Humans
*Alzheimer Disease/therapy
*Transcranial Direct Current Stimulation/adverse effects/methods
*Transcranial Magnetic Stimulation/adverse effects/methods
Randomized Controlled Trials as Topic
*Low-Level Light Therapy/adverse effects/methods
Treatment Outcome
Cognition
Cognitive Enhancement
Bayes Theorem

@article {pmid42487135,
year = {2026},
author = {Waghmare, SG and Krishna, MM and Maccoux, EC and Franitza, AL and Link, BA and E, L},
title = {Functional analysis of late-onset Alzheimer's disease risk genes in Caenorhabditis elegans identifies regulators of neuronal aging.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42487135},
issn = {2047-9158},
support = {5520760//Advancing a Healthier Wisconsin Endowment/ ; 5520482//Advancing a Healthier Wisconsin Endowment/ ; AG087390/NH/NIH HHS/United States ; },
}

@article {pmid42487153,
year = {2026},
author = {Magalhães, TNC and Casseb, RF and Moraes, AS and Teixeira, CVL and Carletti, AM and De Rezende, TJR and Joaquim, HPG and Talib, LL and Forlenza, O and Cendes, F and Balthazar, MLF and Teunissen, CE},
title = {Relation of fluid neurodegeneration biomarkers with white matter integrity in Alzheimer's disease patients in Latin America.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261467065},
doi = {10.1177/13872877261467065},
pmid = {42487153},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is increasingly prevalent in Latin America. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising biomarkers of neurodegeneration, but their relationship with white matter (WM) integrity remains unclear.ObjectiveTo investigate associations between fluid neurodegeneration biomarkers and WM microstructure in a Brazilian cohort of individuals across the AD continuum and cognitively healthy controls.MethodsNinety-one participants were included: 27 cognitively healthy controls (mean age = 68.3 ± 5.2 years) and 64 amyloid-positive individuals with mild cognitive impairment or AD dementia (mean age = 70.6 ± 6.9 years). AD participants were characterized by low cerebrospinal fluid (CSF) Aβ42 concentrations (<540 pg/mL) and altered Aβ42/p-Tau and Aβ42/t-Tau ratios. Serum and CSF concentrations of NfL and GFAP were measured using single-molecule array technology and examined in relation to diffusion tensor imaging metrics, including fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity (AxD).ResultsWithin the clinical AD group, higher serum NfL levels were associated with lower AxD in the left cingulum tract (r = -0.372, p = 0.007). In cognitively healthy controls, serum NfL showed positive correlations with AxD and mean diffusivity in the right cingulum (r = 0.650, p = 0.001 and r = 0.607, p = 0.003, respectively). No significant associations were observed between serum or CSF GFAP concentrations and diffusion tensor imaging metrics.ConclusionsSerum NfL was associated with anatomically specific WM microstructural changes, with differing patterns across clinical groups.},
}

@article {pmid42487190,
year = {2026},
author = {Aschenbrenner, DS},
title = {Antidepressant is approved to treat agitation in Alzheimer disease.},
journal = {The American journal of nursing},
volume = {126},
number = {8},
pages = {18-19},
doi = {10.1097/AJN.0000000000000354a},
pmid = {42487190},
issn = {1538-7488},
}

@article {pmid42487544,
year = {2026},
author = {Zhou, J and Li, S and Liu, H and Sun, Y and Wang, Z},
title = {The Effectiveness of Animal-Assisted Interventions for People Living With Dementia: An Overview of Systematic Reviews and Meta-Analysis.},
journal = {International journal of nursing practice},
volume = {32},
number = {4},
pages = {e70172},
pmid = {42487544},
issn = {1440-172X},
support = {72274007//National Natural Science Foundation of China/ ; LJRC22YB03//Incubation Fund for Scientific Research and Innovation of Leading Talents of Unnamed Nursing of Peking University/ ; XJRC-2025-JY-YJ-GX-QNQZ-068//Xinjiang Talent Development Fund/ ; },
mesh = {*Dementia/therapy/psychology ; Humans ; *Animal Assisted Therapy ; Animals ; Quality of Life ; Systematic Reviews as Topic ; Activities of Daily Living ; },
abstract = {AIMS: This overview aims to provide high-quality evidence synthesis of animal-assisted interventions (AAIs) among people living with dementia.

BACKGROUND: Dementia has become the seventh leading cause of death in the world. Unfortunately, currently effective pharmacological interventions remain elusive. As a non-pharmacological treatment, AAI is gaining more attention while the effectiveness of AAI for people living with dementia remains unclear.

METHODS: EMBASE, PubMed, Cochrane Library, CINAHL, CNKI, VIP, CBM and Wanfang databases were searched from inception to March 2026. The AMSTAR2 was used to assess the methodological quality of the included reviews. Meta-analysis was conducted using STATA 16 for the original studies identified from the included reviews. Evidence quality of main outcomes was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines.

RESULTS: Sixteen systematic reviews were included in the overview. A significant improvement was found in depression among dementia patients, but not in agitation, quality of life (QOL), cognition and activities of daily living (ADL).

CONCLUSIONS: There is moderate evidence that AAI has positive effects on depression for people living with dementia. Despite searches, no sufficient evidence has been found to substantiate the positive effects of AAI on other outcomes in people living with dementia. Due to the small number of studies, small sample sizes and significant heterogeneity, more randomised controlled trials with large samples are needed.},
}

*Dementia/therapy/psychology
Humans
*Animal Assisted Therapy
Animals
Quality of Life
Systematic Reviews as Topic
Activities of Daily Living

@article {pmid42487594,
year = {2026},
author = {Lonlab, K and Nitjapol, A and Thummayot, S and Tiyaboonchai, W and Jumnongprakhon, P},
title = {Targeting Aβ25-35-Induced Neuronal Senescence-Like Features Using Curcumin-Loaded Solid Self-Emulsifying Drug Delivery Systems.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098440081260430205824},
pmid = {42487594},
issn = {1874-6128},
abstract = {INTRODUCTION: Curcumin is widely recognized for its anti-neurodegenerative properties. However, its clinical utility is hindered by poor aqueous solubility and low bioavailability. To address these limitations, Curcumin-loaded Solid Self-Emulsifying Drug Delivery Systems (C-SSEDDS) have been formulated to improve pharmacokinetics and neuronal targeting. Despite these advancements, the molecular mechanisms underlying curcumin in Alzheimer's Disease (AD)-related neuronal senescence remain poorly understood. Therefore, this study provides novel molecular insights into the therapeutic potential of C-SSEDDS for targeting neuronal senescence- like features in the AD context.

METHODS: An in vitro model of neuronal senescence-like features was established by exposing SK-N-SH cells to 0.075 μM Aβ25-35 for 24 hours, resulting in a 20-30% decline in cell viability. Subsequently, cells were post-treated with C-SSEDDS at optimized non-toxic concentrations (0.1, 1, and 10 μg/mL curcumin equivalent) and 10 μg/mL commercial curcumin for 24, 48, and 72 hours in Aβ25-35-free media. The study comprehensively assessed cell viability, morphological alterations, and key biomarkers associated with neuronal senescence-like features, including senescence- associated beta-galactosidase (SA-β-gal) positive cells, Reactive Oxygen Species (ROS) levels, NLRP3, Sirt-1, and synaptophysin expression.

RESULTS: C-SSEDDS post-treatment significantly improved cell viability, reduced apoptotic cells, and decreased SA-β-gal positive cells in Aβ25-35-induced senescence-like SK-N-SH cells compared to the untreated Aβ25-35 group. It also effectively decreased intracellular ROS level and NLRP3 expression, and markedly upregulated Sirt-1 and synaptophysin expression. Notably, CSSEDDS demonstrated therapeutic efficacy superior to commercial curcumin and comparable to N-acetylcysteine (NAC).

DISCUSSION: In SK-N-SH cells exhibiting senescence-like features, the C-SSEDDS formulation effectively counteracts Aβ25-35-induced damage. It mitigates key drivers of cellular stress, including oxidative stress, inflammation-related markers, and apoptosis, while also enhancing Sirt-1 activity and promoting synaptic plasticity.

CONCLUSION: C-SSEDDS demonstrates significant potential as a promising therapeutic strategy against Aβ25-35 -induced neuronal stress and senescence-like changes in AD.},
}

@article {pmid42488138,
year = {2026},
author = {Magee, RG and Li, Y and Rovine, MJ and Pelak, VS and Hamedani, AG},
title = {Epidemiology of visuospatial impairment in older adults: the Harmonized Cognitive Assessment Protocol.},
journal = {Innovation in aging},
volume = {10},
number = {8},
pages = {igag059},
pmid = {42488138},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: This study aimed to determine the prevalence of visuospatial impairment in a nationally representative sample of older adults and identify self- and informant-reported functional measures associated with visuospatial dysfunction.

METHODS: We analyzed data from 3496 participants aged ≥65 years in the 2016 Harmonized Cognitive Assessment Protocol (HCAP), a sub-study of the Health and Retirement Study. Visuospatial function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease constructional praxis and Mini Mental State Examination pentagon copy tasks. Impairment was defined as a factor score >1.5 SDs below expected relative to a robust normative sample. Cognitive status was classified by HCAP as normal, mild cognitive impairment (MCI), or dementia. Logistic regression models examined associations between visuospatial impairment and functional outcomes, adjusting for demographic, health, and general cognitive factors.

RESULTS: Visuospatial impairment was present in 435 participants (11.33%). Among these, 49.85% had MCI, and 39.97% had dementia. Over half of those with MCI and visuospatial impairment had no other cognitive domain affected. Visuospatial impairment was associated with increased odds of self-reported visual difficulty (OR 1.60, 95% CI: 1.20-2.15), difficulty using a map (OR 3.35, 95% CI: 2.35-4.80), and informant-reported navigation difficulties, including getting lost at home (OR 17.30, 95% CI: 8.02-37.31). Associations with driving, map use, and getting lost at home remained significant after adjusting for general cognition.

DISCUSSION AND IMPLICATIONS: Visuospatial impairment is common among older adults, frequently occurs in isolation in MCI, and is strongly associated with functional limitations, particularly in navigation and driving.},
}

@article {pmid42488179,
year = {2026},
author = {Taheri, H and Musaie, F and Mohammadzadeh, N and Tavassoli Naini, P and Novin, N and Salimi, O and Amini, A and Malekpour, H and Panahiyan, P and Malek, M and Fathiazar, A and Namadkolahi, R},
title = {Optimizing Alzheimer's prediction with dental care: comparing robust deep learning models in health and retirement study of America.},
journal = {American journal of neurodegenerative disease},
volume = {15},
number = {2},
pages = {16-24},
pmid = {42488179},
issn = {2165-591X},
abstract = {BACKGROUND: Previous research has illustrated links between dental care and Alzheimer's disease, the aim of this study was to examine whether dental care variables can enhance Alzheimer's risk prediction using two models including Long Short-Term Memory (LSTM) and Temporal Convolutional Network (TCN) models with health and retirement study data.

METHODS: 9,979 HRS participants without cognitive impairment were analysed in this study (mean age 67 years; and 59.8% female, waves 11-15: 2006/2008-2016). Analysis included 52 predictors including demographic, genetic (APOE ε4), health (including dental visit frequency), and psychosocial domains. The outcomes as cognitive impairment and dementia were defined by Langa-Kabeto-Weir criteria. Class imbalance was addressed by SMOTE and missing data were mean imputed. We standardized and reshaped features into five-wave temporal sequences. Data were split into 3 sets: 70% training, 10% validation, and 20% test. LSTM (single layer, 64 units) and TCN (two dilated convolutional layers, 32 channels) models were trained for up to 50 epochs using binary cross-entropy loss with Adam optimizer, learning-rate reduction on plateau, and early stopping based on validation F1. The accuracy, precision, recall, F1, and AUC-ROC were evaluated via Five-fold stratified cross-validation; the optimization of classification thresholds was done by maximizing F1. McNemar's test compared final predictions.

RESULTS: It was evident that LSTM consistently outperformed TCN as demonstrated by the following results: test accuracy 99.78% vs 79.01%; AUC-ROC 99.95% vs 92.74%; F1-score 99.67% vs 75.27%. Cross-validation consistency (LSTM F1 ~99.6%±0.1% vs TCN ~76.6%±1.5%) and stable validation-test metrics (final validation loss 0.0136 vs 0.3312) showed robust LSTM performance without overfitting. moreover, McNemar's test showed a significant difference (statistic = 2605.36; P<0.001). models with dental care variables showed high sensitivity (~99.8%).

CONCLUSIONS: Enhancement in Alzheimer's disease risk prediction in older adults was evident when incorporating dental care variables in LSTM-based sequential modeling which suggest potential for early detection. However, further studies in diverse populations and assessment of feature importance is necessary because of reliance on self-reported dental care data and the study's HRS-specific sample.},
}

@article {pmid42488183,
year = {2026},
author = {Singhal, M and Lin, J and Delehanty, M and Karimi, A and Rittner, L and Bento, M},
title = {Geographic and demographic gaps in publicly available Alzheimer's disease datasets: A large language model-based discovery and analysis.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076261470698},
pmid = {42488183},
issn = {2055-2076},
abstract = {INTRODUCTION: Alzheimer's disease (AD) affects millions worldwide, and researchers heavily rely on datasets for diagnosis and treatment. Identifying relevant datasets is challenging due to data gaps and bias related to the demographics and geographic origin.

METHOD: We investigated AD data gaps by identifying and manually curating publicly accessible AD datasets containing imaging and/or tabular data. We also extracted key information such as data availability, geographic location, and participant demographics. We used five Large Language Models (LLMs) to identify AD datasets, allowing us to explore potential datasets while also evaluating retrieval consistency across models.

RESULT: We identified 24 publicly accessible AD datasets (open access or controlled access via registration). These datasets enabled us to emphasize three critical gaps: (1) variability in AD dataset retrieval, as observed through differences in LLM outputs, related to dataset visibility and accessibility; (2) geographical imbalance, with North America contributing 55.6% of datasets, US alone 66.7%, followed by Europe at 36.1%, and smaller shares from South America 11.1%, Asia 8.3%, and Africa 2.8%; and (3) demographic deficits, with the majority of datasets predominantly White, as 9 of 24 had over 80% White participants. Among the seven datasets that reported any Black participant representation, the proportion of Black participants ranged from 15.3% to 18.8%.

CONCLUSION: These findings reveal significant disparities in the availability and retrieval of AD datasets, with most data concentrated in Western countries and critical gaps in demographic representation. LLMs show inconsistent retrieval, particularly for newer, smaller, or region-specific datasets, which may perpetuate existing biases.},
}

@article {pmid42488212,
year = {2026},
author = {Li, Z and Ming, Q and Fu, L and Yang, J and Lv, Y and Chen, B and Lu, Z},
title = {Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1886340},
pmid = {42488212},
issn = {2296-861X},
abstract = {Alzheimer's disease is increasingly viewed as a disorder in which age-related disturbances in microglial metabolism and the handling of nutritional substrates contribute to progressive loss of protective function. This review examines how lipids and ketone bodies shape microglial metabolic fitness in the aging brain and in Alzheimer's disease, and how these effects intersect with triggering receptor expressed on myeloid cells 2 (TREM2) signaling and translational biomarkers. Available evidence indicates that early compensatory glycolysis may give way to chronic bioenergetic failure, while cholesterol and lipoprotein trafficking, lipid droplet accumulation, ketone-body signaling, and TREM2-associated lysosomal pathways influence plaque engagement, phagocytosis, and inflammatory responses. The review also considers how apolipoprotein E genotype, brain region, sex, disease stage, and model system condition translation from experimental models to human disease. Fluid, imaging, and tissue readouts are therefore discussed as stage- and context-dependent proxies rather than fixed signatures. Overall, nutritional strategies and microglia-targeted interventions are most likely to be informative when aligned with disease stage and biological context.},
}

@article {pmid42488516,
year = {2026},
author = {Hajihosseini, S and Panahandeh, E and Rashidi, A and Soleimani, K and Parvandi, F and Rostami, N and Mottaghi, H and Rahmani, S and Belbasi, M and Bideshki, F and Faramin Lashkarian, M and Ebrahimi, MA and Alizadeh, H},
title = {Difficulty with taking medications and the future risk of Alzheimer's disease and related dementias: Health and Retirement Study of Americans.},
journal = {American journal of neurodegenerative disease},
volume = {15},
number = {1},
pages = {1-15},
pmid = {42488516},
issn = {2165-591X},
abstract = {BACKGROUND: This study aims to determine if self-reported issues with managing medication could be an early sign of cognitive decline, possibly pointing to a future diagnosis of Alzheimer's Disease and Related Dementias (ADRD). There is currently very little information available about the link between issues with medication management and the later diagnosis of an ADRD, despite the potential clinical importance of such a link.

METHODS: We analyzed Health and Retirement Study participants present and interviewed at Wave 11 (2012) and followed them through Wave 16 (2020). Medication-taking difficulty (R11MEDS) was classified as no difficulty/don't do vs. difficulty/can't do. Separate cohorts excluded prevalent dementia (R11DEMENE) or AD (R11ALZHEE). Incident outcomes were first respondent-reported physician diagnoses (RwDEMENE, RwALZHEE). Kaplan-Meier curves and multivariable Cox models estimated associations.

RESULTS: Of 18,878 dementia-free and 19,348 AD-free HRS respondents at Wave 11, 3.0-3.9% reported difficulty/could not take medications. Kaplan-Meier curves diverged early between exposure groups. In fully adjusted Cox models, medication-taking difficulty predicted higher hazards of incident all-cause dementia (HR 1.59, 95% CI 1.23-2.06) and AD (HR 1.57, 95% CI 1.09-2.27), with corroborating pooled logistic estimates.

CONCLUSION: Difficulty in Managing Medications is considered to be a robust prodromal indicator of ADRD, regardless of demographic influences. Therefore, the evaluation of an individual's ability to manage medications within routine assessment may represent a practical, costeffective means to identify cognitive decline and develop appropriate management strategies.},
}

@article {pmid42488555,
year = {2026},
author = {Zhao, Q and Li, S and Ju, Y and Kong, X and Liu, X},
title = {Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1791272},
pmid = {42488555},
issn = {2296-634X},
abstract = {Human pluripotent stem cell-derived brain organoids have emerged as a transformative platform for modeling Alzheimer's disease (AD), thus addressing long-standing translational obstacles posed by the disease's complex etiology and interspecies differences. This review systematically examines methodological advances in brain organoid technology, from basic fabrication and brain-region-specific organoids to multicellular assembloids that incorporate microglia and vascular components, with an emphasis on strategies for overcoming fetal-like phenotypes. We surveyed literature published between 2018 and April 2026 that focused on human iPSC-derived organoid models that recapitulate core AD pathologies, including Aβ plaques, tau tangles, neuroinflammation, and blood-brain barrier dysfunction. Key findings demonstrate that organoids effectively capture genotype-phenotype relationships for major AD genes (APP, PSEN1, PSEN2, and APOEε4), enable the dissection of signaling pathway dysregulation (Wnt/β-catenin), and when combined with CRISPR editing and single-cell multi-omics, reveal cell-type-specific disease mechanisms. Organoids have also been successfully applied to patient-specific "avatar" models and high-throughput drug screening, thus advancing precision medicine approaches. However, current technological bottlenecks-including a lack of functional vascularization, batch-to-batch variability, and insufficient standardization-limit the full recapitulation of chronic, age-dependent AD pathology. This review critically evaluates these limitations, addresses ethical considerations surrounding neural organoids, and looks forward to future integration with artificial intelligence, spatial omics, and multi-organ systems to accelerate the translation of organoid-based discoveries into clinical applications.},
}

@article {pmid42488639,
year = {2026},
author = {Zhao, X and Zhang, G and Wang, Z and Zhang, D and Xia, Z and Huo, C},
title = {Autoimmune signatures in neurodegenerative dementias: from peripheral immune activation to CNS pathology.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1893167},
pmid = {42488639},
issn = {1664-3224},
mesh = {Humans ; Animals ; *Dementia/immunology/pathology ; *Autoimmunity ; *Neurodegenerative Diseases/immunology/pathology ; Adaptive Immunity ; Autoantibodies/immunology ; *Central Nervous System/immunology/pathology ; T-Lymphocytes/immunology ; },
abstract = {Neurodegenerative dementias, including Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, and related tauopathies, are traditionally defined by protein aggregation, neuronal dysfunction, synaptic loss, and glial-mediated neuroinflammation. However, emerging evidence indicates that adaptive immunity may also contribute to disease heterogeneity and progression. These disorders should not be considered classical autoimmune diseases, but they may display autoimmune-like signatures, including neural antigen-specific T cell responses, clonal expansion of T cells in blood or cerebrospinal fluid, CNS infiltration of adaptive immune cells, and brain-targeting autoantibodies. Recent studies have linked α-synuclein-specific T cell reactivity to early Parkinson's disease, identified clonally expanded CD8[+] T cells in Alzheimer's disease cerebrospinal fluid, and provided direct evidence of adaptive immune involvement in Lewy body dementia, including altered peripheral immunophenotypes and CD4[+] T cell-associated neurodegenerative mechanisms. Experimental tauopathy models further show that microglia-mediated T cell infiltration can drive neurodegeneration. Humoral autoreactivity and progression-associated immune changes further suggest that adaptive immune profiles may help define biologically distinct dementia subgroups. In this mini review, we summarize evidence connecting peripheral immune activation, intrathecal adaptive immune remodeling, and CNS pathology in neurodegenerative dementias. We also discuss how longitudinal blood-CSF profiling, single-cell/TCR/BCR sequencing, autoantibody profiling, and mechanistic validation may clarify whether these immune signatures are pathogenic, compensatory, or bystander responses.},
}

Humans
Animals
*Dementia/immunology/pathology
*Autoimmunity
*Neurodegenerative Diseases/immunology/pathology
Adaptive Immunity
Autoantibodies/immunology
*Central Nervous System/immunology/pathology
T-Lymphocytes/immunology

@article {pmid42488724,
year = {2026},
author = {Liu, F and Huang, Y and Wang, A and Liu, P and Wu, H and Fan, H},
title = {BDNF-amyloid-β Axis in Alzheimer's disease: molecular mechanisms and therapeutic perspectives.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1884003},
pmid = {42488724},
issn = {1662-5099},
abstract = {Alzheimer's disease (AD), the most common cause of dementia in older adults, is characterized by progressive cognitive decline, synaptic dysfunction, and neuronal loss. Among the multifactorial mechanisms implicated in AD, reciprocal interactions between brain-derived neurotrophic factor (BDNF) and amyloid-β (Aβ) have attracted increasing attention as a convergent axis linking amyloid pathology to impaired neurotrophic support. BDNF promotes neuronal resilience, synaptic plasticity, and cognitive function primarily through the activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and downstream signaling pathways, including PI3K-Akt and MAPK/ERK. Human postmortem and biomarker studies mainly support associations between reduced BDNF signaling, synaptic dysfunction, and AD-related pathology. In contrast, cell-based and animal studies provide mechanistic evidence that BDNF/TrkB signaling may influence amyloid precursor protein (APP) processing and neuronal resistance to Aβ-induced stress. Conversely, mechanistic studies indicate that Aβ accumulation can suppress CREB-dependent BDNF expression, disturb BDNF transport, and impair TrkB receptor function. Thus, the BDNF-Aβ relationship is better interpreted as a stage- and context-dependent pathogenic coupling rather than a simple causal loop. This review synthesizes evidence from human studies, animal models, and cellular systems to clarify how BDNF-Aβ dysregulation contributes to AD progression and to discuss the translational potential of BDNF-oriented interventions.},
}

@article {pmid42488747,
year = {2026},
author = {Jiang, W},
title = {Pharmacological advances of honokiol: Mechanisms, targets and therapeutic potential (Review).},
journal = {Biomedical reports},
volume = {25},
number = {3},
pages = {103},
pmid = {42488747},
issn = {2049-9442},
abstract = {Honokiol (HKL), a bioactive biphenolic lignan isolated from the bark of Magnolia officinalis, possesses diverse pharmacological properties, including neuroprotective, antitumor, anti-inflammatory and metabolic regulatory effects. Despite its therapeutic promise, the clinical application of HKL is severely restricted by its hydrophobicity and low oral bioavailability. The present review systematically summarized 99 studies (90 original articles and nine reviews) on the pharmacological profile of HKL. It detailed HKL's molecular interactions with key signaling targets, such as sirtuin 3, NOD-like receptor family pyrin domain containing 3-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes, Yes-associated protein/transcriptional coactivator with PDZ-binding motif, adenosine monophosphate-activated protein kinase and signal transducer and activator of transcription 3, which underly its efficacy against cancer (ovarian, liver, breast, colorectal, and lung), neurodegeneration (Alzheimer's and Parkinson's disease), metabolic disorders (diabetes, nonalcoholic fatty liver disease and obesity) and inflammatory and infectious diseases. Furthermore, the present review critically evaluated recently developed strategies to overcome its pharmacokinetic limitations. The present review offered an updated theoretical basis for understanding the structure-activity relationship of HKL and provided insights into its translation from bench to bedside.},
}

@article {pmid42488757,
year = {2026},
author = {Jorge, L and Oliveira, J and Martins, R and Lopes, T and Quental, H and Castelo-Branco, M},
title = {Distinct brain regions are affected by neurodevelopmental or pre-dementia changes in Down syndrome.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag269},
pmid = {42488757},
issn = {2632-1297},
abstract = {Down syndrome, a condition characterized by triplication of chromosome 21, leads to a complex interplay between neurodevelopmental and dementia-related changes similar to the ones observed in Alzheimer's disease. Here we aimed to understand this interplay by using imaging biomarkers for different cognitive profiles in Down syndrome, and by analysing early developmental differences versus age-related changes. We analysed voxel-based morphometric measures of grey matter volume from high-resolution T1-weighted MRI in 23 adults with Down syndrome (18-59 years, five female) in preclinical/prodromal stages of Alzheimer's disease and 24 age- and sex-matched controls, along with cognitive assessments. Neuroanatomical group differences were assessed using two-sample t-tests. Age-related effects on brain integrity, and cognitive function were examined through voxel-wise regression analyses and correlation tests, respectively. Finally, structural correlates of episodic memory were explored across the whole brain at the voxel level within the Down syndrome group. Results revealed a neuroanatomic phenotype with both regional increases and decreases in grey matter volume compared to controls (false discovery rate, q ≤ 0.05). Based on regression analysis, we found the following patterns in regions that were differentially reduced in Down syndrome: same intercept and different age-related slope (defining specific age-related differences), different intercept (implying initial neurodevelopmental differences) and same slope (signalling no age-related differences). A notable example of the first was the left hippocampus and its subfields, and of the second was the orbitofrontal cortex. Follow-up whole brain analyses confirmed age-related changes in Down syndrome (false discovery rate, q ≤ 0.05) in the parietal and temporal cortices, extending into hippocampus, as compared to controls, independent of neurodevelopmental (non-age related) features, and most pronounced in the right hemisphere. Episodic and associative memory declined significantly with age (P = 0.016) in Down syndrome and correlated with shrinkage in regions vulnerable to Alzheimer's disease (P < 0.01), including the precuneus and posterior cingulate cortex. Our findings suggest that individuals with Down syndrome undergo early brain atrophy that occurs independently of baseline neurodevelopmental changes, particularly in the hippocampus and temporoparietal regions. Notably the posterior cingulate cortex and precuneus showed an association with episodic memory loss, a pattern that is consistent with Alzheimer's Disease. In sum we found a dichotomic distinction between brain regions affected by developmental or ageing changes in Down syndrome.},
}

@article {pmid42488758,
year = {2026},
author = {Krohn, F and Sarkar, M and Schütze, H and Iliopoulos, P and Penalba-Sánchez, L and Hämmerer, D and Yakupov, R and Lüsebrink, F and Spottke, A and Schneider, A and Roy, N and Incesoy, E and Heneka, M and Kilimann, I and Kleineidam, L and Teipel, SJ and Brosseron, F and Goerss, D and Glanz, W and Schmid, M and Rostamzadeh, A and Wagner, M and Fliessbach, K and Jessen, FO and Düzel, E and Betts, MJ},
title = {Substantia Nigra MRI markers are lower in Alzheimer's disease and are linked to general cognitive function.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag238},
pmid = {42488758},
issn = {2632-1297},
abstract = {Individuals with Alzheimer's disease dementia show Alzheimer's disease pathology and a heterogeneous degeneration of the Substantia Nigra (SN) post-mortem. However, it is unclear how SN degeneration is related to cognitive dysfunction across the Alzheimer's disease dementia continuum. In this study, using data from the prospective DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), we investigated whether in vivo SN MRI measures are lower in individuals with clinically defined Alzheimer's disease dementia than in healthy control subjects (HC) and if they are associated with hippocampal functional activity during the processing of novel visual stimuli and subsequent recognition memory. One hundred and sixty DELCODE participants (69 years ± 6 years, 88 men), including 79 HC, 70 individuals with subjective cognitive decline (SCD), 17 individuals with mild cognitive impairment (MCI) and 10 individuals with Alzheimer's disease dementia, completed a scene novelty and encoding task and a 3T SN-sensitive MRI scan, from which the two in vivo SN measures MRI contrast and volume were calculated and harmonized between scanner sites while preserving diagnostic group differences. For 71 individuals, CSF levels of phosphoTau, total tau and amyloid-beta 42/40 ratio (Aß42/40) were available. All individuals completed a neuropsychological task battery from which a global cognitive score was calculated. In separate models, we assessed the relationship between SN MRI markers and CSF levels of Alzheimer's disease, the global cognitive score, hippocampal novelty activation and recognition memory while accounting for age, sex, years of education and total intracranial volume (TIV). SN volume but not SN MRI contrast was lower in individuals with clinical Alzheimer's disease dementia [one-way analyses of covariance (ANCOVA); F(156,4) = 5.6665, P = 0.0010, n = 160]. SN MRI contrast and volume were not associated with Aß42/40, ptau and total tau CSF levels (all P > 0.1) or hippocampal novelty activation (all P > 0.1). Moreover, SN volume was positively associated with recognition memory (R [2] = 0.07, P < 0.001, n = 159), global cognition (R [2]= 0.38, P < 0.0001, n = 160) and years of education (R [2] = 0.03, P = 0.036, n = 160). Our study emphasizes the potential of using in vivo SN MRI markers to study the impact of SN degeneration on general cognitive impairment and recognition memory in an Alzheimer's disease dementia cohort. Our results motivate future longitudinal studies to explore how SN volume and SN contrast change with disease progression, how these are differentially associated with cognitive decline, and how SN volume and SN contrast might be related to other dopamine-dependent cognitive functions and dysfunctions.},
}

@article {pmid42489128,
year = {2026},
author = {Shen, Q and Chang, H and Li, J and Guo, H and Shi, W and Yan, Y and Ouyang, W and Zhang, Z and Wu, X and Xing, D and Yang, S},
title = {Photobiomodulation of immune crosstalk rescues neuroinflammation in Alzheimer's disease models.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag247},
pmid = {42489128},
issn = {1460-2156},
abstract = {Peripheral immune cell infiltration and crosstalk with brain-resident cells critically drive Alzheimer's disease (AD)-associated neuroinflammation, highlighting its therapeutic potential. Here, we found that photobiomodulation (PBM) markedly reduced cerebral CD8+ T cells infiltration in the cortex of AD (APP/PS1 and 3×Tg) mice, thereby improving cognition, and alleviating AD-related pathology by mitigating neuronal damage and gliosis. Immunofluorescence and transcriptomic analyses revealed that PBM inhibited the release of chemokines and pro-inflammatory cytokines from microglia, reducing endothelial adhesion molecules-mediated T cell migration. Concurrently, reduced secretion of tumor necrosis factor-α, interleukin-1α, and complement component 1q by pro-inflammatory microglia further diminished neurotoxic A1 astrocyte induction. Genetic overexpression or pharmacological inhibition further validated that PBM disrupted microglia NOD-like receptor protein 3 inflammasomes activation, attenuating astrocyte reactivity and T cells recruitment. These findings collectively suggest that the PBM-induced modulation of crosstalk between microglia, astrocytes, and CD8+ T cells is closely related to cognitive improvement. Reprogramming central-peripheral immune crosstalk with PBM resolves neuroinflammation and restores cognition in AD models-a translatable strategy for combating neurodegeneration.},
}

@article {pmid42489215,
year = {2026},
author = {Liu, C and Sakha, K and Anton, J and Cardenas-Rivera, A and Yaseen, MA},
title = {Prolonged systemic inflammation worsens impairments to astrocyte Ca[2+] and functional hyperemia in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71607},
doi = {10.1002/alz.71607},
pmid = {42489215},
issn = {1552-5279},
support = {//National Cancer Institute Cancer Center/ ; R01AA27097//Northeastern College of Engineering and the National Institutes of Health/ ; R56AG058849//Northeastern College of Engineering and the National Institutes of Health/ ; R21AG085655//Northeastern College of Engineering and the National Institutes of Health/ ; R01AA27097/AA/NIAAA NIH HHS/United States ; R56AG058849/AG/NIA NIH HHS/United States ; },
mesh = {Animals ; *Astrocytes/metabolism ; *Alzheimer Disease/metabolism/pathology/physiopathology ; Mice ; *Inflammation/metabolism ; Mice, Transgenic ; *Hyperemia/metabolism/physiopathology ; *Calcium/metabolism ; Disease Models, Animal ; Lipopolysaccharides ; Male ; Calcium Signaling ; *Neuroinflammatory Diseases ; },
abstract = {INTRODUCTION: Chronic neuroinflammation in Alzheimer's disease (AD) alters astrocyte physiology and neurovascular unit function. AD patients frequently experience recurrent systemic inflammatory insults from comorbid conditions, which act as "secondary-hits" believed to worsen cognitive decline. The impact of these secondary insults on astrocyte-mediated neurovascular regulation remains unknown.

METHODS: We applied intravital two-photon microscopy to longitudinally investigate astrocytic Ca[2] [+] dynamics and functional hyperemia during sensory stimulation in APP/PS1dE9 mice before and during secondary lipopolysaccharide (LPS)-induced systemic inflammation.

RESULTS: AD mice exhibited diminished stimulation-evoked astrocytic Ca[2] [+] activity, while functional hyperemia remained largely preserved. LPS further suppressed astrocytic Ca[2] [+] responses and produced temporally specific vascular alterations, with AD and wild-type mice following divergent inflammatory trajectories.

DISCUSSION: Our findings provide the first in vivo longitudinal characterization of how secondary systemic inflammation disrupts astrocyte-mediated neurovascular regulation. The selective vulnerability of astrocytic Ca[2] [+] signaling relative to vascular output implicates recurrent inflammatory insults as a clinically relevant contributor to neurovascular dysfunction in preclinical AD.},
}

Animals
*Astrocytes/metabolism
*Alzheimer Disease/metabolism/pathology/physiopathology
Mice
*Inflammation/metabolism
Mice, Transgenic
*Hyperemia/metabolism/physiopathology
*Calcium/metabolism
Disease Models, Animal
Lipopolysaccharides
Male
Calcium Signaling
*Neuroinflammatory Diseases

@article {pmid42489430,
year = {2026},
author = {Ishihara, K and Yasui, H and Harada, K and Amano, K and Saito, M and Kaneda, K and Katsuda, M and Kawashita, E and Hata, T and Annoura, R and Nishimura, K and Terasaki, R and Sago, H and Shimohama, S and Akiba, S and Yamakawa, K and Takata, K},
title = {Down syndrome-associated trisomic chromosomal regions modify amyloid-β accumulation and cause early death in a mouse model of aspects of Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469121},
doi = {10.1177/13872877261469121},
pmid = {42489430},
issn = {1875-8908},
abstract = {BackgroundIndividuals with Down syndrome (DS), caused by triplication of chromosome 21 (Hsa21), face a significantly increased risk of early-onset Alzheimer's disease (AD) and epilepsy. However, the specific impact of Hsa21 genes on these risks is not yet fully understood.ObjectiveTo investigate how triplication of mouse chromosome 16 (Mmu16), homologous to Hsa21, affects amyloid-β (Aβ) accumulation in the brain and epileptic seizures in AD-DS model mice.MethodsTo generate AD-DS model mice, we crossed a mouse model of aspects of AD-an APPswe/PS1[dE9] mouse exhibiting brain Aβ accumulation and sudden death associated with epileptic seizures with DS mouse models carrying an extra copy of partial segments of mouse chromosome 16. We used three DS model lines: Ts1Cje, harboring a triplicated region encoding ∼70 Hsa21-homologous genes (Scaf4-Zbtb21); Ts1Rhr with triplication of the Cbr3-Fam3b region; and a newly developed Ts1Kei mouse carrying an extra copy of the Scaf4-Cbr1 region. Aβ accumulation was assessed by immunohistochemistry and enzyme-linked immunosorbent assay.ResultsCompared with APPswe/PS1[dE9] mice, Aβ deposition and insoluble Aβ levels in the brain decreased in APPswe/PS1[dE9]-Ts1Cje mice but not in APPswe/PS1[dE9]-Ts1Rhr mice. The high mortality in APPswe/PS1[dE9] mice was suppressed by either Ts1Cje- or Ts1Rhr-triplicated region. Despite a tendency for decreased Aβ accumulation in APPswe/PS1[dE9]-Ts1Kei mice, the study could not be finished due to the extremely high mortality.ConclusionsThe trisomic region in Ts1Kei mice is suggested to harbor genes associated with decreased Aβ accumulation. Alternatively, the trisomic region in Ts1Rhr mice contains genes suppressing sudden death in APPswe/PS1[dE9] mice.},
}

@article {pmid42489432,
year = {2026},
author = {Custodio, B and Montesinos, R and Agüero, K and Huilca, JC and Verastegui, G and Bartolo, P and Nuñez-Huanca, M and Albujar Pereira, MF and Godoy, ME and Ibáñez, A and Custodio, N},
title = {Recruitment challenges and strategies for engaging the Peruvian population in the ReDLat Study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261467782},
doi = {10.1177/13872877261467782},
pmid = {42489432},
issn = {1875-8908},
abstract = {BackgroundRecruitment for Alzheimer's disease and related dementias research remains challenging, particularly when reaching underrepresented groups such as Latin Americans.ObjectiveThis study aimed to (1) assess recruitment rates across strategies in the ReDLat study and (2) discuss lessons learned to inform future recruitment practices.MethodsThis retrospective study outlines the recruitment for ReDLat, a multi-partner consortium expanding dementia research in Latin America. Participants were recruited using: printed flyers, social media, word-of-mouth, and professional referrals. At initial contact, participants were asked how they learned about the study. Enrollment rates were calculated for each source, and differences across sources were examined using a Pearson chi-square test.ResultsBetween January 2023 and March 2025, 577 individuals expressed interest, of whom 69% (n = 397) were enrolled. Enrollment rates differed significantly across sources (χ[2] (3) = 41.66, p < 0.001); professional referrals achieved a substantially higher rate (81%) than printed flyers (51%), social media (55%), and word-of-mouth (60%), which showed broadly comparable rates. Printed flyers and social media generated broad interest but lower enrollment conversion. Among the 180 individuals not enrolled, the most frequent reason for non-participation was failure to meet inclusion criteria (54%), particularly among those reached via social media and word-of-mouth. Loss of contact accounted for 36% of non-participation.ConclusionsProfessional referrals were associated with the highest enrollment rate for the ReDLat study. These findings highlight the importance of leveraging community trust and professional networks to improve recruitment outcomes for dementia research in underrepresented populations.},
}

@article {pmid42489435,
year = {2026},
author = {El Jaouhari, S and Geetan, C and Farousi, B and Pilli, LI and Neal, D and Engelsma, T and Vullings, I and Uysal-Bozkir, Ö and Van Deudekom, F and Muller, M and Vroomen, JM},
title = {Aging in place preferences of older adults with cognitive impairment and informal caregivers: A qualitative analysis of a discrete choice experiment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469138},
doi = {10.1177/13872877261469138},
pmid = {42489435},
issn = {1875-8908},
abstract = {BackgroundThe Netherlands spends more on long-term care than any other country. In 2015, reforms aimed to promote aging in place (AIP) but have been associated with increased crisis-related hospitalizations, rising caregiver burden, and a need for safer AIP strategies. Little is known about how people with dementia and informal caregivers prioritize AIP care and how their preferences differ.ObjectiveTo identify and compare AIP care preferences of people with dementia and informal caregivers, highlighting shared and individual priorities.MethodsWe used a think-aloud protocol within a discrete choice experiment (DCE). Participants were recruited from outpatient clinics, daycare centers, and cultural organizations. To ensure inclusivity, a formal dementia diagnosis was not required given documented diagnostic delays, particularly in migrant communities. Forty participants (20 care recipients, 20 informal caregivers) completed choice tasks comparing care packages. The DCE comprised three rounds: an online survey for informal caregivers, interviews with the person with dementia, and a dyadic round. Think-aloud responses illuminated decision-making; audio was transcribed verbatim and thematically analyzed.ResultsFive themes shaped preferences: (1) burden of in-home care and care planning, (2) role of case managers, (3) accessibility and inclusivity of social activities, (4) trust in healthcare providers, and (5) reimbursements for home adaptations. Care recipients prioritized in-home care and social activities; caregivers emphasized case management. Both valued emotional support and full reimbursements for home adaptations.ConclusionsTailoring AIP strategies to the distinct needs of both groups is essential and can support more equitable, effective AIP models.},
}

@article {pmid42489438,
year = {2026},
author = {Saadawy, M and Majeed, M and Saadawy, E and , },
title = {APOE4-specific glymphatic effects on clinical progression in the Alzheimer's Disease Neuroimaging Initiative with pathological correlates in the A4 study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469565},
doi = {10.1177/13872877261469565},
pmid = {42489438},
issn = {1875-8908},
abstract = {BackgroundThe APOE ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, some carriers show "clinical resilience", maintaining their cognition despite high risk.ObjectiveWe hypothesized that the glymphatic system, the brain's waste clearance pathway, may attenuate APOE ε4-mediated neurodegeneration, and tested this in two independent cohorts.MethodsWe analyzed 625 cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) discovery cohort and 447 amyloid-positive participants from the preclinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) validation cohort. Glymphatic function was estimated using the analysis of diffusional kurtosis imaging along the perivascular space (DTI-ALPS) index in ADNI and choroid plexus (CP) [18]F-Flortaucipir PET uptake in the A4 study. Primary outcomes were clinical conversion to dementia (ADNI) and hippocampal tau pathology (A4).ResultsIn the discovery cohort, we observed a trend toward ALPS × APOE4 interaction (p = 0.057, not reaching conventional statistical significance). Carriers with preserved function (high ALPS) showed a reduced conversion risk (hazard ratio = 0.52, 95% CI: 0.27-0.99) compared to those with low function. In the validation cohort, glymphatic interface dysfunction (higher CP tau) strongly predicted hippocampal tau burden (p < 0.0001). However, the gene-specific interaction was not replicated (p = 0.928); clearance failure predicted pathology regardless of genotype. Exploratory fluid biomarker analyses in ADNI did not reveal significant interactions.ConclusionsThese findings suggest that preserved glymphatic function is associated with clinical resilience in APOE ε4 carriers, though the interaction was borderline (p = 0.057) and should be considered hypothesis-generating. The strong pathological associations with clearance integrity highlight a biologically plausible mechanism in AD pathogenesis that warrants further investigation.},
}

@article {pmid42489439,
year = {2026},
author = {Szapary, CL and Syme, M and Lyons, KS and Monin, JK and Cornelius, T and Heffner, KL and Vranceanu, AM},
title = {"From theory to methodology": Evaluating a workshop for designing mechanistic interventions for dementia dyads.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261467779},
doi = {10.1177/13872877261467779},
pmid = {42489439},
issn = {1875-8908},
abstract = {Background: Coping with the challenges of Alzheimer's disease and related dementias is a shared experience, impacting individuals living with the disease, their care partners, and their relationship. As the number of people affected by dementia continues to rise, so does the demand for evidence-based psychosocial interventions that support the well-being of both members of the dyad. However, the current dyadic dementia intervention (DDI) landscape remains limited in scope and rigor, often lacking strong relational theoretical underpinnings and clear mechanisms of action. Objective: To address this gap, a four-hour workshop was offered at the 2024 Gerontological Society of America Annual Scientific Meeting to equip researchers with the knowledge, confidence, and skills necessary to conduct methodologically rigorous DDI studies. Methods: The first hour of the workshop included didactic presentations on dyadic theory, intervention design, statistics, and dementia-specific considerations. Attendees then participated in small-group, problem-based experiential activities, applying the learned content to their own research projects with individualized feedback from workshop leaders. Results: Participants, primarily from the disciplines of nursing, psychology, and the social sciences, reported significant improvements in perceived knowledge and confidence from pre- to post-workshop and rated the experience as highly satisfactory. Conclusions: These findings suggest that a workshop combining didactic instruction with experiential, problem-based learning is both feasible and effective in strengthening researchers' self-efficacy and skills to advance DDI research.},
}

@article {pmid42489441,
year = {2026},
author = {Drenth, N and van Dijk, SE and Hafkemeijer, A and Rombouts, SARB and van der Grond, J and van Rooden, S},
title = {Early cerebral amyloid angiopathy-related pathology is associated with localized functional brain connectivity.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469189},
doi = {10.1177/13872877261469189},
pmid = {42489441},
issn = {1875-8908},
abstract = {BackgroundThe mechanisms of early brain damage in cerebral amyloid angiopathy (CAA), a highly prevalent comorbid condition in Alzheimer's disease, are not completely understood. While current CAA diagnosis relies on late-stage MRI markers, impaired neurovascular coupling (NVC) has emerged as a promising early marker.ObjectiveTo investigate whether early vascular changes in CAA are associated with functional brain consequences, we examined the association between NVC and various functional connectivity metrics.MethodsWe analyzed MRI data from 93 older adults (71 ± 9 years old). A subgroup meeting Boston criteria v2.0 for possible or probable CAA (n = 46) was analyzed separately to investigate associations in confirmed CAA-related pathology. NVC (time to peak, time to baseline, and BOLD amplitude) was assessed in the occipital cortex using a visual stimulation task. Functional connectivity was assessed at multiple scales using resting-state fMRI, including within ten standard networks, between individual brain regions (edgewise analysis), and across the whole brain (graph theory).ResultsGeneral linear models, adjusted for age, sex, and clinical diagnosis, showed no significant associations between NVC and global connectivity metrics (networks and graph theory). Edgewise analyses revealed limited significant localized functional connections for each NVC measure. Findings were consistent across the total sample and the CAA subgroup.ConclusionsEarly CAA-related pathology is associated with localized rather than global functional connectivity. While large-scale connectivity remains preserved, edgewise analyses indicate subtle localized functional alterations. This suggests that functional connectivity disruption may originate as small-scale deficits that only progress into widespread, global impairment in advanced disease stages.},
}

@article {pmid42489442,
year = {2026},
author = {Keith, CM and Haut, MW and Worhunsky, P and Vieira Ligo Teixeira, C and Mehta, RI and Malone, J and Phelps, H and Ward, M and Miller, M and Pockl, S and Rajabalee, N and Marano, G and McCuddy, WT and D'Haese, PF and Rezai, A},
title = {Episodic memory and associated cortical atrophy in amnestic early-onset and late-onset Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469183},
doi = {10.1177/13872877261469183},
pmid = {42489442},
issn = {1875-8908},
abstract = {BackgroundMemory consolidation problems are often prototypical in Alzheimer's disease (AD). However, it remains undetermined whether episodic memory presents similarly in early-onset Alzheimer's disease (EOAD) relative to the more commonly occurring late-onset Alzheimer's disease (LOAD).ObjectiveThis study examined episodic memory and its neuroanatomical correlates in amnestic early-onset (aEOAD) relative to amnestic late-onset AD (aLOAD).MethodsUsing our single center data set obtained from a memory clinic setting (N = 180), we examined group differences in multiple markers of episodic memory along with associations with volume and thickness of underlying signature brain regions.ResultsWe did not observe any difference for examined measures of memory performance between aEOAD and aLOAD. Associations between episodic memory processes and volume and thickness of the brain regions examined were also largely similar, except for a stronger relationship between memory consolidation and thinner left supramarginal gyrus observed in the aEOAD group.ConclusionsOverall, the current results support similar memory consolidation processes in early- and late-onset amnestic Alzheimer's disease, though the parietal cortex may play a larger role in memory consolidation in aEOAD.},
}

@article {pmid42489457,
year = {2026},
author = {Liu, Y and Qiu, Q and Yue, L and Hong, B and Su, N and Li, W and Xiao, S and Sun, L and Chen, J and , },
title = {Precuneus amyloid-β deposition involving the association of irritability and cognitive decline: A multi-cohort longitudinal study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261467432},
doi = {10.1177/13872877261467432},
pmid = {42489457},
issn = {1875-8908},
abstract = {BackgroundIrritability is increasingly recognized for its association with cognitive function, though its impact on cognitive decline and underlying mechanisms remain unclear.ObjectiveTo investigate the associations between irritability and cognition, identify potential neurobiological mechanisms.MethodsThis study included three cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 722), the UK Biobank (UKB, N = 405,112), and the China Longitudinal Aging Study (CLAS, N = 240). Participants were classified into irritability-positive (+) and irritability-negative (-) groups based on assessment of irritability.We used Linear mixed-effects models to assess irritability-related cognitive trajectory, Cox regression to estimate cognitive decline, mediation analysis to test the effect of amyloid-β (Aβ) on the relationship between irritability and cognitive decline, and enrichment analysis to identify the underlying pathological mechanisms of irritability.ResultsIrritability was associated with increased cognitive decline in both ADNI (HR = 1.49, 95% CI: 1.12-1.98) and UKB (HR = 1.09, 95% CI: 1.04-1.15) cohorts, with baseline irritability linked to faster Mini-Mental State Examination decline (2.76 versus 1.88). Mediation analysis showed that cerebrospinal fluid (CSF) Aβ mediated 19-24% of irritability's effect on cognitive decline, while precuneus Aβ pathology mediated 30-41%. Imaging analysis revealed significant thinning of the left precuneus cortex in individuals with irritability. Proteomic analysis indicated underlying pathways involving enhanced energy metabolism and suppressed signal transduction, with modifiable factors (air pollution and physical inactivity) associated with irritability-related pathological proteins.ConclusionsOur findings indicate that irritability is significantly associated with cognitive decline. This association may be driven by mechanisms involving precuneus pathology, increased energy metabolism, and suppressed signal transduction, though these results warrant confirmation in future studies.},
}

@article {pmid42489522,
year = {2026},
author = {Denier-Fields, DN and Gangnon, RE and Rivera-Rivera, LA and Betthauser, TJ and Bendlin, BB and Johnson, SC and Engelman, CD},
title = {Better cardiovascular health, measured by Life's Simple 7, is associated with lower white matter hyperintensity burden and greater cerebral blood flow over time.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261467045},
doi = {10.1177/13872877261467045},
pmid = {42489522},
issn = {1875-8908},
abstract = {BackgroundLifestyle factors have been studied for dementia risk, but few studies have comprehensively assessed both Alzheimer's disease (AD) and cerebrovascular disease (CBVD) pathologies.ObjectiveOur research aims to determine the relationships between lifestyle and dementia pathologies.MethodsWe analyzed data from 1208 Wisconsin Registry for Alzheimer's Prevention (WRAP) participants. The cohort is enriched for participants with a family history of AD and a higher proportion of APOE ε4 carriers (n = 478); participants are primarily female (n = 827), non-Hispanic white (n = 1088), and highly educated (≥3 years professional or college education; n = 803), with an average baseline age of 64. Life's Simple Seven (LS7) scores were calculated from questionnaire data and clinical vitals. Brain health outcomes included CBVD biomarkers (white matter hyperintensities and arterial spin labeling [ASL] cerebral perfusion), AD biomarkers (amyloid Pittsburgh compound B index and tau standardized uptake value ratio Mayo meta-temporal composite), and cognitive outcomes (Preclinical Alzheimer Cognitive Composite Score 3 [PACC3], Delayed Recall, Immediate Learning, and Executive Function).ResultsHigher LS7 scores were significantly associated with lower white matter hyperintensity burden and higher ASL perfusion at the 6-8 year interval, with nominal associations observed at earlier time points and for global cognition (PACC3). No consistent associations were observed with amyloid or tau PET measures.ConclusionsThis study provides evidence that the beneficial effects of LS7 on cognition are primarily through cerebrovascular pathways rather than through AD pathology.},
}

@article {pmid42489523,
year = {2026},
author = {Gobbo, S and Romano, D},
title = {Reduced differentiation of personality in Alzheimer's disease-like dementia and associations between informant report of personality change and cognitive decline.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469839},
doi = {10.1177/13872877261469839},
pmid = {42489523},
issn = {1875-8908},
abstract = {BackgroundPersonality changes are documented in Alzheimer's disease (AD), but research has focused almost exclusively on how much traits change rather than how the underlying personality structure reorganizes. Recent evidence from healthy aging shows that personality traits can de-differentiate over time, suggesting a decline of coherence of traits with age. Whether such personality de-differentiation also occurs in neurodegeneration and how personality and cognitive changes relate remains unknown.ObjectiveThis study aimed to examine structural changes in personality traits in individuals with AD-like dementias, using the HEXACO personality model administered cross-sectionally to informants and to a control group of informants of healthy older adults, and explore dimensional changes in the relationship between reported changes in personality and cognition.Methods207 informants of persons with AD-like dementia and 201 informants of healthy older adults completed the Hexaco Adjective Scales, referring both to the present time and to perceived changes in personality, and a questionnaire (e-Cog) to assess cognitive changes.ResultsPrincipal component analysis revealed a simplified personality structure in persons with AD but not in healthy older adults, with Emotionality not emerging as an independent factor in persons with AD. Network analyses indicated significant links between personality trait changes and declines across cognitive domains that differed between the two groups.ConclusionsAD-like dementias are characterized by a reduced differentiation of personality structure paralleling the simplification of cognitive organization, with the strongest impact observed in the Emotionality domain. Personality changes also co-occur with perceived cognitive decline, underscoring the need to integrate personality assessment in evaluating dementia.},
}

@article {pmid42489525,
year = {2026},
author = {Hewan, P and Wearn, A and Hogeveen, J and Williams, K and Spreng, RN and Turner, GR and , },
title = {Cortical microstructural integrity predicts an exploitation bias in older adulthood.},
journal = {The journals of gerontology. Series B, Psychological sciences and social sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/geronb/gbag132},
pmid = {42489525},
issn = {1758-5368},
abstract = {OBJECTIVES: Prefrontal regions are implicated in explore-exploit decision-making during foraging. Older adults often show an exploitation bias, and this age period is also marked by deteriorating prefrontal myelination. To investigate whether these phenomena are linked, we examined whether lower magnetization transfer saturation (MTsat), a myelin-sensitive quantitative MRI (qMRI) measure, in these regions predicts greater exploitation bias during foraging, and whether cortical microstructure is a better predictor of bias than macrostructure (i.e., cortical thickness).

METHODS: Cognitively healthy older adults with familial risk of Alzheimer's disease (AD) (N=118, 60-88 years) completed a foraging task indexing explore-exploit decision-making. qMRI was used to derive MTsat values for the frontopolar cortex (FPC), medial orbitofrontal cortex (OFC), rostral middle frontal gyrus (rMFG), dorsal anterior cingulate cortex (dACC), as well as the locus coeruleus (LC), a core subcortical region strongly implicated in explore-exploit decision-making. Secondary analyses examined associations between available AD risk markers and foraging.

RESULTS: Lower MTsat in the FPC, OFC, rMFG, and LC was associated with an exploitation bias, with LC and FPC emerging as the strongest predictors. No relationship was observed for the dACC. MTsat remained a significant predictor of foraging after controlling for cortical thickness. Observed associations were largely unrelated to AD risk markers.

DISCUSSION: Individual differences in cortical microstructural integrity within a well-defined explore-exploit circuit are associated with an exploitative decision-making bias in older adults. These findings highlight the value of qMRI microstructural integrity markers, beyond standard macrostructural assays, in characterizing the neural correlates of exploitation biases in later life.},
}

@article {pmid42489527,
year = {2026},
author = {Streit, WJ and Kuhrt, H and Bechmann, I},
title = {Elevated ferritin expression in microglia and extracellular amyloid-β deposition are associated with reduced neurofibrillary degeneration in human isocortex, but not allocortex.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470454},
doi = {10.1177/13872877261470454},
pmid = {42489527},
issn = {1875-8908},
abstract = {BackgroundPrior work in preclinical late-onset Alzheimer's disease (LOAD) focused on neuritic plaque development suggested that intracellular ferritin expression in microglia and extracellular deposition of amyloid-β (Aβ) are innate neuroprotective mechanisms geared specifically towards limiting aging-dependent increases in intracerebral free iron which likely contribute to development of neurofibrillary degeneration (NFD).ObjectiveImprove understanding of LOAD pathogenesis.MethodsImmunohistochemical comparison of the extent of NFD with the intensity of ferritin expression and Aβ deposition in three brain regions, including temporal lobe (entorhinal cortex, hippocampus), frontal, and occipital cortex in 34 non-demented human subjects at Braak stages II-III.ResultsFerritin-positive microglia are present with similar quantity and intensity in the allo- and isocortices of every individual in the cohort. Extracellular Aβ deposition in the isocortex is observed before substantial NFD develops, but in the allocortex (temporal lobe) there are no Aβ deposits in 50% of subjects despite extensive NFD. Cytoskeletal lesions in the allocortex consist of atrophic grid cells, abundant pretangles, neuropil threads, neurofibrillary tangles, and neuritic plaques; isocortical sites show either no NFD at all or only minimal NFD presenting as solitary pretangles or tangles, neuropil threads, or droplet degeneration spheres from ferroptotic neurons. Presence of degenerating grid neurons in entorhinal cortex coincides with microglial apoptosis.ConclusionsNeuroprotection via ferritin expression and Aβ deposition is more effective in the isocortex than in allocortex. Findings support the hypothesis that degeneration or death of neuroprotective microglia promotes neuronal degeneration.},
}

@article {pmid42489531,
year = {2026},
author = {Farzeen, I and Nazir, MM and Jaan, Z and Ghaffar, W and Masood, A and Yasmeen, M and Ashraf, A and Różański, H},
title = {Biochemical modulators of synaptic plasticity: New horizons in Alzheimer's disease treatment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469864},
doi = {10.1177/13872877261469864},
pmid = {42489531},
issn = {1875-8908},
abstract = {Synaptic dysfunction is the earliest and most critical pathological feature of Alzheimer's disease (AD), directly contributing to cognitive decline. This review provides an integrative overview of the molecular and biochemical modulators governing synaptic plasticity and their disruption in AD. We discuss how the collective impairment of Aβ aggregation, tau pathology, calcium imbalance, oxidative stress, and neuroinflammation affects dendritic spine morphology and synaptic connectivity. Particular attention is given to neurotrophins such as brain-derived neurotrophic factor and TrkB signaling, hormonal influences, likewise glucocorticoids, estrogens, testosterone, endocannabinoid pathways, lipid and cholesterol regulators like ApoE and lipid rafts, and epigenetic mechanisms that modulate synaptic resilience. We further evaluate the therapeutic potential of pharmacological agents, including cholinesterase inhibitors, NMDA receptor modulators, and multi-target directed ligands alongside nutraceuticals such as resveratrol, curcumin, omega-3 fatty acids, Withania somnifera, and Bacopa monnieri. Emerging technologies, including iPSC-derived neuronal models, optogenetics, and advanced neuroimaging biomarkers like SV2A PET, cerebrospinal fluid/plasma neurogranin, are also highlighted for their role in elucidating and monitoring synaptic integrity. Ultimately, targeting the biochemical modulators of synaptic plasticity offers a promising avenue for AD therapy, especially through combinatorial and precision-medicine strategies aimed at restoring synaptic function and cognitive performance.},
}

@article {pmid42489532,
year = {2026},
author = {Shin, SH and Mo, Y and Hwang, HS and Lee, M and Lee, JJ and Kim, C and Choi, HJ},
title = {MRI-free amyloid PET quantification using a deep learning model and white matter reference.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470021},
doi = {10.1177/13872877261470021},
pmid = {42489532},
issn = {1875-8908},
abstract = {BackgroundAccurate quantification of standardized uptake value ratio (SUVR) in amyloid PET is essential for Alzheimer's disease (AD) diagnosis but typically requires MRI-based segmentation due to subtle uptake differences between gray and white matter.ObjectiveThis study aimed to develop and validate a 3-dimensional deep learning model capable of segmenting these tissues directly from PET images to enable MRI-free SUVR quantification for AD diagnosis.MethodsThis retrospective study included 385 participants who underwent brain amyloid PET and MRI. After excluding 12 data-corrupted cases, 373 subjects were divided into training (n = 318) and test (n = 55) sets. External validation used 625 PET/CT scans from the Alzheimer's Disease Neuroimaging Initiative. Model performance was assessed using Dice coefficients and intersection over union. PET-based SUVRs derived from model-generated masks were compared with MRI-based SUVRs using Spearman correlation, and their diagnostic utility was evaluated by group differences and receiver operating characteristic analysis.ResultsThe model achieved high Dice coefficients for grey matter (GM; 0.785 internal, 0.743 external) and white matter (WM; 0.838 internal, 0.803 external). PET/CT-based SUVR values strongly correlated with MRI references (Spearman's ρ ≥ 0.98, p < 0.001). PET/CT-derived SUVRGM and SUVRGM/WM predicted amyloid status (AUC 0.86 and 0.85, respectively) and cognitive impairment (AUC 0.78).ConclusionsDeep learning-based amyloid PET segmentation enables accurate MRI-free quantification of gray and white matter SUVRs. This approach simplifies clinical workflow while maintaining diagnostic performance comparable to MRI-based methods for AD diagnosis.},
}

@article {pmid42489536,
year = {2026},
author = {Costa, T and Sensi, SL and Høilund-Carlsen, PF and Robakis, NK and Vissel, B and Espay, AJ},
title = {Do anti-amyloid therapies demonstrate clinically meaningful benefit? A Bayesian reappraisal.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469870},
doi = {10.1177/13872877261469870},
pmid = {42489536},
issn = {1875-8908},
abstract = {BackgroundRecent anti-amyloid trials have been interpreted as evidence of clinical benefit in Alzheimer's disease, although their relevance remains debated.ObjectiveTo reinterpret pooled randomized evidence on anti-amyloid therapies within a Bayesian framework focused on benefit and harm.MethodsPooled estimates from a recent Cochrane review were reanalyzed using posterior probability estimation with clinically relevant thresholds.ResultsThe probability that treatment effects reached clinically meaningful thresholds was generally low, whereas the probability of substantial harm, particularly amyloid-related imaging abnormalities, was high.ConclusionsCurrent randomized evidence suggests that statistically significant anti-amyloid effects may not translate into clinically meaningful benefit.},
}

@article {pmid42489538,
year = {2026},
author = {Wang, YC and Liu, TT and Huang, LY and Tan, CC and Tan, L and Xu, W},
title = {The interplay between impaired kidney function and hypertension in dementia: A 13-year longitudinal study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261470293},
doi = {10.1177/13872877261470293},
pmid = {42489538},
issn = {1875-8908},
abstract = {BackgroundHypertension and kidney function impairment (KFI) are established risk factors for dementia and may reinforce each other. However, whether their coexistence confers excess dementia risk remains unclear.ObjectiveTo examine the multiplicative and additive interactions between hypertension and KFI in relation to incident dementia and explore potential biological pathways.MethodsWe included 218,858 dementia-free adults followed for a mean of 13.2 years. KFI was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m[2]. Cox proportional hazards models assessed independent associations and multiplicative interaction, while additive interaction was evaluated using the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Plasma proteomic data on 2911 proteins were available for 6127 participants.ResultsHypertension was associated with dementia risk (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.17-1.31; p < 0.001), whereas KFI was not (HR, 1.02; 95% CI, 0.94-1.11; p = 0.571). A significant multiplicative interaction was observed (p = 0.018). KFI was associated with dementia only among participants with hypertension (HR, 1.15; 95% CI, 1.01-1.29; p = 0.023). A positive additive interaction was also observed (RERI, 0.27; 95% CI, 0.05-0.49; AP, 0.17; 95% CI, 0.05-0.29; SI, 1.84; 95% CI, 1.11-3.07), although it was attenuated after full adjustment. Proteomic analyses implicated immune and inflammatory pathways.ConclusionsHypertension may modify the association between impaired kidney function and dementia risk. Their coexistence may identify individuals at higher risk, but further studies are needed to confirm these findings and clarify the underlying mechanisms.},
}

@article {pmid42489907,
year = {2026},
author = {Noroozian, M and Givian, H and Vafaee, MS},
title = {Chronic schizophrenia versus Alzheimer's disease: neuroimaging perspectives on the late-life course of schizophrenia.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42489907},
issn = {1435-1463},
abstract = {Schizophrenia (SCZ) is a chronic mental disorder that typically starts in early adulthood. It is characterised by structural brain abnormalities that occur early in the course of the disease, such as changes in the synapses and alterations in the brain white matter, which consequently progress to brain atrophy in several regions of the brain, as well as white matter lesions. On the other hand, epidemiological evidence indicates improved survival and increased life expectancy among patients with SCZ, largely due to advances in diagnosis and medication management, resulting in a growing number of individuals reaching older age. In addition, several studies have shown accelerated aging and an increased risk of cognitive decline in these patients. Consequently, the healthcare system faces a growing challenge: older adults with chronic SCZ who are at increased risk of dementia (particularly Alzheimer-type dementia). Notably, many individuals with chronic SCZ have several modifiable risk factors for dementia, including obesity, diabetes, elevated low-density lipoprotein cholesterol (LDL), metabolic syndrome, physical inactivity, smoking, and social isolation which may result from a combination of long-term antipsychotic medication, lifestyle factors, and medical comorbidities. These factors overlap substantially with established risk factors for Alzheimer's disease (AD) and may contribute to increased vulnerability to cognitive decline and dementia in later life. The clinical presentation of older adults with chronic SCZ who develop progressive cognitive and functional decline may closely resemble AD, owing to overlapping features such as memory impairment, social withdrawal, psychomotor slowing, and gait disturbances associated with vascular and metabolic comorbidities. Distinguishing these conditions represents a major diagnostic challenge for cognitive neurologists and psychogeriatricians. Therefore, this narrative review critically examines the differential and overlapping neuroimaging features of chronic SCZ and AD to facilitate more accurate clinical assessment and diagnosis in late life.},
}

@article {pmid42489967,
year = {2026},
author = {Søraas, A and Engvig, A and Alnæs, D and Karim, LN and Danilova, E and Istre, MS and Nygaard, S and Utgård, TR and Ceprnjic, S and Reiakvam, O and Edvardsen, E and Westlye, LT and Nygaard, AB and Dahl, JA and Nissen-Meyer, LSH and Ihle-Hansen, H and Holland, P},
title = {Interstitial fluid rejuvenation through young-donor plasma exchange in cognitively impaired patients: a pilot safety and feasibility study.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42489967},
issn = {2509-2723},
abstract = {Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer's disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient's blood plasma and replacing it with plasma from young and healthy donors has not been tested. Here, we have performed a pilot study to characterize the feasibility and safety of such a procedure, replacing between 16 and 26 L of patient blood plasma with young (ages 18-24) donor blood plasma for twelve patients who recently received a diagnosis of mild cognitive impairment with biomarker evidence of AD. The dose and time interval between plasma exchanges was tailored to maximize equilibration of donor plasma components into the interstitial fluid, with the aim of achieving what we term interstitial rejuvenation. We explored three permutations of a plasma exchange protocol with different treatment intensities and doses, each performed on three to five patients. We present data on safety, feasibility, patient burden, resource use of the treatments, preliminary measurements of clinical variables, and short-term cognitive trajectories in the patients. The procedures were feasible, and the adverse events observed were consistent with known risks of plasma exchange, supporting further investigation of treatment efficacy in a larger controlled trial. This safety and feasibility study was first registered 22 December 2023 at ClinicalTrials.gov and given the identifier NCT06234436.},
}

@article {pmid42489996,
year = {2026},
author = {Ahmed, HM and Al-Hussainy, AF and Arora, V and Rekha, MM and Kundlas, M and Chennakesavulu, K and Manu, M and Rizaev, J and Taher, SG and Alwan, M and Jawad, M and Mushtaq, H},
title = {Elevated CSF GAP-43 is associated with reduced cerebral glucose metabolism and cognitive impairment in individuals with mild cognitive impairment.},
journal = {Brain imaging and behavior},
volume = {20},
number = {4},
pages = {},
pmid = {42489996},
issn = {1931-7565},
mesh = {Humans ; *GAP-43 Protein/cerebrospinal fluid ; *Cognitive Dysfunction/cerebrospinal fluid/metabolism/diagnostic imaging ; *Glucose/metabolism ; Male ; Female ; Positron-Emission Tomography ; Alzheimer Disease/metabolism/cerebrospinal fluid/diagnostic imaging ; Aged ; Fluorodeoxyglucose F18 ; Biomarkers/cerebrospinal fluid ; *Brain/metabolism/diagnostic imaging ; Aged, 80 and over ; Neuropsychological Tests ; },
abstract = {Growth-associated protein 43 (GAP-43), a synaptic protein involved in neuronal plasticity, has emerged as a potential biomarker for Alzheimer's disease (AD) and mild cognitive impairment (MCI), with elevated levels linked to synaptic dysfunction. This dysfunction, in turn, has been associated with reduced cerebral glucose metabolism, which further exacerbates cognitive decline and accelerates disease progression. However, the link between CSF GAP-43 and cerebral glucose metabolism, measured by FDG-PET, remains less understood. This study aimed to investigate the relationship between CSF GAP-43 levels, cerebral glucose metabolism, and cognitive performance across different stages of cognitive impairment, specifically in individuals with AD (n = 83), MCI (n = 370), and cognitively normal (CN; n = 215). Cognitive function was assessed using the ADAS-Cog 13 scale, CSF GAP-43 levels were measured via ELISA, and cerebral glucose metabolism was analyzed with FDG-PET. The results showed that CSF GAP-43 levels were significantly elevated in the AD group compared to the CN and MCI groups (p < 0.001). In the MCI group, there was a modest but statistically significant negative association between CSF GAP-43 levels and cerebral glucose metabolism (β = -0.126, FDR p = 0.003), whereas this association was not significant in the CN (β = -0.031, FDR p = 0.612) or AD groups (β = 0.157, FDR p = 0.584). Mediation analysis, adjusted for age, sex, education, and APOE ε4 carrier status, showed that FDG-PET cerebral glucose metabolism partly and statistically mediated the association between CSF GAP-43 and cognitive performance only in the MCI group (β = 0.047, FDR-adjusted p = 0.009). These findings indicate that higher CSF GAP-43 was associated with lower cerebral glucose metabolism, which in turn was associated with worse cognitive performance in MCI. However, because of limitations, cross-sectional design, and modest magnitude of the effects, these results should be interpreted as statistical associations rather than evidence that CSF GAP-43 impairs glucose metabolism or cognition.},
}

Humans
*GAP-43 Protein/cerebrospinal fluid
*Cognitive Dysfunction/cerebrospinal fluid/metabolism/diagnostic imaging
*Glucose/metabolism
Male
Female
Positron-Emission Tomography
Alzheimer Disease/metabolism/cerebrospinal fluid/diagnostic imaging
Aged
Fluorodeoxyglucose F18
Biomarkers/cerebrospinal fluid
*Brain/metabolism/diagnostic imaging
Aged, 80 and over
Neuropsychological Tests

@article {pmid42490036,
year = {2026},
author = {Just, C and Seibert, K and Chan, C and Maldonado-Correa, C and Jones, D},
title = {Considerations in Alzheimer's Disease in Women.},
journal = {Current neurology and neuroscience reports},
volume = {26},
number = {1},
pages = {},
pmid = {42490036},
issn = {1534-6293},
mesh = {Humans ; *Alzheimer Disease/diagnosis/metabolism ; Female ; *Sex Characteristics ; Biomarkers ; tau Proteins/metabolism ; },
abstract = {PURPOSE OF REVIEW: To examine sex differences in Alzheimer's disease and cognition with a focus on hormonal transitions, biomarker trajectory, and implications for diagnosis and treatment.

RECENT FINDINGS: Women account for nearly two-thirds of individuals with Alzheimer's disease and demonstrate important biological and clinical differences compared with men. APOE ε4 confers greater risk in women, while menopause, depression, chronic stress, adverse pregnancy outcomes, and metabolic dysfunction may further increase vulnerability. Biomarker studies suggest that amyloid trajectories are broadly similar between sexes, but women exhibit earlier or greater tau accumulation once amyloid pathology is present. Women may maintain verbal memory performance longer than men despite underlying pathology, potentially delaying diagnosis. Emerging plasma biomarkers, particularly p-tau217, may improve early detection, monitoring, and treatment. Alzheimer's disease in women reflects a complex interaction between sex-specific biology, hormonal transitions, psychosocial factors, and neurodegenerative processes. Recognizing these differences has important implications for cognitive assessment, biomarker interpretation, diagnosis, and application of disease-modifying therapies.},
}

Humans
*Alzheimer Disease/diagnosis/metabolism
Female
*Sex Characteristics
Biomarkers
tau Proteins/metabolism

@article {pmid42490197,
year = {2026},
author = {Ko, E and Cho, H},
title = {Ethical Considerations of Artificial Intelligence in Dementia Research: A Review of Reviews.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnag158},
pmid = {42490197},
issn = {1758-5341},
abstract = {BACKGROUND AND OBJECTIVES: To examine the ethical considerations related to artificial intelligence technologies in dementia across diagnostic, management, and to synthesize these considerations using existing artificial intelligence and bioethical ethics principles.

RESEARCH DESIGN AND METHODS: The review of reviews synthesized evidence from published reviews addressing ethical considerations in published review-level evidence on ethical issues related to artificial intelligence for dementia and Alzheimer's disease. Findings were extracted and narratively synthesized. Ethical issues were mapped to the four UNESCO value domains and four traditional bioethical principles to provide an interpretive framework.

RESULTS: Eighteen reviews were included. Ethical concerns were related to algorithmic bias, limited diverse data, privacy, data security, data governance, fairness, and psychosocioeconomic and environmental well-being, and caregiving contexts. Based on UNESCO's four domains, six themes were identified: protection of human rights, technical trustworthiness, respect for human dignity, equity and access, governance, and environmental well-being. Ethical concerns prioritized the respect and protection of human rights and dignity, whereas environmental and ecosystem considerations were under focused. While many categories aligned with the traditional bioethical principles of autonomy, beneficence, non-maleficence, and justice, some concerns related to environmental well-being and data governance were difficult to classify within this framework.

DISCUSSION AND IMPLICATIONS: Our findings highlight the importance of embedding ethical principles in individual-level and system-level design implications to support the ethical and sustainable use of artificial intelligence in dementia care. This review will help healthcare professionals understand and address the ethical considerations in various dementia care settings where artificial intelligence is introduced or evaluated.},
}

@article {pmid42490359,
year = {2026},
author = {Lotfalinezhad, E and Freeman, S and Kearns, W and Chehrehgosha, M and Nadrian, H and Stokes, JE and Barati, F and Amirkhani-Ardeh, S and Mancheri, H and Jouybari, L and Genge, C},
title = {Navigating the Continuum: System-Level Requirements for High-Quality Dementia Care Transitions.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175261471717},
doi = {10.1177/15333175261471717},
pmid = {42490359},
issn = {1938-2731},
mesh = {Humans ; *Dementia/therapy ; *Patient-Centered Care/standards ; *Quality of Health Care/standards ; *Continuity of Patient Care/standards ; },
abstract = {The worldwide rise in dementia cases is creating significant pressures on healthcare systems, clinicians, and decision-makers. As dementia does not follow a single predictable pathway, individuals commonly move across different care settings as their needs evolve, requiring coordinated and integrated responses across the healthcare system rather than isolated efforts within single services. This perspective study explores service quality and underlying structural challenges throughout the dementia care pathway with a particular concentration on transitions between various stages. Key barriers to successful implementation include fragmented service delivery, short-term funding structures, weak coordination across care settings, staffing constraints, and challenges in staff retention. These challenges undermine care standards and result in avoidable emergency department and acute care utilization that contribute to increasing health systems expenditures. Strengthening integrated, person-centered, and transition-oriented care frameworks is critical to enhance outcomes and support sustainable health system responses to an increasing global impact of dementia.},
}

Humans
*Dementia/therapy
*Patient-Centered Care/standards
*Quality of Health Care/standards
*Continuity of Patient Care/standards

@article {pmid42490402,
year = {2026},
author = {Lu, X and Shen, X},
title = {On the Directionality of Predictor-Outcome Assignment When Modeling Polygenic Risk for Alzheimer's Disease Alongside Sleep Arousal Phenotypes.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag198},
pmid = {42490402},
issn = {1550-9109},
}

@article {pmid42490471,
year = {2026},
author = {Smith, JE},
title = {Alzheimer's trial results lend momentum to drugs targeting tau.},
journal = {Science (New York, N.Y.)},
volume = {393},
number = {6809},
pages = {343-344},
doi = {10.1126/science.aek8032},
pmid = {42490471},
issn = {1095-9203},
mesh = {*tau Proteins/metabolism/antagonists & inhibitors ; *Alzheimer Disease/drug therapy/metabolism ; Humans ; Indoles ; },
abstract = {First drug to lower the protein and slow cognitive decline created buzz despite puzzling data.},
}

*tau Proteins/metabolism/antagonists & inhibitors
*Alzheimer Disease/drug therapy/metabolism
Humans
Indoles

@article {pmid42490473,
year = {2026},
author = {Zhang, Y and Lu, X and Kunisky, AK and Alam, S and Tang, J and Zhang, R and Wang, S and Zhang, H and Baroudi, J and Ichcho, W and Jia, D and Ghorbanikalateh, S and Ghorbanikalateh, S and Wang, S and Bennett, DA and Mathys, H and Duan, Z and Ma, J},
title = {Single-cell multiomics connects 3D genome and transcriptome alterations in Alzheimer's disease.},
journal = {Science (New York, N.Y.)},
volume = {393},
number = {6809},
pages = {eadz1652},
doi = {10.1126/science.adz1652},
pmid = {42490473},
issn = {1095-9203},
mesh = {Humans ; *Alzheimer Disease/genetics/pathology ; *Chromatin/chemistry/metabolism/genetics/ultrastructure ; *Single-Cell Analysis ; *Transcriptome ; Multiomics ; Spatial Transcriptomics ; Brain/metabolism/pathology ; *Chromatin Assembly and Disassembly ; Gene Expression Regulation ; *Genome, Human ; Single-Cell Gene Expression Analysis ; },
abstract = {Alzheimer's disease (AD) disrupts brain function through cell type-specific transcriptomic and epigenomic alterations, yet the contribution of three-dimensional (3D) genome organization to AD remains poorly understood. We applied GAGE-seq (genome architecture and gene expression by sequencing) to jointly profile gene expression and 3D chromatin structure in single cells from postmortem brain tissue from AD patients and age-matched individuals without AD, revealing chromatin reorganization linked to cell type-specific dysregulation. Integrations with spatial transcriptomics and chromatin accessibility data uncovered altered niches reflecting genome compartment remodeling and regulatory element reorganization. Hicformer, a deep learning framework, showed that 3D genome features are essential for predicting disease-relevant, cell type-specific gene expression changes. Our results establish higher-order chromatin alterations as a component of AD-associated molecular pathology, providing a multiscale view of transcriptional regulation and 3D genome organization in neurodegeneration.},
}

Humans
*Alzheimer Disease/genetics/pathology
*Chromatin/chemistry/metabolism/genetics/ultrastructure
*Single-Cell Analysis
*Transcriptome
Multiomics
Spatial Transcriptomics
Brain/metabolism/pathology
*Chromatin Assembly and Disassembly
Gene Expression Regulation
*Genome, Human
Single-Cell Gene Expression Analysis

@article {pmid42490707,
year = {2026},
author = {Cossette-Lefebvre, M and Bergeron, N},
title = {[Cooccurrence of catatonia, delirium and dementia in an elderly woman: A case report].},
journal = {Sante mentale au Quebec},
volume = {51},
number = {1},
pages = {95-104},
pmid = {42490707},
issn = {1708-3923},
mesh = {Humans ; Female ; *Catatonia/complications/diagnosis ; *Dementia/complications/diagnosis ; *Delirium/complications/diagnosis ; Aged ; },
abstract = {Catatonia is a severe but underrecognized neuropsychiatric syndrome that is frequently misdiagnosed as delirium or dementia in older adults, resulting in delayed and potentially inappropriate treatment. A 79-year-old woman was admitted for rapid cognitive decline, significant weight loss, and social withdrawal. Initial evaluations suggested major depressive disorder or dementia. Neurological investigations were inconclusive. Following the initiation of psychotropic medication, psychiatric assessment revealed mutism, posturing, and marked psychomotor retardation, fulfilling DSM-5 criteria for catatonia. A lorazepam challenge test confirmed the diagnosis. Psychotropic medications were discontinued, and lorazepam was titrated to 2 mg 4 times daily, resulting in significant clinical improvement. Subsequent brain positron emission tomography (PET) imaging along with clinical evidence supported the presence of an underlying Alzheimer's disease. However, the emergence of superimposed delirium required gradual benzodiazepine tapering. Memantine was subsequently introduced, allowing lorazepam withdrawal and full symptomatic remission. The patient was discharged home. During outpatient follow-up, recurrence of partial symptoms prompted consideration of alternative therapeutic strategies. This case underscores the importance of recognizing catatonia in older adults presenting with cognitive impairment. It highlights the diagnostic and therapeutic challenges posed by the coexistence of catatonia, delirium, and neurodegenerative disease, and emphasizes the need for early identification and a multidisciplinary approach to optimize outcomes.},
}

Humans
Female
*Catatonia/complications/diagnosis
*Dementia/complications/diagnosis
*Delirium/complications/diagnosis
Aged

@article {pmid42490982,
year = {2026},
author = {Ramamurthy, B and Cho, A and Abdolmaleki, M and Fayez, N and Roby, D and Maynard, KB and Jefferson, AL and Bolton, C},
title = {Short-term psychological impacts of Alzheimer's disease risk disclosure based on blood-biomarker results.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70295},
doi = {10.1002/trc2.70295},
pmid = {42490982},
issn = {2352-8737},
abstract = {INTRODUCTION: Blood-based biomarkers (BBMs) of Alzheimer's disease (AD) provide important information about risk for dementia, but little is known about the psychological impact of sharing BBM results to participants with mild cognitive impairment (MCI). Most AD risk disclosure studies have been conducted in cognitively unimpaired individuals and have not used BBMs. This pilot randomized trial tests the hypothesis that disclosing AD risk based on BBMs is not associated with increased psychological harm compared to standard disclosure methods.

METHODS: Participants (n = 27, 73 ± 11 years) with MCI were enrolled and randomized to the intervention (n = 16) or control (n = 11) arm. Participants received a risk estimate based on their age, sex, and equivalent Mini-Mental State Examination score for both groups, with plasma phosphorylated tau 181 results included for the intervention group. Participants completed questionnaires assessing depression, anxiety, and hopelessness prior to disclosure and 2 weeks later. A repeated measures multivariate analysis of variance (MANOVA) was used to determine changes in psychological responses over the follow-up period with a time x group interaction term assessing group differences.

RESULTS: Participants in the intervention and control group were similar across baseline demographic and clinical factors (P values ≥ 0.23). Repeated measures MANOVA showed a significant reduction in psychological symptoms from baseline to 2-week follow-up (P = 0.006) in the combined sample. Follow-up univariate models showed the reduction was driven by a significant reduction in anxiety (mean ± standard deviation; baseline = 13.3 ± 7.7; follow-up = 9.8 ± 9.9; P = 0.02). Time x group interaction was non-significant (P = 0.31) indicating similar psychological responses across groups.

DISCUSSION: In this pilot study of participants with MCI, psychological response to learning risk of progression to dementia did not differ between those who received a risk estimate based on a BBM versus standard clinical information. Two weeks after disclosure, there was an overall decline in anxiety. These preliminary findings suggest that AD risk disclosure using BBMs is not associated with psychological distress.},
}

@article {pmid42490986,
year = {2026},
author = {Kim, GH and Yoon, HJ and Kim, EH and Kim, JY and Yeom, J and Kang, SY and Lee, B and Jeong, JH},
title = {Six-month real-world amyloid PET outcomes after lecanemab: Greater amyloid reduction at the MCI stage than in dementia.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70300},
doi = {10.1002/trc2.70300},
pmid = {42490986},
issn = {2352-8737},
abstract = {INTRODUCTION: Evidence from routine clinical practice regarding stage-dependent responses to lecanemab remains limited. We examined early amyloid positron emission tomography (PET) and clinical trajectories according to disease stage in a real-world cohort.

METHODS: Among 89 patients who received lecanemab, 50 individuals with baseline amyloid positivity and follow-up amyloid PET were included in the primary amyloid PET efficacy analysis. Amyloid burden was quantified using the Centiloid scale. Longitudinal Centiloid trajectories were analyzed using linear mixed-effects models including disease stage, time from baseline amyloid PET, and the disease stage × time interaction, with adjustment for cumulative dose exposure, age, sex, and apolipoprotein E (APOE) ε4 carrier status. Cognitive and functional outcomes were assessed using mixed-effects models.

RESULTS: Amyloid burden decreased substantially during follow-up. After adjustment for cumulative dose exposure, age, sex, and APOE ε4 carrier status, the disease stage × time interaction was significant (β = +1.62 Centiloid/month; 95% confidence interval, 0.80 to 2.43; p < 0.001), indicating a faster rate of Centiloid reduction in patients with mild cognitive impairment (MCI) than in those with dementia (estimated -2.34 vs. -0.72 Centiloid/month). Conversion to amyloid-negative status (full treatment-related amyloid clearance) occurred in 9 of 50 patients (18.0%) and was more frequent at the MCI stage (p = 0.022). Patients treated at the MCI stage also showed more favorable short-term cognitive and functional trajectories than those treated at the dementia stage.

DISCUSSION: In real-world clinical practice, lecanemab treatment was associated with substantial amyloid reduction, with faster amyloid clearance observed at the MCI stage. These findings support the potential value of earlier intervention with anti-amyloid therapy, although longer follow-up and controlled comparisons are needed to determine whether early biomarker changes translate into sustained clinical benefit.},
}

@article {pmid42490993,
year = {2026},
author = {Fong, A and Tabaie, A and Paylor, S and Tran, T and Iqbal, R and Ratwani, RM and Zafari, Z and Bangerter, LR and Brandt, NJ},
title = {Real-world pharmacovigilance for anti-Aβ therapies using a large language model.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70412},
doi = {10.1002/dad2.70412},
pmid = {42490993},
issn = {2352-8729},
abstract = {INTRODUCTION: Anti-amyloid beta (Aβ) therapies for early Alzheimer's disease require enhanced safety monitoring, yet adverse event (AE) documentation is diffuse across heterogeneous electronic health record documents. Large language models (LLMs) may improve scalable pharmacovigilance.

METHODS: We analyzed 20,123 clinical documents from 46 patients who received at least one dose of anti-Aβ therapy (June 24, 2024-July 30, 2025) at a large mid-Atlantic health-care system. We compared standard expert review versus an LLM-augmented workflow applied to the same documents. Expert reviewers annotated therapy-related AEs (e.g., amyloid-related imaging abnormalities with edema or hemorrhage, headache, syncope, hypersensitivity, gastrointestinal symptoms, infusion reactions). Discordant cases were adjudicated to establish a reference label.

RESULTS: After adjudication, 76% (35/46) patients had an AE. The LLM-augmented workflow achieved 100% sensitivity (positive predictive value [PPV] 89.7%) versus expert review 88.6% sensitivity (PPV 100%).

DISCUSSION: Findings provide preliminary indications that LLMs may serve as a pharmacovigilance signal detection tool, with a need for further validation and evaluation of clinical integration.},
}

@article {pmid42491022,
year = {2026},
author = {Yao, W and Lv, T and Zheng, W and Liu, Y and Shi, X and Zhang, Y and Song, Y and Bai, Y and Bai, F},
title = {Associations between neuronavigated rTMS-mediated functional connectome plasticity and neurotransmitter receptors in Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70294},
doi = {10.1002/trc2.70294},
pmid = {42491022},
issn = {2352-8737},
abstract = {INTRODUCTION: Cognitive improvement is mediated by repetitive transcranial magnetic stimulation (rTMS) in Alzheimer's disease (AD), and connectome gradient analysis has important potential to explore more comprehensive information for treatment efficacy. However, it remains unclear whether and how rTMS mediates connectome gradient reconstruction and its spatial neurotransmitter associations in subjects on the AD spectrum.

METHODS: A total of 84 subjects on the AD spectrum underwent 4 weeks of conventional neuronavigated rTMS targeting the left angular gyrus (20 Hz, 20 sessions over 4 weeks, 20 minutes per session), including 60 subjects with true stimulation and 24 with sham stimulation. This study identified functional connectome gradients and investigated their neuroplasticity between pre- and post-rTMS intervention. A support vector regression model was subsequently used to explore the cognitive prediction value of baseline measures. Finally, connectome‒neurotransmitter association analysis was used to investigate neurotransmitter profiles related to rTMS therapeutic efficacy.

RESULTS: These findings showed that rTMS treatment mainly mediated the decreased gradient values in the somatomotor regions and such baseline values of these regions showed preliminary predictive value for memory improvement after treatment (R [2]: 0.40-0.63, mean absolute error: 1.54-3.19, root mean square error: 1.98-3.94, p = 0.0002). Moreover, connectome-neurotransmitter association analysis suggested spatial associations between these gradient changes and normative metabotropic glutamate receptor 5 (mGluR5) and 5-hydroxytryptamine receptor 2A (5HT2a) receptor distributions.

DISCUSSION: rTMS mediates plasticity in high-order metric levels in the brain and is linked to the spatial distributions of specific neurotransmitter receptors in subjects on the AD spectrum.},
}

@article {pmid42491041,
year = {2026},
author = {Wei, Z and Bai, L and Liu, X and Zhou, Y and Zheng, L and Zhang, B and Wang, L and Zou, W},
title = {Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1820758},
doi = {10.3389/fnmol.2026.1820758},
pmid = {42491041},
issn = {1662-5099},
abstract = {Histone lactylation is an emerging epigenetic modification that covalently links the glycolytic metabolite lactate to histones, thereby establishing a direct link between cellular metabolic status and gene transcription programs. Recent studies have shown that this modification plays a key role in regulating cellular sensitivity to ferroptosis, forming a novel regulatory axis of "glycolysis-lactylation-ferroptosis." This article systematically reviews the biological functions of histone lactylation in the nervous system, with a focus on elucidating how it participates in the pathological processes of various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral stroke, and amyotrophic lateral sclerosis (ALS), by regulating the expression of ferroptosis-related genes. The article integrates the latest research on molecular mechanisms, explores the value of this regulatory axis as a potential biomarker for disease diagnosis and a therapeutic target, and provides an outlook on future research directions in this field.},
}

@article {pmid42491066,
year = {2026},
author = {Sah, RP and Cs, V and Jayaram, S and Yadav, AK and Pereira, P and Damodaran, J},
title = {Impact of Vitamin B12, Folate and Homocysteine in Modulating Cognitive Functions and the Brain's White Matter Hyperintensity in Alzheimer's Disease.},
journal = {Annals of neurosciences},
volume = {},
number = {},
pages = {09727531261457693},
doi = {10.1177/09727531261457693},
pmid = {42491066},
issn = {0972-7531},
abstract = {BACKGROUND: Deficiency of vitamin B12 and folate as surrogate factors attributed to cognitive deterioration among older adults with Alzheimer's disease (AD). Increased homocysteine levels >15 µmol/L (hyperhomocysteinaemia) due to insufficiency of vitamin B12 contribute to damage to the small blood vessels in the brain and aggravate the white matter lesion.

PURPOSE: The study aimed to determine the impact of B12, folic acid and homocysteine in modulating cognitive functions and white matter hyperintensity in AD.

METHODS: A case-control study of a total number of 82 patients (41 AD patients and 41 controls) was recruited. The cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA), and white matter hyperintensity was marked by magnetic resonance imaging studies. The levels of vitamin B12, folic acid and homocysteine in serum were also assessed.

RESULTS: The noticeable changes were observed in the cognitive scores and levels of B12, folic acid and homocysteine in AD and controls and found statistically significant (p < .001). Spearman's rank correlations revealed that cognitive functions (MoCA score) showed a direct correlation with B12 (ρ = 0.513, p < .001). Conversely, MoCA was moderately negatively correlated with homocysteine (ρ = -0.422, p < .001). Participants with B12 deficiency showed a significantly higher frequency of white-matter hyperintensities (WMH) (χ² = 4.654, p = .031; Fisher's exact p = .048).

CONCLUSION: Nutrient deficiencies, especially B12, have a disruptive impact on cognitive domains and WMH in AD, which could be considered as key indicators to identify the disease severity among older adults. Recommendations of vitamin B12 plus supplements might be connected to clinical and public health initiatives to halt the rate of progression of cognitive decline in AD.},
}

@article {pmid42491111,
year = {2026},
author = {Paranawithana, I and Doré, V and Bourgeat, P and Poon, A and Toh, HB and Thientunyakit, T and Kaewchur, T and Sutherland, A and Gillman, AG and Huang, K and Feizpour, A and Fripp, J and Villemagne, VL and Rowe, CC},
title = {Visual read performance of [18]F-Florbetapir and [18]F-NAV4694 Aβ PET compared against Centiloid reference standard in a paired cohort.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70426},
doi = {10.1002/dad2.70426},
pmid = {42491111},
issn = {2352-8729},
abstract = {INTRODUCTION: Visual assessment remains standard practice to rule out amyloid-β (Aβ) pathology. [18]F-NAV4694 (NAV) has high affinity for Aβ potentially detecting lower levels than other F-18 Aβ tracers.

METHODS: One hundred fifty participants in the AIBL study underwent both [18]F-Florbetapir (FBP) and NAV Aβ PET scans. PET scans were assessed by six nuclear medicine physicians against Centiloid (CL) quantification. An optimized reference region was utilized for FBP as it improved CL-visual read correlations. Inter-reader agreement of visual assessment was measured using Fleiss' Kappa.

RESULTS: Mean peak accuracy for visual read exceeded 95% for both NAV and FBP. However, peak accuracy for NAV visual reads was achieved at 14-15CL compared to 38-46CL for FBP. Higher inter-reader agreement was observed for NAV compared to FBP.

DISCUSSION: For mild to moderate elevation in Aβ, visual read of NAV is more sensitive and consistent than visual read of FBP by both experienced and novice readers.},
}

@article {pmid42491145,
year = {2026},
author = {Daniel, TD},
title = {Oscillatory dynamics as the coordination layer of the organism: waves, Markov blankets, and the virtual space of cognition.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1836602},
doi = {10.3389/fnins.2026.1836602},
pmid = {42491145},
issn = {1662-4548},
abstract = {Neural oscillations are not a mechanism that implements cognition. We present a new theoretical framework through a synthesis of relevant literature that has emerged in recent years: metabolic activity in the body, including but not limited to neural tissue, gives rise to an oscillatory pattern that contains information accessible to individual cells. The resulting dynamical structure allows cognitive activity to map the body in fine detail, to perceive its surroundings, or to extend into representations of objects and possibilities never encountered in the world. This array of possibilities is enabled by the coordination of the body's components, which imposes invariant structural regularities among them, in turn creating a moment-to-moment series of states shared across a distributed network of cells. Metabolic success involves ensuring adequate access to nutrition and waste removal for every cell and, when achieved, can give rise to a series of leaps manifested as increased access to complex higher-order affordances. The body's metabolic activity yields observable coordination; however, the mental actions themselves are inscrutable, existing only within a virtual space that unfolds in the interplay of the constituents of a particular body. Access to advanced functions is categorical; this virtual space expands during development and contracts in response to reduced metabolic sufficiency. Markov blankets formalize this asymmetry: brain-scanning technology clarifies the substrate, but no amount of information about the substrate provides direct access to cognitive activity. Frequency bands of oscillation correspond to spatial scales of inter-blanket communication, with cross-frequency coupling carrying information up and down the nested hierarchy. Several clinical conditions-ME/CFS, Long Coronavirus Disease (COVID), cancer-related cognitive impairment, Alzheimer's disease, and age-related decline-share a common upstream mechanism within this framework: cellular damage degrades the substrate, which contracts the space of accessible cognitive operations and produces the categorical incapacity patients report. The framework generates a testable prediction: aperiodic spectral flattening should temporally precede the loss of specific oscillatory peaks as the substrate degrades.},
}

@article {pmid42491578,
year = {2026},
author = {Xie, B and Liu, J and Hao, Y and Fu, X and Yang, S and Guo, C and Yang, Y},
title = {Peripheral inflammation impairs glymphatic function, contributing to neurodegeneration in Alzheimer's disease.},
journal = {iScience},
volume = {29},
number = {7},
pages = {116581},
doi = {10.1016/j.isci.2026.116581},
pmid = {42491578},
issn = {2589-0042},
abstract = {Alzheimer's disease (AD) is associated with systemic immune alterations and glymphatic dysfunction, both of which are linked to brain structural and network changes that contribute to cognitive decline. In 570 participants with AD, mild cognitive impairment, or normal cognition, we combined peripheral immune profiling with multimodal magnetic resonance imaging (MRI) to evaluate glymphatic function, brain structure, and network organization. AD was characterized by reduced analysis along the perivascular space index, enlarged choroid plexus (CP) volume, increased white matter free water, reduced lymphocyte count, and elevated neutrophil-to-lymphocyte ratio (NLR). Immune indices, including NLR, platelet-to-lymphocyte ratio, systemic immune-inflammation index, and lymphocyte count, were associated with cognition and glymphatic-related MRI measures. Mediation analyses indicated that NLR influenced cognition indirectly through CP volume and downstream brain structural and network features. These findings link peripheral immune imbalance to cognitive decline through glymphatic and brain network alterations, supporting biomarker development and mechanism-guided therapeutic strategies.},
}

@article {pmid42491583,
year = {2026},
author = {Luo, C and Wang, R and Yang, F and Qin, L and Ren, Y and Guo, M and Cai, H and Feng, S and Li, N and Gao, H and Tang, Y and Chen, Q},
title = {Nonlinear L-shaped association between composite dietary antioxidant index and risk of dementia: a prospective cohort study.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1839421},
doi = {10.3389/fpubh.2026.1839421},
pmid = {42491583},
issn = {2296-2565},
mesh = {Humans ; Male ; Prospective Studies ; *Antioxidants/administration & dosage ; Female ; *Diet/statistics & numerical data ; *Dementia/epidemiology ; United Kingdom/epidemiology ; Risk Factors ; Aged ; Proportional Hazards Models ; },
abstract = {OBJECTIVE: Dietary intake of antioxidants may decrease risk of dementia. However, the relationship between the composite dietary antioxidant index (CDAI) and dementia, has not yet been explored. This study investigated the relationship between CDAI and risk of dementia and to explore potential mediators of the relationship.

METHODS: Data were extracted from the prospective UK Biobank on 157,742 dementia-free participants, who were followed up for a median of 13.39 yr. Potential associations between CDAI at enrollment and subsequent development of all-cause dementia, Alzheimer's dementia or vascular dementia were assessed using Cox proportional hazards regression. Potential non-linear associations were explored using restricted cubic spline analysis. Exploratory analyses were performed to assess whether blood inflammatory markers and cortical/subcortical gray matter volumes accounted for part of the associations, using multivariable linear regression and mediation analyses.

RESULTS: During follow-up, 791 people developed Alzheimer's dementia, 322 developed vascular dementia, and 709 developed other types of dementia. Higher CDAI was significantly associated with lower risk of all-cause dementia and Alzheimer's dementia, and the association was stronger in women than in men (p for interaction < 0.05). The association was nonlinear and L-shaped (nonlinear p ≤ 0.001), with inflection points at 1.579 for all-cause dementia and 0.848 for Alzheimer's dementia. At CDAIs below these inflection points, each unit increase in CDAI was associated with 6.3% lower risk of all-cause dementia (HR 0.937, 95% CI 0.907-0.968, P < 0.001) and 6.5% lower risk of Alzheimer's dementia (HR 0.935, 95% CI 0.897-0.974, P = 0.001). Exploratory pathway analyses suggested that neutrophil and lymphocyte percentages modestly accounted for the association between CDAI and risk of all-cause dementia and Alzheimer's dementia.

CONCLUSIONS: CDAI may relate to risk of dementia in an L-shaped manner. Exploratory analyses suggested a possible role of systemic inflammation in this association.},
}

Humans
Male
Prospective Studies
*Antioxidants/administration & dosage
Female
*Diet/statistics & numerical data
*Dementia/epidemiology
United Kingdom/epidemiology
Risk Factors
Aged
Proportional Hazards Models

@article {pmid42491623,
year = {2026},
author = {Baker, S},
title = {Dr. David Perlmutter: New Steps to Targeting Brain Health and Alzheimer's Disease.},
journal = {Integrative medicine (Encinitas, Calif.)},
volume = {25},
number = {3},
pages = {38-43},
pmid = {42491623},
issn = {1546-993X},
}

@article {pmid42491893,
year = {2026},
author = {Munipalli, UMR and Annepu, V},
title = {A deep residual attention-Recurrent model for early and multi-stage Alzheimer's disease detection.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1798861},
doi = {10.3389/fnagi.2026.1798861},
pmid = {42491893},
issn = {1663-4365},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that requires accurate and early diagnosis. Deep learning methods have shown significant potential for automated MRI-based AD classification.

METHODS: A hybrid deep learning framework integrating ResNet152V2, Convolutional Block Attention Module (CBAM), and Bidirectional Gated Recurrent Unit (Bi-GRU) was developed for three-class classification of Normal Cognition (NC), Mild Cognitive Impairment (MCI), and Alzheimer's Disease (AD). The model was trained using 2,100 ADNI subjects and externally validated using 900 OASIS subjects.

RESULTS: The proposed framework achieved 94.5% classification accuracy with an AUC of 95.0% on the ADNI dataset and 92.8% accuracy on the OASIS dataset. Comparative analyses demonstrated improvements of 5.2-7.0% over baseline models. Ablation studies confirmed the contribution of CBAM and Bi-GRU to overall performance.

DISCUSSION: The integration of deep residual feature extraction, attention-based refinement, and sequential modeling effectively captures disease-related anatomical patterns. The results suggest that the proposed framework may support automated multi-stage Alzheimer's disease classification and provide a foundation for future computer-aided diagnostic systems.},
}

@article {pmid42492000,
year = {2026},
author = {de Oliveira, AM and Vanetti, CLR and Alencar, F and da Conceição, ASGG and Martinez, LD and Sant Ana, LCFG and Carvalho, CL and Mattar, GP and Leduc, V and Cecilio, APA and de Almeida, VN and da Silva, MFR and Gonçalves, OR and Varotto, BLR and Serelli, LDS and Teixeira, EPPB and Forlenza, OV},
title = {Adaptation of the Direct Assessment of Functional Status (DAFS):a new tool to assess functional changes in people with Down syndrome.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250415},
doi = {10.1590/1980-5764-DN-2025-0415},
pmid = {42492000},
issn = {1980-5764},
abstract = {UNLABELLED: Functional decline in activities of daily living (ADL) is considered a marker of ageing and Alzheimer's disease. However, there is a lack of performance-based instruments specifically designed to assess ADL in adults and older adults with Down syndrome.

OBJECTIVE: To describe the adaptation process of the Direct Assessment of Functional Status (DAFS) to assess the functional capacity of adults with Down syndrome.

METHODS: The Direct Assessment of Functional Status-Brazilian Version (DAFS-BR) was administered to 15 adults with Down syndrome (nine men and six women) who were divided into two diagnostic groups: stable cognition and suspected dementia or cognitive impairment. The process was conducted in two phases: phase one was characterized by an adaptation in the tasks. In phase two, (cultural and semantic) equivalences were verified, as well as structural aspects, including layout and instructions. This phase was essential for verifying the applicability and comprehensibility of newly adapted tasks.

RESULTS: The DAFS-BR was adapted for the time orientation, communication (telephone use), moneyhandling skills, and shopping skills domains, considering the target population.

CONCLUSION: The adaptation process of the DAFS-BR for people with Down syndrome was made considering linguistic, psychological, and cultural idiosyncrasies in the target population, with the input of experts with relevant experience in each domain. After psychometric studies, the Direct Assessment of Functional Status-Down Syndrome (DAFS-DS) could be considered the first ecological instrument for evaluating functional status in adults with Down syndrome in Brazil to enhance both clinical practice and research.},
}

@article {pmid42478649,
year = {2026},
author = {Sarkar, R and Banerjee, K and Das, S and Sadhukahn, I and Bose, B and Biswas, R and Pan, S and Adhikary, K and Maiti, R},
title = {Micronutrient-Assisted Biomaterial Strategies as Neuropharmacological Modulators of Neuroinflammation and Oxidative Stress in Neurodegenerative Diseases.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X485083260630050618},
pmid = {42478649},
issn = {1875-6190},
abstract = {Neurodegeneration results from the convergence of several molecular processes, including inflammation in the brain (i.e., neuroinflammation), elevated levels of free radicals that damage cells, mitochondrial dysfunction, and the inability to remove damaged proteins from the brain. Even though many agents provide neuroprotection in research models, their clinical use is limited because they cannot effectively cross the blood-brain barrier to reach the areas of the brain where they are needed. Limitations include the inability to cross the blood-brain barrier, poor bioavailability, rapid metabolism and clearance, non-specific targeting, efflux by transport proteins, toxicity, and low solubility and stability. The classification of micronutrients (e.g., vitamins, polyphenols, minerals), which are naturally present antioxidants and anti-inflammatory substances, plays a role in modulating the most important signaling pathways in the body, including those mediating the inflammatory response (i.e., NF-κB and NLRP3) and the process that causes glial cell death (i.e., JAK/STAT). Micronutrients have a significant drawback for therapeutic use because they are rapidly metabolized and cannot cross the blood-brain barrier. Developments in synthetic biomaterials and nanotechnology offer a potential avenue for addressing the challenges of delivering micronutrients to the brain by targeting them to specific areas and releasing them over a sustained period. This study presents current information on the mechanisms by which micronutrients modulate molecular pathways and their potential application in emerging biomaterials to develop a new class of neuroprotective therapeutic agents that may ultimately be used to treat patients with degenerative diseases (e.g., Alzheimer's, Parkinson's, and Huntington's). Additionally, clinical challenges are addressed to translate these products from the laboratory to the clinic. The idea presented in this review connects molecular neuromodulation via micronutrients and bioactive nutraceuticals with a new strategy for pharmacological delivery using biomaterials. Instead of considering nutrition and those biomaterials as separate therapeutic areas, an integrated mechanistic model is presented that shows how micronutrients can act as endogenous pathway regulators and how biomaterials can enhance pharmacokinetics and targeting.},
}

@article {pmid42478671,
year = {2026},
author = {Sato, K and Niimi, Y and Ihara, R and Iwata, A and Iwatsubo, T},
title = {Projected lecanemab wastage from vial discard: Simulation based on Japanese interim post-marketing surveillance summary statistics.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469872},
doi = {10.1177/13872877261469872},
pmid = {42478671},
issn = {1875-8908},
abstract = {Lecanemab is dosed by body weight but supplied as fixed-size single-dose vials, which can leave unavoidable leftover drug after preparation. Using published summary statistics from the Japanese lecanemab post-marketing surveillance on body weight, we fitted a body-weight distribution and ran Monte Carlo simulations. Uncertainty was quantified by a parametric bootstrap. With current 200/500-mg vials, mean waste rate was 8.60%. A strategy with 200/250-mg vials reduced waste to 6.30%, and adding a 75-mg vial (≤4 vials/infusion) to 3.67%. At 10,000 person-years, annual waste cost was ∼¥2.36 billion under assumed pricing. Vial-size and dispensing optimization may help reduce avoidable waste.},
}

@article {pmid42478899,
year = {2026},
author = {Zhang, N and Chen, W and Wang, M},
title = {The liver-brain axis: A multidimensional regulatory network implicated in Alzheimer's disease pathogenesis and clinical implications.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70262},
pmid = {42478899},
issn = {2576-2095},
support = {Seed Program (YYZZ202409)//Capital Medical University Affiliated Beijing Friendship Hospital/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition. The liver-brain axis underscores the central role of the liver in modulating cognitive function through multidimensional regulatory mechanisms. As a core metabolic and detoxification organ, the liver also helps maintain cerebral homeostasis via pathways including the urea cycle, antioxidant systems, ketone body metabolism, and bile acid regulation. Dysfunction of these processes may lead to ammonia accumulation, exacerbated oxidative stress, and Aβ clearance, thereby accelerating the pathological progression of AD. Liver-derived factors such as apolipoprotein E (APOE), C-reactive protein (CRP), fibroblast growth factor 21 (FGF21), and insulin-like growth factor 1 (IGF-1) significantly increase the risk of AD through dual mechanisms-inhibiting Aβ clearance and activating neuroinflammation, thereby directly affecting cognitive function via modulation of inflammation, metabolism, and blood-brain barrier (BBB) integrity. Neural interfaces formed by the hypothalamic-pituitary-target gland axis and the vagus nerve enable communication from the liver to the brain, with emerging evidence also supporting a reverse influence from the brain to the liver. Emerging technologies such as molecular tracing and nanocarriers provide new tools for deciphering dynamic interactions within the liver-brain axis. Liver-targeted metabolic interventions show potential for reversing cognitive impairment. Unlike previous reviews that mainly focused on single pathways, this review conceptualizes the liver-brain axis as a multidimensional regulatory network in AD. By clearly linking network nodes to potential therapeutic interventions, it provides us with a novel framework that not only describes the various mechanisms but also focuses on identifying actionable targets for disease prevention and treatment.},
}

@article {pmid42479092,
year = {2026},
author = {Goswami, A and Lagad, RR and Rafi, S},
title = {Decoding neuronal gene expression: integrative insights from omics and AI.},
journal = {Brain informatics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40708-026-00323-z},
pmid = {42479092},
issn = {2198-4018},
abstract = {Neuronal functional diversity and pathological vulnerability are governed by multi-layered regulatory programs. While high-throughput omics and neuroimaging provide high-resolution snapshots of these programs, bridging the gap between molecular dynamics and macro-scale brain architecture remains a significant informatics challenge. This review synthesizes the evolution of computational frameworks in neuro-omics-transitioning from descriptive co-expression modules to causal graph neural networks and cross-scale foundation models. We evaluate these methodologies within the context of Alzheimer's disease, schizophrenia, and epilepsy, identifying critical bottlenecks in data harmonization, spatial alignment, and causal interpretability.},
}

@article {pmid42479178,
year = {2026},
author = {Agrawal, S and Wagner, M and Leurgans, SE and Agarwal, P and van der Weerd, L and Bennett, DA and Bush, AI and Ayton, S and Schneider, JA},
title = {Cerebral amyloid angiopathy, brain iron concentrations, and cognitive decline in older people.},
journal = {Acta neuropathologica},
volume = {152},
number = {1},
pages = {},
pmid = {42479178},
issn = {1432-0533},
mesh = {Humans ; *Cerebral Amyloid Angiopathy/pathology/metabolism/complications/psychology ; Female ; *Iron/metabolism ; Aged, 80 and over ; *Brain/pathology/metabolism ; *Cognitive Dysfunction/pathology/metabolism ; Male ; Aged ; Aging/pathology ; Longitudinal Studies ; },
abstract = {Cerebral amyloid angiopathy (CAA) is a common brain pathology in older people and has been recently recognized as a major risk factor for amyloid-related imaging abnormalities during anti-amyloid antibody therapy. CAA pathophysiology may involve iron released from ruptured vessels, but the association between postmortem CAA and brain iron is unclear. This study investigates the association between CAA and brain iron and whether elevated iron modifies the association between CAA and cognitive decline. We studied 626 Rush Memory and Aging Project decedents (mean age at death = 90 [SD = 6.1] years, 70% women) who completed baseline and longitudinal cognitive assessments and underwent detailed neuropathologic evaluation for CAA, Alzheimer's disease neuropathologic changes (ADNC), and other brain pathologies. Brain iron content was assessed from the inferior temporal cortex using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Linear regression and mixed-effects models were used for analysis. CAA was common: 266 (42%) had mild, 153 (24%) had moderate, and 75 (12%) had severe CAA. In analyses adjusted for demographics, intermediate/high ADNC, and other pathologies, the presence and severity of CAA were associated with elevated cortical brain iron (Est = 0.033, SE = 0.011, p = 0.002; Est = 0.017, SE = 0.004, p < 0.001, respectively). When examining associations with nonlinear cognitive change before death (mean follow-up = 7.7 [SD = 3.9] years), both CAA and elevated iron were independently associated with faster annual rates of decline in global cognition and semantic memory (all p < 0.04). Elevated iron was also associated with faster declines in episodic and working memory and perceptual speed (all p < 0.02). When exploring whether brain iron modulates the association of CAA with cognitive decline, we found that CAA had steeper decline in perceptual speed when elevated iron was present compared to when low iron was present (p = 0.03). Together, these findings suggest that brain iron may contribute to the clinical impact of CAA in older age.},
}

Humans
*Cerebral Amyloid Angiopathy/pathology/metabolism/complications/psychology
Female
*Iron/metabolism
Aged, 80 and over
*Brain/pathology/metabolism
*Cognitive Dysfunction/pathology/metabolism
Male
Aged
Aging/pathology
Longitudinal Studies

@article {pmid42479245,
year = {2026},
author = {An, X and Wu, D and Wang, Y and Ren, Z and Yu, W},
title = {Seipin modulates Alzheimer's disease pathogenesis by regulating ferroptosis through a glycine-mediated metabolic pathway.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42479245},
issn = {1573-7365},
support = {82160225//the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Alzheimer Disease/metabolism/genetics/pathology ; *Ferroptosis/physiology ; *GTP-Binding Protein gamma Subunits/metabolism/genetics ; *Glycine/metabolism ; Mice ; Mice, Transgenic ; Microglia/metabolism ; *Metabolic Networks and Pathways/physiology ; *Heterotrimeric GTP-Binding Proteins/metabolism/genetics ; Humans ; Hippocampus/metabolism ; },
abstract = {Alzheimer's disease (AD) remains an incurable neurodegenerative disorder with an elusive pathogenesis, where emerging evidence implicates metabolic dysregulation and ferroptosis in neuronal loss. Although the BSCL2 gene, which encodes Seipin, is crucial for lipid metabolism, its specific role in the progression of AD remains undefined. This study employed Mendelian randomization (MR) analysis, in vivo APP/PS1 mouse models, and in vitro BV2 microglial assays to elucidate the mechanistic axis linking BSCL2, metabolites, and ferroptosis in AD. MR analysis demonstrated a causal relationship between genetically predicted elevated BSCL2 expression and an increased risk of AD, partially mediated by glycine. Supporting these genetic findings, stereotactic knockdown of Seipin in the hippocampus of APP/PS1 mice significantly ameliorated cognitive deficits without inducing systemic metabolic toxicity. Mechanistically, Seipin deficiency reduced ferroptosis in both AD mouse brains and Aβ-stimulated microglia, as evidenced by the upregulation of anti-ferroptotic markers (GPX4, Nrf2, HO-1) and the suppression of pro-ferroptotic effectors (ACSL4, NCOA4). Moreover, glycine supplementation partially ameliorated the aggravated ferroptotic phenotype caused by Seipin overexpression, indicating a functional feedback mechanism in which glycine facilitates glutathione synthesis to mitigate Seipin-induced lipid peroxidation. These findings collectively identify Seipin as a novel regulator of ferroptosis in the pathogenesis of AD and underscore the potential of the BSCL2-glycine-ferroptosis axis as a therapeutic target. Future research should aim to elucidate the specific molecular interactions between Seipin and the iron-handling machinery and to validate glycine-based interventions in clinical settings as a means to prevent neurodegeneration.},
}

Animals
*Alzheimer Disease/metabolism/genetics/pathology
*Ferroptosis/physiology
*GTP-Binding Protein gamma Subunits/metabolism/genetics
*Glycine/metabolism
Mice
Mice, Transgenic
Microglia/metabolism
*Metabolic Networks and Pathways/physiology
*Heterotrimeric GTP-Binding Proteins/metabolism/genetics
Humans
Hippocampus/metabolism

@article {pmid42479414,
year = {2026},
author = {Cai, Y and Chen, Y and Huang, G and Ren, M and Chai, Y and Gai, C and Huang, X and Yan, T},
title = {Integrated bioinformatics and experimental analysis identify apoptosis- and pyroptosis-related hub genes as candidate diagnostic biomarkers in Alzheimer's disease.},
journal = {Journal of applied genetics},
volume = {},
number = {},
pages = {},
pmid = {42479414},
issn = {2190-3883},
support = {KYCX24_2248//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; },
abstract = {Apoptosis and pyroptosis-mediated neuronal death represent major pathogenic mechanisms underlying Alzheimer's disease (AD). Given the potential crosstalk between these two forms of cell death, investigation of a single death pathway may be insufficient to identify robust diagnostic biomarkers for AD. Therefore, this study aimed to explore hub genes involved in both apoptosis and pyroptosis as potential diagnostic biomarkers for AD. First, 23 common cell death-related genes (CDRGs) were identified through bioinformatic analysis. Functional enrichment analyses using GO, KEGG, and GeneMANIA revealed significant associations between AD and biological processes including apoptosis, pyroptosis, and neuronal death. Subsequently, machine learning algorithms combined with ROC curve analysis identified CASP3, IL1B, NLRP3, and PYCARD as candidate biomarkers with potential diagnostic and therapeutic implications for AD. These findings were further validated by the in vitro experiments, which confirmed that the expression levels of these four biomarkers were consistent with the predicted results. Additionally, in patients with AD, CASP3, IL1B, NLRP3, and PYCARD were negatively correlated with macrophages. Collectively, these results suggest that the identified biomarkers may co-regulate apoptosis and pyroptosis through macrophages, thereby contributing to the pathogenesis of AD.},
}

@article {pmid42479540,
year = {2026},
author = {Zhang, J and Yu, P and Xu, M and Liang, F and Chen, Y and Dong, Y and Zhang, Y and Yu, S and Hua, F and Otu, HH and Libermann, TA and Inouye, SK and Marcantonio, ER and Yang, G and Xie, Z},
title = {Anesthesia and surgery induce sex-dependent Tau phosphorylation and behavior changes in aged mice.},
journal = {Anesthesiology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ALN.0000000000006261},
pmid = {42479540},
issn = {1528-1175},
abstract = {BACKGROUND: Preoperative blood Tau phosphorylated at threonine 217 (Tau-PT217), a newly identified blood biomarker of Alzheimer's disease, is associated with postoperative delirium in patients. Anesthesia/surgery is also associated with postoperative increased blood Tau-PT217 amounts in patients. Moreover, in female aged mice, anesthesia/surgery increases Tau-PT217 in lungs, blood and brain tissues, leading to behavioral changes. However, whether these effects are sex-dependent remain largely undetermined.

METHODS: Eighteen-month-old female and male mice (C57BL/6J) underwent abdominal surgery under general anesthesia (1.4% isoflurane and 40% oxygen). Levels of Tau-PT217, inflammatory markers, and GSK3β activity were measured in lungs, blood, and brain tissues of aged mice using nanoneedle technology, Western blot, immunohistochemistry, RT-PCR and others. Postoperative delirium-like behavior was assessed using a battery of behavioral tests (buried food, open filed and Y maze). To explore causality, we performed orchiectomy and administered androgen receptor antagonist enzalutamide in aged male mice. Finally, testosterone was delivered via inhalation to aged female mice.

RESULTS: Anesthesia/surgery increased the amounts of Tau-PT217 in lungs (2.29±0.16 fold versus 1.15±0.71 fold, P<0.01), blood, and brain tissues of aged female, but not male, mice compared to control condition, leading to postoperative delirium-like behavior, as evidenced by increases in the composite Z score (3.74±1.46 versus 0.60±1.17, P<0.01), in the aged female, but not male, mice. Anesthesia/surgery elevated inflammatory markers and GSK3β activity in aged female mice, which exhibited lower baseline testosterone levels and androgen receptor expression in lungs compared to males. Both orchiectomy and enzalutamide treatment in male mice reduced testosterone levels and androgen receptor expression, leading to elevation of Tau-PT217 amounts and behavior changes following anesthesia/surgery. Conversely, testosterone inhalation in aged female mice mitigated the anesthesia/surgery-induced elevation of Tau-PT217 amounts and behavior changes.

CONCLUSIONS: Testosterone and androgen receptor signaling may contribute to the sex-dependent differences in Tau phosphorylation and postoperative behavior changes in aged mice.},
}

@article {pmid42479638,
year = {2026},
author = {Qin, R and Caiqi, L and Qingchun, Q and Xu, W and Lai, X and Chen, L},
title = {The burden of neurological diseases in East Asia: an analysis for the Global Burden of Disease Study 2023.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-25},
doi = {10.1159/000553093},
pmid = {42479638},
issn = {1423-0208},
abstract = {Background and Objectives Neurologic disorders represent a growing global health burden. According to the Global Burden of Disease Study 2023, they remain a major cause of morbidity and mortality worldwide. However, a comprehensive assessment specifically focused on East Asia has been lacking. This study investigates data from the GBD 1990-2023 study to provide detailed and updated insights into the burden of neurologic disorders in East Asia. Methods We analyzed the 1990-2023 burden of thirteen neurologic disorders in East Asia (e.g., stroke, dementia, epilepsy, migraine) using incidence, prevalence, deaths, and DALYs, stratified by sex, age, year, and location. Joinpoint regression assessed temporal trends and annual changes in age-standardized rates. Results In 2023, the neurologic disorders with the highest absolute DALYs in East Asia were stroke (44.42 million, 95% UI 39.17-49.56), Alzheimer's disease and other dementias (12.02 million, 95% UI 5.87-23.28), and migraine (6.80 million, 95% UI 4.56-9.33). Stroke was the leading cause of neurologic deaths (2.13 million, 95% UI 1.81-2.42), followed by Alzheimer's disease and other dementias (0.61 million, 95% UI 0.15-1.44) and Parkinson's disease (0.03 million, 95% UI 0.03-0.04 million). From 1990 to 2023, the overall Age-standardized DALY rates (ASDR) for neurologic disorders showed a slight decline (EAPC = -0.05; 95% CI: -0.1 to -0.01). However, both the absolute number of DALYs and the prevalence of neurological disorders demonstrated a steady increase, driven primarily by population growth and aging. This divergence between declining age-specific risk and rising absolute burden poses a mounting challenge for healthcare systems in the region. Substantial regional variation was observed in age-standardized rates across East Asia. Joinpoint regression analysis further revealed declining trends in the ASDR, ASIR, and ASPR for stroke, whereas Alzheimer's disease and other dementias showed significant increases across all three metrics. Migraine exhibited increases in ASDR, ASIR, and ASPR. Discussion This study provides the first comprehensive analysis of the burden of neurological disorders in East Asia from 1990 to 2023, revealing an urgent need for targeted public health strategies to address the growing challenge of neurological disorders.},
}

@article {pmid42479667,
year = {2026},
author = {Liang, C and Pearlson, G and Bustillo, J and Kochunov, P and Chen, J and Zhang, X and Jiang, R and Hutchison, KE and Sui, J and Fu, Z and Yang, X and Du, Y and Zhang, D and Qi, S and Calhoun, VD},
title = {Brain aging patterns among nine neurological disorders: A case-control study.},
journal = {PLoS medicine},
volume = {23},
number = {7},
pages = {e1004860},
pmid = {42479667},
issn = {1549-1676},
mesh = {Humans ; *Brain/diagnostic imaging/pathology ; Female ; *Aging/pathology ; Case-Control Studies ; Magnetic Resonance Imaging ; Male ; *Nervous System Diseases/diagnostic imaging/pathology/genetics ; Adult ; Middle Aged ; Neuroimaging ; Young Adult ; },
abstract = {BACKGROUND: The difference between neuroimaging-predicted brain age and chronological age, the predicted age difference (PAD), has been studied as a potential biomarker reflecting individual brain health. Although previous large-scale studies have shown that brain age deviations occur across multiple disorders, cross-disorder comparisons of PAD within a unified framework, together with identification of the neuroimaging features associated with these differences and their related gene expression profiles, remain limited. Our aims are to systematically compare brain aging across multiple common brain disorders and explore the brain patterns and biological processes underlying these differences.

METHODS AND FINDINGS: In this study, structural MRI data from 45,900 healthy controls (HCs) and 2,698 patients with developmental disorders (attention-deficit/hyperactivity disorder [ADHD] and autism spectrum disorder [ASD]), addiction (alcohol use disorder [AUD], tobacco use disorder [TUD], and AUD&TUD-A&TUD), dementia (Alzheimer's disease [AD], and mild cognitive impairment [MCI]) or other psychiatric disorders (schizophrenia [SZ], bipolar disorder [BP], and major depressive disorder [MDD]), were collected to generate PAD, along with transcriptome data. Then, we calculated the PAD difference between patient and HC as Cohen's d effect sizes, derived from a linear model that accounted for age, age2, sex, and site, and further identified the interpretable brain patterns associated with the PAD difference for each diagnostic group. Finally, enrichment analyses was conducted to identify the biological function of genes relatively over- or underexpressed in association with these patterns. Results showed that while PAD was consistently greater across disorders, different brain disorders showed different degrees of abnormality, the highest effects in dementia (AD: d = 0.97, 95% confidence interval (CI) [0.82,1.13]; p < 0.001 and MCI: d = 0.45, 95% CI [0.34,0.56]; p < 0.001), followed by addiction (A&TUD: d = 0.84, 95% CI [0.44,1.23]; p < 0.001, TUD: d = 0.72, 95% CI [0.49,0.96]; p < 0.001, and AUD d = 0.62, 95% CI [0.39,0.84]; p < 0.001) and psychiatric disorders (SZ: d = 0.53, 95% CI [0.30,0.76]; p < 0.001, BP: d = 0.46, 95% CI [0.22,0.69]; p < 0.001 and MDD: d = 0.28, 95% CI [0.11,0.46]; p < 0.001), but not different from expected in developmental disorders (ASD: d = 0.06, 95% CI [-0.04,0.16]; p = 0.36) and ADHD: d = 0.01, 95% CI [-0.14,0.15]; p = 0.98). Furthermore, higher PAD values in patient groups were linked to specific spatial brain patterns, including the frontotemporal network in psychiatric disorders, default mode network-salience network-putamen-thalamus in addiction and fronto-occipital network in dementia. Prefrontal cortex involvement was common across disorders, and disorder-specific brain patterns associated genes were enriched in different biological processes. A limitation of our study is that psychiatric disorders and addiction have high comorbidity, and these potential confounders were not considered.

CONCLUSIONS: In summary, the different brain aging patterns, each based around specific underlying circuits, may serve as neuroimaging biomarkers for understanding the neural aging mechanisms in commonly occurring brain disorders. Future studies should test whether these disorder-specific brain aging patterns can serve as useful biomarkers to guide critical clinical decision-making.},
}

Humans
*Brain/diagnostic imaging/pathology
Female
*Aging/pathology
Case-Control Studies
Magnetic Resonance Imaging
Male
*Nervous System Diseases/diagnostic imaging/pathology/genetics
Adult
Middle Aged
Neuroimaging
Young Adult

@article {pmid42479708,
year = {2026},
author = {Lee, Y and Kim, S and Kim, S and Kang, Y and , },
title = {Feature integration of [18F]FDG PET brain imaging using deep learning for sensitive cognitive decline detection.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0341995},
pmid = {42479708},
issn = {1932-6203},
mesh = {Humans ; *Positron-Emission Tomography/methods ; *Fluorodeoxyglucose F18 ; *Deep Learning ; *Brain/diagnostic imaging ; Convolutional Neural Networks ; *Cognitive Dysfunction/diagnostic imaging ; Female ; Male ; Aged ; Alzheimer Disease/diagnostic imaging ; },
abstract = {BACKGROUND: Distinguishing individuals with cognitive decline (CD), including early Alzheimer's disease, from cognitively normal (CN) individuals is essential for improving diagnostic accuracy and enabling timely intervention. Positron emission tomography (PET) captures metabolic brain alterations associated with CD, but its broader application is often limited by cost and radiation exposure. To enhance the clinical utility of PET while addressing data limitations, we propose a data-efficient framework that integrates complementary multi-scale PET representations at voxel-level and region-level.

METHODS: Voxel-level features were extracted using convolutional neural networks (CNN) or principal component analysis networks (PCANet) from [¹⁸F]FDG PET imaging. Region-level features were derived from standardized uptake value ratio measurements across predefined brain regions and processed using a deep neural network (DNN). These voxel- and region-level information are integrated through direct concatenation. For the final prediction, different machine learning models and ensemble technique were applied. The models were trained and validated using 5-fold cross-validation on PET scans from 252 participants in the Alzheimer's Disease Neuroimaging Initiative, comprising 118 CN and 134 CD subjects. Additional correlation analysis and disease classification comparison with the Mini-Mental State Examination (MMSE) were also performed.

RESULTS: In 5-fold cross-validation, CNN, PCANet, and DNN models achieved classification accuracies of 0.69 ± 0.04, 0.69 ± 0.06, and 0.82 ± 0.06, respectively. The integrated DNN-CNN model using direct concatenation yielded the highest accuracy (0.87 ± 0.05), with a 6.33% improvement in accuracy and reduced standard deviation relative to the DNN-only model. Overall, there were an increase of 14.22% in Recall (0.77 to 0.88) and an increase of 7.92% in F1-Score (0.82 to 0.88). Moreover, the predicted probability of CD showed a significant correlation with MMSE scores, and the model achieved higher accuracy, recall, and F1-score than MMSE-based classification.

CONCLUSION: Combining complementary voxel-level and region-level PET representations with deep learning improved classification performance over single-representation models, particularly by enhancing sensitivity to cognitive decline. These findings support the potential utility of multi-scale FDG-PET representations for machine learning-based cognitive decline detection.},
}

Humans
*Positron-Emission Tomography/methods
*Fluorodeoxyglucose F18
*Deep Learning
*Brain/diagnostic imaging
Convolutional Neural Networks
*Cognitive Dysfunction/diagnostic imaging
Female
Male
Aged
Alzheimer Disease/diagnostic imaging

@article {pmid42479714,
year = {2026},
author = {Buard, G and Verny, M},
title = {[Focus on limbic-predominant age-related TDP-43 encephalopathy (LATE)].},
journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement},
volume = {24},
number = {3},
pages = {0},
doi = {10.1684/pnv.2026.1294},
pmid = {42479714},
issn = {2115-7863},
abstract = {In 2019, an international working group described a new clinicopathological entity: limbic-predominant age-related TDP-43 encephalopathy (LATE). Neuropathologically, LATE is characterized by the abnormal accumulation of TDP-43 protein in limbic structures, particularly the hippocampus and parahippocampal regions. Clinically, LATE presents as a slowly progressive, isolated mesiotemporal amnestic syndrome, typically affecting individuals aged over 75 years. Brain MRI usually reveals marked hippocampal atrophy, while FDG-PET may demonstrate medial temporal hypometabolism. A diagnosis of probable LATE requires the exclusion of underlying amyloid pathology, although concomitant Alzheimer's disease pathology is common in older adults. To date, no symptomatic or disease-modifying pharmacological treatment has demonstrated efficacy in LATE. However, its clinical course appears to differ from that of typical Alzheimer's disease, with potentially slower progression and longer preservation of functional independence. LATE therefore represents a common and likely underrecognized cause of memory impairment in older adults, and its identification has important implications for diagnosis, prognosis, and therapeutic decision-making.},
}

@article {pmid42479744,
year = {2026},
author = {Bonarota, S and Caruso, G and Di Domenico, C and Di Lorenzo, F and Koch, G and Caltagirone, C and Bozzali, M and Serra, L},
title = {Are MMSE and ACE-R useful for detecting the earliest stages of Alzheimer's disease? A comparative study.},
journal = {Journal of neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jnp.70064},
pmid = {42479744},
issn = {1748-6653},
support = {//Ricerca Corrente 2026/ ; //Ministero della Salute-Ministry of Health/ ; },
abstract = {Subjective cognitive decline (SCD) is an at-risk condition for future cognitive decline, making its early identification crucial. We examined whether two widely used screening tools, the Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Mini Mental State Examination (MMSE), can distinguish SCD individuals from healthy elderly (HS) and from individuals with objective cognitive impairment. 110 participants were recruited: 22 HS, 25 SCD, 31 amnestic mild cognitive impairment (aMCI), and 32 Alzheimer's disease (AD) patients. All participants underwent an extensive neuropsychological battery and the ACE-R, which incorporates the MMSE. Partial ACE-R (ACER_P) scores were derived. Between-group comparisons were performed and discriminant analyses were run to evaluate sensitivity, specificity, and accuracy of total ACE-R (ACER_TOT), ACER_P, and MMSE. Despite no screening test significantly distinguishing SCD from HS, a progressive downward trend emerged across groups, with AD performing worst, followed by aMCI, then SCD and HS. Discriminant analyses indicated ACER_TOT had the highest sensitivity for AD (84.4%), with overall accuracy of 59.1%. Sensitivity for HS (68.2%) and aMCI (51.6%) was good but weaker. ACER_P and MMSE yielded similar or lower accuracy. Importantly, all measures poorly detected SCD, with sensitivity below 30%, leading to frequent misclassification as HS or aMCI. Although ACE-R and MMSE are moderately effective for identifying AD, HS and aMCI, they fail to distinguish SCD from other groups. Given the higher risk of SCD of being in AD continuum, such misclassification may prevent appropriate clinical follow-up. More sensitive screening instruments are needed to capture subtle cognitive changes and support early intervention strategies.},
}

@article {pmid42479987,
year = {2026},
author = {Ghorbani, E and Hajihashemi, S and Fahanik-Babaei, J and Nazari, M},
title = {Chronic 40-Hz Light-Emitting Diode (LED) Therapy Attenuates Cognitive and Behavioral Deficits and Modulates BDNF and Caspase-3 Expression in a D-galactose/Aluminum Chloride-Induced Sporadic Alzheimer's-Like Rat Model.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/00207454.2026.2706611},
pmid = {42479987},
issn = {1563-5279},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by gradual deterioration of cognition, synaptic integrity, and neuronal viability. Experimental exposure to D-galactose (D-gal) combined with aluminum chloride (AlCl3) produces oxidative and inflammatory damage within the brain, closely resembling AD-related neuropathology. Photobiomodulation therapy (PBMT) has recently gained attention as a safe, non-pharmacological approach with neuroprotective potential; however, the impact of sustained 40-Hz light-emitting diode (LED) stimulation in this context remains insufficiently explored.

METHODS: In the present study, rats received D-gal (60 mg/kg, i.p.) and AlCl3 (200 mg/kg, oral) for six weeks to induce AD-like changes. The treatment group was exposed to 40-Hz pulsed LED light (425-550 nm, 15 min/session, three times weekly). Behavioral analyses were performed using the elevated plus maze (EPM), novel object recognition (NOR), and passive avoidance (PA) paradigms. Western blotting quantified brain-derived neurotrophic factor (BDNF) and cleaved-caspase-3 expression in whole brain tissue.

RESULTS: D-gal/AlCl3 administration produced anxiety-like behavior, recognition deficits, and impaired memory retention, accompanied by decreased BDNF and elevated caspase-3. Remarkably, 40-Hz LED exposure reversed these alterations, up-regulating BDNF and suppressing caspase-3, in parallel with improvements in cognitive and emotional outcomes.

CONCLUSION: These data suggest that 40-Hz LED stimulation confers neuroprotection in the D-gal/AlCl3-induced AD model, potentially through enhancement of neurotropic signaling and inhibition of apoptosis, supporting its promise as a non-invasive strategy against neurodegenerative decline.},
}

@article {pmid42479989,
year = {2026},
author = {Magee, RG and Xie, SX and Ohm, DT and Rhodes, E and Massimo, L and Van Deerlin, VM and Wolk, DA and Lee, EB and Mcmillan, CT and Irwin, DJ},
title = {Association Between Postmortem Pathologic Burden and the Rate of Clinical Progression in Patients With Frontotemporal Lobar Degeneration.},
journal = {Neurology},
volume = {107},
number = {3},
pages = {e218278},
doi = {10.1212/WNL.0000000000218278},
pmid = {42479989},
issn = {1526-632X},
mesh = {Humans ; Female ; *Frontotemporal Lobar Degeneration/pathology ; *Disease Progression ; Male ; Middle Aged ; Retrospective Studies ; Aged ; tau Proteins/metabolism ; *Brain/pathology ; DNA-Binding Proteins/metabolism ; Longitudinal Studies ; Autopsy ; },
abstract = {BACKGROUND AND OBJECTIVES: Histopathologic staging of Alzheimer disease has led to validation of imaging techniques that guide diagnosis and treatment. We previously constructed preliminary phases of the sequential progression of TDP-43 and tau to guide similar efforts in behavioral-variant frontotemporal dementia (bvFTD). In this article, we expand this work using digital pathology and longitudinal clinical data to more comprehensively model the relationship between clinical progression and the distribution and severity of postmortem frontotemporal lobar degeneration (FTLD) pathology.

METHODS: In this retrospective cohort study, 101 patients (42% female, median age at symptom onset = 63 years) were selected from the Penn Integrated Neurodegenerative Disease Database and had both longitudinal assessments and primary neuropathologic diagnosis of FTLD-Tau or FTLD-TDP. We used validated methods to quantify the burden of primary pathology from up to 6 cortical regions across hemispheres. FTLD-TDP pathologic phase was constructed from diagnostic pathology data based on published criteria. We tested the association between pathologic metrics and (1) disease duration or (2) the rate of clinic progression measured by 2 independent global measures (Clinical Dementia Rating Scale-Sum of Boxes [CDR-SB] and Mini-Mental State Examination [MMSE]). Linear regression and linear mixed-effects models were adjusted for hemisphere sampled, sex, age at onset, pathogenic variant status, and pathologic subtype.

RESULTS: Disease duration did not associate with pathologic burden in multiple regression (FTLD-TDP β = 0.01 [-0.06, 0.09]; p = 0.7; FTLD-Tau β = 0.1 [-0.4, 0.7]; p = 0.7). By contrast, mean TDP-43 burden, but not FTLD-Tau burden, was associated with both worse relative CDR-SB (β = 0.1 [0.06, 0.2]; p = 0.0001) and MMSE (β = -0.1 [-0.2, -0.03]; p = 0.009) among all FTLD-TDP patients. TDP-43 phase also associated with worse CDR-SB (β = 0.07 [0.02, 0.1]; p = 0.005) and MMSE (β = -0.2 [-0.3, -0.1]; p = 0.000005). TDP-43 burden (CDR-SB (β = 0.1 [0.03, 0.2]; p = 0.005 and MMSE (β = -0.2 [-0.4, -0.05]; p = 0.009)), but not phase (CDR-SB (β = 0.02 [-0.03, 0.08]; p = 0.4 and MMSE (β = -0.04 [-1, 0.07]; p = 0.5)), associated with relative decline in sensitivity analyses limited to bvFTD.

DISCUSSION: Greater TDP-43 burden was most closely associated with antemortem clinical decline rather than cumulative aggregation through the disease course. These human data suggest that the temporal dynamics of protein aggregation may differ among FTLD proteinopathies, with implications for the interpretation of FTLD-Tau and FTLD-TDP‑specific biomarkers as these are developed.},
}

Humans
Female
*Frontotemporal Lobar Degeneration/pathology
*Disease Progression
Male
Middle Aged
Retrospective Studies
Aged
tau Proteins/metabolism
*Brain/pathology
DNA-Binding Proteins/metabolism
Longitudinal Studies
Autopsy