@article {pmid41533329,
year = {2026},
author = {Kim, AL and Lee, WK and Kwon, S and Han, I and Choi, BH},
title = {Therapeutic Efficacy of Mesenchymal Stem Cells (MSCs) on Alzheimer's Disease: Review of Clinical Results.},
journal = {Tissue engineering and regenerative medicine},
volume = {},
number = {},
pages = {},
pmid = {41533329},
issn = {2212-5469},
abstract = {BACKGROUND: Alzheimer's disease (AD) presents significant unmet medical needs with no effective therapeutic options. Current pharmacological treatments provide only symptomatic relief and do not prevent the ongoing neurodegeneration. Cell therapies using mesenchymal stem cells (MSCs) are being widely investigated for its potential in treating AD but remain unverified. This review aimed to evaluate therapeutic effects of MSCs on AD patients through a review of clinical trial literatures.

METHODS: Publications and registered clinical trials from January 2011 to June 2025 were collected from the international databases (ClinicalTrials.gov, PubMed, Web of Science, SCOPUS) using the keywords of "Alzheimer's disease", "mesenchymal stem cells", and "clinical trials". After initial screening and sorting, 17 clinical trials and 4 related papers were finally selected for in-depth analysis.

RESULTS: The 17 clinical trials were mostly early stages with 4 phase 1 (23.5%), 9 phases 1/2 (52.9%), 3 phase 2 (17.7%), and 1 pilot phase (5.9%). The source of MSCs included allogeneic umbilical cord blood (UCB) in 5 trials (29.4%), autologous adipose tissue in 4 (23.5%), allogeneic umbilical cord (UC) in 3 (17.6%), allogeneic bone marrow (BM) in 3 (17.6%), allogeneic placenta in 1 (5.9%) and 1 unknown (5.9%). Administration routes were primarily intravenous (IV) infusion in 12 trials (70.6%), intracerebroventricular (ICV) infusion via Ommaya reservoir in 3 (17.6%), and stereotactic brain injection (SBI) in 2 (11.8%). Among the 17 clinical trials, outcome data of 7 trials have been reported in 4 clinical papers and 1 clinical results posted in ClincalTrials.gov: 4 trials using UCB MSCs (NEUROSTEM-AD) in 2 papers, 2 trials using BM MSCs (Lomecel-B) in 2 papers and 1 trial using adipose MSCs (AstroStem) in ClinicalTrials.gov. All 5 reports using different cell types, administration routes or dosages claimed the safety of MSCs administration. As for the therapeutic efficacy, 2 reports using Lomecel-B reported meaningful improvement in AD pathophysiology or cognitive functions, while the other 3 reports using NEUROSTEM-AD or AstroStem failed to show statistically significant efficacy.

CONCLUSION: The analysis of 17 clinical trials and 5 relevant clinical outcomes showed that MSCs therapy if feasible and generally safe in AD patients. There are indications of potential therapeutic benefits such as improved cognitive function or quality of life measures in some AD patients. However, its therapeutic efficacy has not been proven definitely due to small size of subjects, variations in dosage, MSCs source, and administration scheme (route, timing, and frequency). Larger subject sizes and well-controlled trials are needed to provide more conclusive evidence.},
}

@article {pmid41533061,
year = {2026},
author = {Nakajima, K and Komatsu, J and Matsumura, T and Orimo, S and Yoshita, M and Frantellizzi, V and De Feo, MS and Greenfinch, G and Thomas, A and Assante, R and Acampa, W and Shirasaki, N and Yokoyama, K and Wakabayashi, H and Noguchi-Shinohara, M and Ono, K and Kinuya, S},
title = {Multicenter development and validation of a probability-based model to diagnose Lewy body disease using [123]I-meta-iodobenzylguanidine.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41533061},
issn = {1619-7089},
abstract = {PURPOSE: We previously proposed that a probability-based sympathetic [123]I-meta-iodobenzylguanidine (mIBG) index (SMILe) could distinguish the presence or absence of Lewy body disease (LBD) based on findings at a single center. However, whether the model would be useful in the real world remained uncertain. Therefore, we updated and evaluated its performance at five Japanese and three European institutions.

METHODS: We compared data from 967 patients with suspected LBD with 62 controls from a normal database (NDB). Of 815 patients with guideline-based diagnoses, 483 had LBD (Parkinson disease [PD] or dementia with Lewy bodies [DLB]) and 332 did not have LBD. Heart-to-mediastinum (H/M) ratios were standardized using a phantom-based method. Logistic regression models included early and late H/M ratios, age, sex, and comorbidities. We assessed diagnostic performance using ROC analysis and cross-validation.

RESULTS: The updated model discriminated LBD from other diseases (AUC for early and late H/M, 0.880 0.899, respectively). Age correction of H/M ratios based on the NDB did not improve accuracy. Median early H/M ratios [SMILe probability] were 3.09 [12.8%] for NDB, 2.57 [37.5%] for Alzheimer disease, 1.76 [84.7%] for PD, and 1.62 [89.0%] for DLB, with significantly lower H/M ratios and higher probabilities in PD and DLB compared with controls (p < 0.0001). Late-phase imaging added value mainly in intermediate borderline (30%-70%) situations. Coronary artery disease attenuated the diagnostic performance of SMILe.

CONCLUSION: The probability-based [123]I-mIBG model reliably differentiated LBD from other diseases. Standardization among sites supports global applicability and reflects real-world clinical practice.},
}

@article {pmid41533031,
year = {2026},
author = {Tan, FHP and Najimudin, N and Azzam, G and Zainuddin, A and Shamsuddin, S and Mohd Kasihmuddin, MS},
title = {Geroprotective effects of Salvianolic acid A through redox and detoxification pathway activation in an aging Drosophila Alzheimer's model.},
journal = {Biogerontology},
volume = {27},
number = {1},
pages = {39},
pmid = {41533031},
issn = {1573-6768},
mesh = {Animals ; *Alzheimer Disease/metabolism/drug therapy/genetics ; Drosophila melanogaster ; Disease Models, Animal ; *Aging/drug effects/metabolism ; Oxidation-Reduction ; Animals, Genetically Modified ; Oxidative Stress/drug effects ; Amyloid beta-Peptides/metabolism/genetics ; *Caffeic Acids/pharmacology ; *Lactates/pharmacology ; Humans ; *Neuroprotective Agents/pharmacology ; Longevity/drug effects ; Peptide Fragments ; },
abstract = {Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 (Aβ42) neurotoxic peptides that cause oxidative stress and neurodegeneration. The current study examined the neuroprotective properties of salvianolic acid A (SalA), an antioxidant polyphenol, in a Drosophila melanogaster model of AD. Transgenic flies expressing human Aβ42 were assayed for eye morphology, life span, and locomotor function after SalA diet supplementation. RNA-seq and RT-qPCR were used to quantify transcriptional regulation with SalA treatment. Aβ42 expression resulted in classic AD phenotypes, including retinal degeneration, shortened lifespan, and compromised climbing ability. Partial rescue of the rough-eye phenotype, significant prolongation of lifespan, and improved locomotor function in aging flies were induced by SalA treatment. Transcriptome profiling showed the upregulation of glutathione metabolism-associated, cytochrome P450 activity-associated, and antioxidant defence-associated genes, while muscle development-associated, cell adhesion-associated, and apoptosis-associated genes were downregulated. Network analysis identified a SalA-responsive gene module enriched in detoxification and immune pathways that was conducive to enhanced cellular resistance to Aβ42 toxicity. These findings identify a redox-regulated aging mechanism whereby SalA maintains neuronal and systemic homeostasis during aging. SalA inhibits Aβ42-induced neurotoxicity in Drosophila via promoting redox equilibrium and detoxification. These findings present SalA as a potential multi-target lead drug for AD and other age-related neurodegenerative diseases.},
}

Animals
*Alzheimer Disease/metabolism/drug therapy/genetics
Drosophila melanogaster
Disease Models, Animal
*Aging/drug effects/metabolism
Oxidation-Reduction
Animals, Genetically Modified
Oxidative Stress/drug effects
Amyloid beta-Peptides/metabolism/genetics
*Caffeic Acids/pharmacology
*Lactates/pharmacology
Humans
*Neuroprotective Agents/pharmacology
Longevity/drug effects
Peptide Fragments

@article {pmid41533007,
year = {2026},
author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Vining, KH and Thussananutiyakul, J and Spence, A and Nair, RM and Dunaief, JL and Mitchell, CH},
title = {PLGA Nanoparticles Restore Acidic pH and Degradative Function to Compromised Lysosomes with Cy3-Labeling Providing Enhanced Tracking to Lysosomes.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00494.2025},
pmid = {41533007},
issn = {1522-1563},
support = {EY013434//HHS | NIH | National Eye Institute (NEI)/ ; EY015537//HHS | NIH | National Eye Institute (NEI)/ ; EY001538//HHS | NIH | National Eye Institute (NEI)/ ; //Illinois Society for the Prevention of Blindness (ISPB)/ ; //Research to Protect Blindness/ ; //Penn Undergraduate Research Mentoring Program (PURM)/ ; //Eversight/ ; //Richard A Perritt MD Charitable Foundation/ ; //Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology/ ; //This work was partially supported by the Collaborative Research Grant (KV) from the Institute of Regenerative Medicine at the University of Pennsylvania& and the REgeneration and ReSToration of Function/ ; },
abstract = {Lysosomal dysfunction and elevated lysosomal pH are hallmark features of age-related neurodegenerative diseases including Age-related Macular Degeneration (AMD), Alzheimer's Disease (AD), and Parkinson's Disease (PD). Restoring lysosomal acidity is important for maintaining enzymatic degradation, preventing protein aggregation, and reducing cellular waste accumulation in degenerating tissues. Acidic nanoparticles represent a promising therapeutic strategy to normalize lysosomal pH; however, accurate monitoring of their delivery, retention, and dosage is critical for rigorous evaluation. To address this, we developed fluorescently labeled poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles conjugated with Cyanine3 amine (Cy3). Nanoparticle uptake was systematically optimized, achieving over 90% delivery to lysosomes of induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells. Uptake rates varied among adjacent cells. Once internalized, nanoparticles demonstrated remarkable stability, with no detectable change in concentration, distribution, or size for at least 28 days. iPS-RPE cells exhibited higher nanoparticle internalization compared to the ARPE-19 cell line and optic nerve head astrocytes. The capacity of the nanoparticles to restore function to stressed lysosomes was confirmed by their ability to reacidify lysosomes, restore cathepsin B activity and increase levels of active cathepsin D. The nanoparticles also reduced levels of LC3II in astrocytes treated with chloroquine, indicating they can also restore autophagy rates. In summary, this study demonstrates the value of Cy3 labeling for enhanced nanoparticle tracking to lysosomes. The findings also identify PLGA nanoparticles as powerful tools for restoring degradative lysosomal function and autophagy in cells undergoing lysosomal stress.},
}

@article {pmid41532955,
year = {2026},
author = {Bernal-Vicente, BN and Ponce, I and Ríos-Castro, E and Moreno-Castilla, P and Tovar-Y-Romo, LB},
title = {Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection.},
journal = {Journal of neurochemistry},
volume = {170},
number = {1},
pages = {e70350},
doi = {10.1111/jnc.70350},
pmid = {41532955},
issn = {1471-4159},
support = {IN214723//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Proteomics/methods ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Neuroprotection/physiology ; Biomarkers/metabolism ; },
abstract = {Extracellular vesicles (EVs) are instrumental mediators of intercellular communication and molecular exchange in neurodegenerative and neurovascular diseases. This review integrates recent advances in EV proteomics to elucidate their roles in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and ischemic stroke. Across these conditions, EVs carry disease-relevant proteins that reflect and influence key pathological processes such as synaptic dysfunction, neuroinflammation, blood-brain barrier (BBB) disruption, and cell death. Proteomic profiling of brain- and biofluid-derived EVs has uncovered specific biomarkers and signaling pathways, ranging from tau and α-synuclein in AD and PD to mutant SOD1 in ALS and complement activation in stroke and TBI. Moreover, cell-type-specific EVs (e.g., from neurons, astrocytes, microglia, and stem cells) have been shown to exert either protective or deleterious effects, modulating apoptosis, axonal regeneration, and immune responses. Recent evidence highlights the translational potential of EVs as non-invasive biomarkers and therapeutic vectors across multiple disorders. By mapping shared and divergent proteomic signatures in EVs, we review the mechanistic relevance and clinical utility of EVs in neurodegeneration and CNS injury.},
}

Humans
*Extracellular Vesicles/metabolism
*Proteomics/methods
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Neuroprotection/physiology
Biomarkers/metabolism

@article {pmid41532810,
year = {2026},
author = {Pentchev, JV and Jackson, T and Khan, N and Rosewood, TJ and Huang, YN and Nho, K and Saykin, AJ and Eloyan, A and Taurone, A and Thangarajah, M and Riddle, M and Salloway, S and Atri, A and Honig, LS and Johnson, ECB and Turner, RS and Masdeu, JC and Foroud, TM and Clark, D and Hammers, DB and Dage, JL and Kirby, K and Ghetti, B and Newell, K and Onyike, CU and Day, GS and Graff-Radford, NR and Murray, ME and Jones, DT and Jack, CR and Vemuri, P and Touroutoglou, A and Duara, R and Grant, I and Sha, S and Wingo, TS and Beckett, LA and Rogalski, E and Mendez, MF and Kramer, J and La Joie, R and Blazhenets, G and Grinberg, LT and Koeppe, R and Wolk, DA and Aisen, P and Raman, R and Toga, A and Kukull, WA and Musiek, E and Womack, KB and Carrillo, MC and Rabinovici, GD and Dickerson, BC and Apostolova, LG and Nudelman, KNH and , },
title = {Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71066},
doi = {10.1002/alz.71066},
pmid = {41532810},
issn = {1552-5279},
support = {(AARG)-22-926940//Alzheimer's Association research/ ; LDRFP-21-818464//Alzheimer's Association research/ ; GENETICS-19-639372//Alzheimer's Association research/ ; R56AG057195/NH/NIH HHS/United States ; U01AG6057195/NH/NIH HHS/United States ; U24AG021886/NH/NIH HHS/United States ; U01AG016976/NH/NIH HHS/United States ; P30AG010133/NH/NIH HHS/United States ; P30AG072976/NH/NIH HHS/United States ; P50AG008702/NH/NIH HHS/United States ; P50AG025688/NH/NIH HHS/United States ; P50AG005146/NH/NIH HHS/United States ; P30AG062421/NH/NIH HHS/United States ; P30AG062422/NH/NIH HHS/United States ; P50AG023501/NH/NIH HHS/United States ; P30AG010124/NH/NIH HHS/United States ; P30AG066506/NH/NIH HHS/United States ; P30AG013854/NH/NIH HHS/United States ; P50AG005681/NH/NIH HHS/United States ; P50AG047366/NH/NIH HHS/United States ; U24AG021886/NH/NIH HHS/United States ; U19AG024904/NH/NIH HHS/United States ; W81XWH-12-2-0012//U.S. Department of Defense/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/cerebrospinal fluid/diagnostic imaging ; Male ; Female ; *Multifactorial Inheritance/genetics ; Aged ; Biomarkers/cerebrospinal fluid ; Age of Onset ; Longitudinal Studies ; Amyloid beta-Peptides/cerebrospinal fluid ; Apolipoprotein E4/genetics ; Neuroimaging ; Cognitive Dysfunction/genetics ; Synaptosomal-Associated Protein 25/cerebrospinal fluid ; Brain/diagnostic imaging ; Genetic Predisposition to Disease ; Risk Factors ; Aged, 80 and over ; Middle Aged ; },
abstract = {INTRODUCTION: The genetic basis of sporadic early-onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late-onset Alzheimer's disease (LOAD) polygenic risk in EOAD.

METHODS: A LOAD polygenic score (PGS) was calculated in the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers.

RESULTS: Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset (p = 0.106) or with cognitive performance (p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal-associated protein 25 (SNAP-25) (p = 2.3 × 10[-5]).

DISCUSSION: While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology.

HIGHLIGHTS: LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal-associated protein 25 (SNAP-25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.},
}

Humans
*Alzheimer Disease/genetics/cerebrospinal fluid/diagnostic imaging
Male
Female
*Multifactorial Inheritance/genetics
Aged
Biomarkers/cerebrospinal fluid
Age of Onset
Longitudinal Studies
Amyloid beta-Peptides/cerebrospinal fluid
Apolipoprotein E4/genetics
Neuroimaging
Cognitive Dysfunction/genetics
Synaptosomal-Associated Protein 25/cerebrospinal fluid
Brain/diagnostic imaging
Genetic Predisposition to Disease
Risk Factors
Aged, 80 and over
Middle Aged

@article {pmid41532803,
year = {2026},
author = {Rudroff, T},
title = {Population diversity validation for Alzheimer's disease "unifying" models.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71070},
doi = {10.1002/alz.71070},
pmid = {41532803},
issn = {1552-5279},
}

@article {pmid41532798,
year = {2026},
author = {Kass, B and Poschmann, G and Demir, F and Huesgen, P and Stühler, K and Kutzsche, J and Willbold, D},
title = {The Proteome of Human Amyloid Beta Oligomers.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00597},
pmid = {41532798},
issn = {1520-4995},
abstract = {Amyloid beta (Aβ) oligomers are thought to play an important role during development and progression of Alzheimer's disease (AD). Previously, we determined the Aβ oligomer concentrations in various AD mouse models and in human brain tissues of former AD patients. Here, we investigate which proteins are part of these Aβ oligomers, apart from Aβ itself. Because several oligomer-associated proteins have been implicated in mechanisms leading to AD pathology, identification of the Aβ oligomer proteome may provide insights into the formation of Aβ oligomers in vivo and may reveal novel targets for disease-modifying therapeutic approaches. Here, we separated different native Aβ assemblies in brain homogenates of transgenic (tg) AD mice and human AD post mortem samples by density gradient centrifugation, then isolated Aβ-containing assemblies by co-immunoprecipitation. Mass spectrometry of immunoprecipitated proteins with label-free quantification (LFQ) showed significant changes between the proteomes of Aβ oligomers from tg AD mice and wildtype (wt) mice, confirming some proteins that have been expected to bind Aβ species, like ApoE and Clusterin, but also indicating novel, so far unknown, protein content of Aβ oligomers, such as the RabGAP Tbc1d10b. Some of the hereby identified proteins, like, for example, Clusterin, were also found to be enriched in Aβ oligomers from human AD brain tissue derived homogenates as compared to brain tissue from non-demented controls (NC). Others, such as Netrin-1, were specifically enriched in Aβ oligomers in AD compared to NC samples, but not in mouse samples.},
}

@article {pmid41532783,
year = {2026},
author = {Coleman, PD and Delvaux, E and Boehringer, A and Huseby, CJ},
title = {Regarding the importance of population diversity validation in Alzheimer's disease models.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71071},
doi = {10.1002/alz.71071},
pmid = {41532783},
issn = {1552-5279},
}

@article {pmid41532780,
year = {2026},
author = {Alasmar, Z and Tremblay, C and Moqadam, R and Serrano, GE and Beach, TG and Atri, A and Su, Y and , and Zeighami, Y and Dadar, M},
title = {Gray matter microstructure from in vivo diffusion magnetic resonance imaging reflects post mortem neuropathology severity and clinical progression of Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71037},
doi = {10.1002/alz.71037},
pmid = {41532780},
issn = {1552-5279},
support = {//Natural Sciences and Engineering Research Council of Canada (NSERC) Vanier Scholars program/ ; //Canadian Institutes of Health Research (CIHR)/ ; //FRQS, NSERC, CIHR, and Brain Canada/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/diagnostic imaging/genetics ; Female ; Male ; Disease Progression ; *Diffusion Magnetic Resonance Imaging ; Aged ; *Gray Matter/pathology/diagnostic imaging ; Aged, 80 and over ; Autopsy ; *Brain/pathology/diagnostic imaging ; Cognitive Dysfunction/pathology ; Cross-Sectional Studies ; },
abstract = {INTRODUCTION: Diffusion-weighted imaging derived mean diffusivity (MD) correlates with Alzheimer's disease (AD) biomarkers, yet its neuropathological correlates remain unclear.

METHODS: Diffusion-weighted imaging, post mortem neuropathology, and cognitive performance data were obtained from the National Alzheimer's Coordinating Center (N = 97), Alzheimer's Disease Neuroimaging Initiative (N = 21), and Arizona Study of Aging and Neurodegenerative Disorders (N = 15). We examined MD associations with neuropathology, cognitive decline, and expression profiles of AD-implicated genes.

RESULTS: Results revealed two latent variables-one linked to amyloid/tau, the other to vascular pathology-explaining between 70% and 16% of MD-pathology covariance, respectively. Higher MD correlated with worse cognitive performance, both cross-sectionally and up to 16 years prior to death. MD was regionally associated with Thal phase, neuritic plaque density, Braak stage (temporal/limbic), and infarcts (thalamus), and reflected gene expression patterns related to AD.

DISCUSSION: In vivo MD captures distinct AD-related pathologies across brain regions and relates to cognitive trajectories and gene expression.

HIGHLIGHTS: Diffusion-weighted imaging (DWI) can detect early gray matter microstructural differences in the Alzheimer's disease (AD) continuum. Mean diffusivity (MD) is associated with tau, amyloid and vascular neuropathologies. Thal amyloid phase and Braak tau score correlate with MD in temporal and limbic regions. Multivariate MD scores differentially relate to proteinopathies vs. vascular damage. MD can serve as a non-invasive biomarker to predict post mortem AD neuropathology.},
}

Humans
*Alzheimer Disease/pathology/diagnostic imaging/genetics
Female
Male
Disease Progression
*Diffusion Magnetic Resonance Imaging
Aged
*Gray Matter/pathology/diagnostic imaging
Aged, 80 and over
Autopsy
*Brain/pathology/diagnostic imaging
Cognitive Dysfunction/pathology
Cross-Sectional Studies

@article {pmid41532696,
year = {2026},
author = {Han, J and Jeong, JH and Lee, D and Jung, Y and Jin, Y and Jung, ES and Kim, HJ and Kim, WY and Lee, CH and Mook-Jung, I},
title = {Dual Targeting of Tau Kinases and Autophagy by Abemaciclib Independent of CDK4/6 Inhibition.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e13135},
doi = {10.1002/advs.202513135},
pmid = {41532696},
issn = {2198-3844},
support = {2025-RISE-01-016-01//Ministry of Education/ ; RS-2020-KH106773//Korea Dementia Research Center/ ; RS-2020-KH106747//Korea Dementia Research Center/ ; },
abstract = {Alzheimer's disease (AD) is marked by progressive cognitive decline driven largely by tau pathology, yet disease-modifying therapies targeting tau remain limited. In this study, we re-evaluated abemaciclib, a clinically approved CDK4/6 inhibitor for breast cancer and uncovered its previously unrecognized therapeutic potential in AD via CDK4/6-independent mechanisms. Using the APP[NL-F]/MAPT double knock-in mouse model (dKI) and AD patient-derived brain organoids, we found that abemaciclib robustly ameliorates cognitive deficits and reduces neurodegeneration without altering amyloid burden or glial activation. Mechanistically, abemaciclib selectively inhibited key tau kinases, particularly Ca[2][+]/calmodulin-dependent protein kinase II (CaMKII) and glycogen synthase kinase 3β (GSK3β), independent of CDK4/6 inhibition, as confirmed by lentiviral knockdown experiments. Furthermore, abemaciclib enhanced autophagic flux and lysosomal activity, promoting clearance of pathological tau proteins. This dual modulation-suppression of tau phosphorylation and facilitation of degradation-highlights abemaciclib as a promising repurposed therapeutic for AD. Our findings establish a novel pharmacological profile for abemaciclib beyond its canonical role in cell cycle control, offering immediate translational potential for tau-targeted AD therapy.},
}

@article {pmid41532588,
year = {2026},
author = {Trammell, AR and Dorbin, CD and Davis, CP and Manzanares, CM and Xu, H and Zhao, L and Hanfelt, JJ and Alonso, A and Goldstein, FC and Hales, CM and Golde, TE and Levey, AI and Parker, MW and Lah, JJ},
title = {Successful strategies for supporting diverse representation in Alzheimer's disease research.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70941},
doi = {10.1002/alz.70941},
pmid = {41532588},
issn = {1552-5279},
support = {R01AG070937//National Institute on Aging/ ; P30AG066511//National Institute on Aging/ ; },
mesh = {Humans ; *Alzheimer Disease ; Female ; Male ; Aged ; Black or African American/statistics & numerical data ; *Biomedical Research ; White People/statistics & numerical data ; Cohort Studies ; *Patient Selection ; Aged, 80 and over ; Middle Aged ; Health Education ; White ; },
abstract = {INTRODUCTION: The Emory Goizueta Alzheimer's Disease Research Center implemented targeted, community-based programs emphasizing health education and collaboration with community partners. This paper reports on their impact on research enrollment and the lessons learned.

METHODS: We analyzed attendance data from in-person events for new participants in the Uniform Data Set (UDS) cohort. Using regression modeling, we examined relationships among demographics and time to UDS enrollment.

RESULTS: From 2016 to 2024, 194 adults enrolled in the UDS. They were mostly women (59%), evenly divided between African American (AA; 54%) and non-Hispanic White (NHW; 46%) individuals, and well-educated (median 16 years). Before consent, more AA participants attended events (82.7% vs. 42.0%; p < 0.0001) and a greater number of events (median 2, interquartile range [IQR]: 1-4 vs. 0, IQR: 0-2; p < 0.0001) than their NHW peers. Among all race-gender groups, the time to enrollment was shortest for AA men.

DISCUSSION: Collaborative, community-based, structured outreach initiatives with focused content can influence research engagement.

HIGHLIGHTS: Despite higher dementia risk, older adults from understudied populations have low enrollment in aging and cognition studies, limiting the generalizability of knowledge about biomarkers and related mechanisms. Besides socioeconomic factors, disproportionate exclusion from screening criteria, less access to expert care, and fewer professional referrals are linked to lower research participation rates. Intentional recruitment activities that incorporate educational content and target community input about health challenges can enhance engagement and promote more representative cohorts, including understudied populations.},
}

Humans
*Alzheimer Disease
Female
Male
Aged
Black or African American/statistics & numerical data
*Biomedical Research
White People/statistics & numerical data
Cohort Studies
*Patient Selection
Aged, 80 and over
Middle Aged
Health Education
White

@article {pmid41532473,
year = {2026},
author = {Li, HL and Ohmiya, H and Sakamoto, S and Yugami, M and Oki, A and Furusawa, M and Ling, Y},
title = {Microglial dynamics and ferroptosis induction in human iPSC-derived neuron-astrocyte-microglia tri-cultures.},
journal = {FEBS open bio},
volume = {},
number = {},
pages = {},
doi = {10.1002/2211-5463.70182},
pmid = {41532473},
issn = {2211-5463},
support = {//Takeda Pharmaceutical Company/ ; },
abstract = {The dynamics of microglial activity within neuron-astrocyte-microglia tri-cultures derived from human induced pluripotent stem cells (iPSCs) present a complex interplay and offer an opportunity to obtain new insights into neuron-glia interactions. Iron-laden microglia, correlating with functional changes, represent a key pathological feature of Alzheimer's disease (AD). This study characterized the cellular crosstalk and transcriptional states of microglia in tri-cultures. Complement C3 can be detected in culture media when microglia are cocultured with neurons, and the addition of astrocytes in the coculture led to an increased amount of C3, indicating that the impact of glial interactions can be evaluated in this model system. We compared microglial gene expression profiles comprehensively in monoculture, coculture, and tri-culture settings. Single-cell RNA sequencing (scRNA-seq) revealed various microglial states with gene expression changes associated with endocytosis and neuron-related functions in tri-culture settings, suggesting that microglial behavior is profoundly impacted by the presence of neurons and astrocytes. We assessed microglial responses to iron overload combined with the ferroptosis inducer RSL3 (a GPX4 inhibitor) in tri-cultures. Microglial cell death was accompanied by ferritin heavy-chain expression, indicating microglia ferroptosis. scRNA-seq analyses highlighted alterations in pathways related to ferroptosis, stress response, and autophagy, indicating substantial shifts in microglial profiles upon iron perturbation. These findings underscore the necessity of using tri-cultures as a model to capture certain degrees of complex cellular interactions occurring in vivo. These results offer critical insights for establishing in vitro models for therapeutic development of neurodegenerative diseases, including AD.},
}

@article {pmid41532468,
year = {2026},
author = {Lu, H and Yang, D and Shi, Y and Wang, J},
title = {Letter to the Editor about mortality from Alzheimer's disease and other dementias and its heterogeneity across states in India: findings from GBD 2021 study.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000004722},
pmid = {41532468},
issn = {1743-9159},
}

@article {pmid41532445,
year = {2026},
author = {Henry, L and Bhattacharya, S and Bergaglio, T and Pinotsi, D and Nirmalraj, PN},
title = {Differentiating Alzheimer's Aβ Isoforms Coaggregated in Cerebrospinal Fluid via Single-Particle Imaging.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00692},
pmid = {41532445},
issn = {1948-7193},
abstract = {Amyloid polymorphism can reflect Alzheimer's disease (AD) stages. This paper demonstrates that amyloid β (Aβ) peptides, primarily Aβ-40 and Aβ-42 (implicated in AD pathology), present in cerebrospinal fluid (CSF), can be differentiated, and their morphology studied in detail using fluorescence-based super-resolution and atomic force microscopy (AFM). An inhibitory effect of Aβ-40 on Aβ-42 protein aggregation, marked by Aβ-40 oligomers colocalizing along the Aβ-42 fibril backbone, was resolved at the single-particle level. Molecular dynamics simulations revealed that coaggregation is modulated by the ionic environment in CSF, where calcium ions form bridges between Glu residues of Aβ-40 and Aβ-42, known to stabilize the fibril structure. This ion-mediated tethering compacts Aβ-40 and kinetically traps the fibril-oligomer interface, thus reducing fibril elongation. The isoform-specific imaging method further allowed us to distinguish Aβ-40 and Aβ-42 aggregates from oligomers to mature fibrils in the CSF of AD patients, and the nanoscopic differences in aggregate sizes were quantified from the AFM topographs. Such a protein characterization approach, which is not limited by analyte size or shape and is capable of fingerprinting Aβ aggregates in CSF, could be used in clinical settings to monitor the progression of Alzheimer's disease and related pathologies.},
}

@article {pmid41532391,
year = {2026},
author = {Sanchez-Todo, R and Mercadal, B and Lopez-Sola, E and Guasch-Morgades, M and Deco, G and Ruffini, G},
title = {Fast Interneuron Dysfunction in Laminar Neural Mass Model Reproduces Alzheimer's Oscillatory Biomarkers.},
journal = {Human brain mapping},
volume = {47},
number = {1},
pages = {e70428},
doi = {10.1002/hbm.70428},
pmid = {41532391},
issn = {1097-0193},
support = {855109//H2020 European Research Council/ ; 101017716//H2020 Future and Emerging Technologies/ ; },
mesh = {*Interneurons/physiology/metabolism ; *Alzheimer Disease/physiopathology/metabolism ; Humans ; *Models, Neurological ; *Pyramidal Cells/physiology ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; Parvalbumins/metabolism ; *Brain Waves/physiology ; *Cerebral Cortex/physiopathology ; },
abstract = {Early-stage AD involves cortical hyperexcitability, progressing to oscillatory slowing and hypoactivity. These changes are linked to parvalbumin-positive (PV $$ PV $$) interneuron dysfunction and neuronal loss driven by amyloid-beta (Aβ $$ \mathrm{A}\
upbeta $$) and hyperphosphorylated tau (hp- τ $$ \tau $$), though underlying mechanisms remain unclear. To investigate this relationship, we employed a Laminar Neural Mass Model integrating excitatory and inhibitory populations. Synaptic coupling from PV $$ PV $$ interneurons to pyramidal cells was progressively reduced to mimic Aβ $$ \mathrm{A}\
upbeta $$ -induced neurotoxicity. Additional parameter variations simulated alternate mechanisms, including hp-tau pathology. Simulated dipole activity was analyzed in the time-frequency domain and compared to the literature. Simulating PV $$ PV $$ interneuron dysfunction reproduced AD's biphasic progression: early hyperexcitability with elevated gamma and alpha power, followed by oscillatory slowing and reduced spectral power. Alternative mechanisms, such as increased excitatory drive, did not replicate this trajectory. To account for late-stage hypoactivity and reduced firing rates, we incorporated pyramidal cell disruption consistent with hp- τ $$ \tau $$ neurotoxicity. While not essential for local oscillatory changes, this addition aligns the model with empirical markers of advanced AD and supports whole-brain modeling. These findings highlight PV $$ PV $$ interneuron dysfunction as a primary mechanism of early electrophysiological disruption in AD, with pyramidal cell loss contributing to late-stage hypoactivity, offering a mechanistic model for excitation-inhibition imbalance across progression.},
}

*Interneurons/physiology/metabolism
*Alzheimer Disease/physiopathology/metabolism
Humans
*Models, Neurological
*Pyramidal Cells/physiology
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism
Parvalbumins/metabolism
*Brain Waves/physiology
*Cerebral Cortex/physiopathology

@article {pmid41532120,
year = {2026},
author = {Ladurner, G and Merkle, CW and May, L and Worm, S and Patel, Y and Varaka, M and Daurer, M and Jauk, L and Rabl, R and Königshofer, P and Garhöfer, G and Prokesch, M and Baumann, B},
title = {Longitudinal investigation of spatial memory and retinal parameters in a 5xFAD model of Alzheimer's disease reveals differences dependent on genotype and sex.},
journal = {Biomedical optics express},
volume = {17},
number = {1},
pages = {405-426},
doi = {10.1364/BOE.579020},
pmid = {41532120},
issn = {2156-7085},
abstract = {The retinal phenotype of Alzheimer's disease (AD), its connection to spatial memory, and the influence of sex on the phenotype are poorly understood. Here, we investigate the retina and spatial memory of 5xFAD mouse models of AD by measuring retinal and behavioral parameters. A custom-built optical coherence tomography (OCT) system is used to image the retina of 32 transgenic and 32 non-transgenic 5xFAD mice over the course of 6 months (3-9 months of age). The Morris water maze (MWM) test was performed to examine correlations between the retinal and spatial memory phenotype of the mouse model. Total retinal and inner retinal layer thickness increased slightly over the measurement period, while outer retinal layer and retinal nerve fiber layer thickness showed no significant change. The correlation analysis between MWM and layer thickness data revealed a positive correlation between inner nuclear layer thickness and spatial memory capabilities. OCT and MWM data revealed sex-based differences in the retinal phenotype of the 5xFAD mouse model, with changes in retinal thickness in different stages of the study and dissimilar correlations between retinal and spatial memory phenotype.},
}

@article {pmid41532087,
year = {2025},
author = {Goldman, AW and Finlay, J and Bea, MD},
title = {Associations between U.S. County-Level Social Infrastructure and Dementia among Medicare Beneficiaries, 2020.},
journal = {Alzheimer's & dementia. Behavior & socioeconomics of aging},
volume = {1},
number = {3},
pages = {},
doi = {10.1002/bsa3.70029},
pmid = {41532087},
issn = {2997-3805},
abstract = {INTRODUCTION: Spatial and social-environmental factors influence individual cognition and dementia risk, but the role of social infrastructure in geographic dementia disparities remains underexplored.

METHODS: We used 2020 Medicare claims data from the Dementia DataHub and 2003-2017 business and establishment data from the National Establishment Time Series Database in spatial autoregressive models to examine associations between county-level social infrastructure and county-level dementia rates.

RESULTS: Higher densities of civic organizations were associated with lower county dementia incidence, while museums and recreational facilities were associated with lower prevalence and incidence. Religious organizations were associated with significantly higher rates. County urbanicity moderated the effects of recreational facilities, senior centers, libraries, and coffee shops.

DISCUSSION: Types of social infrastructure may help address dementia and related needs by providing social, educational, and other cognitively-protective resources to county residents. Social infrastructure warrants further attention as an area for local investment to reduce geographic disparities in dementia.},
}

@article {pmid41532084,
year = {2026},
author = {Carvalho, PC and Voltolini, GB and Goedert, A and Chiaratti, VKC and Cantarelli, EH and Francisco, JC and Almeida, TB and Burigo, IP},
title = {Hospitalizations due to Alzheimer's disease in Brazil during the COVID-19 pandemic: an update on frequency, mortality, and costs.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250322},
doi = {10.1590/1980-5764-DN-2025-0322},
pmid = {41532084},
issn = {1980-5764},
abstract = {UNLABELLED: Hospitalizations related to Alzheimer's disease (AD) impose a growing burden on health systems, but recent, nationally representative estimates for Brazil are limited.

OBJECTIVE: To describe the epidemiological profile of hospital admissions due to AD in Brazil from 2018 to 2024.

METHODS: Ecological time-series study using the Hospital Information System of the Brazilian Unified Health System (SIH/SUS), accessed via the Department of Informatics of the SUS (DATASUS). We included all regions and states from January 2018 to December 2024. Admissions were identified by the International Classification of Diseases, 10[th] Revision (ICD-10) codes G30.0-G30.9 and F00.0-F00.9. Variables comprised sex, age group, race/color, admission type (urgent/elective), in-hospital mortality, length of stay, and hospital costs. Temporal trends were evaluated with linear regression.

RESULTS: From 2018 to 2024, 11,212 AD-related hospitalizations were recorded; 79.4% were urgent. The Southeast had the highest absolute number (47.8%), followed by the South (25.1%), Northeast (17.2%), Midwest (6.5%), and North (3.4%). Females accounted for 65% of admissions and 64.7% of in-hospital deaths. Older adults, especially those ≥80 years, represented most hospitalizations (59.3%) and deaths (69.7%). Total hospital expenditures exceeded R$ 14 million, with the Southeast concentrating >60% of national costs. No significant linear trend was detected in annual rates.

CONCLUSION: Urgent admissions comprised the majority of AD hospitalizations nationwide, with the Southeast presenting the highest numbers. The predominance of older female patients and high in-hospital mortality underscore the need for targeted clinical and public health strategies. Rising expenditures reinforce investment in health infrastructure and long-term dementia-care policies in Brazil.},
}

@article {pmid41532083,
year = {2026},
author = {de Sousa, ÍA and Costa, BHC and de Almeida, IJ and Carthery-Goulart, MT and de Brito, MH and de Holanda, MM and Perroco, TR and Magaldi, RM and Brucki, SMD},
title = {Logopenic variant of primary progressive aphasia in a bilingual non-Alzheimer's disease octogenarian.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250379},
doi = {10.1590/1980-5764-DN-2025-0379},
pmid = {41532083},
issn = {1980-5764},
abstract = {A highly educated and intellectually active 84-year-old male presented with word-finding pauses and impaired sentence repetition, with preserved single-word comprehension, reading, and writing, a clinical profile consistent with the logopenic variant of primary progressive aphasia (lvPPA). Interestingly, the initial symptom was difficulty with auditory verbal comprehension in Portuguese, his second language, while comprehension in English remained initially preserved. Structural and functional imaging revealed no atrophy in the temporoparietal region or cortical hypometabolism. Plasma biomarkers, including Aβ42/40 and plasma-measured tau phosphorylated at threonine 217 (p-tau217), were within normal limits, arguing against biological Alzheimer's disease (AD). This case illustrates a rare constellation of findings - bilingual asymmetry, negative AD biomarkers, and unremarkable neuroimaging - suggestive of a non-Alzheimer's pathology. Alternative etiologies such as primary age-related tauopathy (PART) and argyrophilic grain disease (AGD) are discussed, emphasizing the utility of fluid biomarkers in distinguishing phenocopies within the lvPPA spectrum.},
}

@article {pmid41531988,
year = {2025},
author = {Benin, BM and Hillyer, T and Csubak, BA and Aguirre, N and Dengler-Crish, CM and Kang, C and Shin, WS},
title = {Investigation of Three Flavonoids as Potent Tau Aggregation Inhibitors and In vivo Demonstration of Myricetin.},
journal = {Pharmacological research. Natural products},
volume = {9},
number = {},
pages = {},
doi = {10.1016/j.prenap.2025.100449},
pmid = {41531988},
issn = {2950-1997},
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), are characterized by the formation and propagation of neurotoxic tau aggregates, which arise from the misfolding and subsequent aggregation of tau proteins into fibrillary structures. While tau-targeting agents represent a promising therapeutic strategy for the prevention and treatment of various neurodegenerative diseases, they currently constitute a limited subset of the treatments undergoing clinical trials. In this study, we report the potent anti-aggregation and filament disassembly effects of three flavonols: myricetin, quercetagetin, gossypetin. We observed remarkable nanomolar-to-low-micromolar 50% inhibitory concentrations (0.57-1.21μM) and low 50% disassembly concentrations (7.5-14μM) using tau seeds derived from AD mouse model brains. Furthermore, we validated that myricetin treatment was associated with a reduction in overall phosphorylated tau (p-Tau) burden in vivo in the 3xTg AD mouse model. Notably, these reductions were associated with enhanced performance in Y-maze assessments of spatial learning and memory, supporting further preclinical evaluation, including direct brain pharmacokinetic studies and mechanism-driven investigations relevant to tauopathy therapy.},
}

@article {pmid41531973,
year = {2026},
author = {Sabnis, RW and Sabnis, AR},
title = {Novel Compounds as TREM2 Agonists for Treating Alzheimer's Disease.},
journal = {ACS medicinal chemistry letters},
volume = {17},
number = {1},
pages = {97-98},
doi = {10.1021/acsmedchemlett.5c00751},
pmid = {41531973},
issn = {1948-5875},
abstract = {Provided herein are novel compounds as TREM2 agonists, pharmaceutical compositions, use of such compounds in treating Alzheimer's disease, and processes for preparing such compounds.},
}

@article {pmid41531953,
year = {2026},
author = {Osama, A and Ji, M and Fang, J and Zhao, H and Zhang, B},
title = {Emergence of a Potent AChE Inhibitor with Antioxidant and Neuroprotection Abilities.},
journal = {ACS medicinal chemistry letters},
volume = {17},
number = {1},
pages = {137-143},
doi = {10.1021/acsmedchemlett.5c00524},
pmid = {41531953},
issn = {1948-5875},
abstract = {Oxidative damage and cholinergic dysfunction are common pathological features of Alzheimer's disease (AD). Maintaining the redox balance of neurons and cholinergic signaling through antioxidants and acetylcholinesterase (AChE) inhibition may provide therapeutic benefits for AD. In this regard, we discovered three AChE inhibitors with more potency than the positive control (rivastigmine; IC50 = 24.5 μM). Among these active compounds, C5 (a flavonoid derivative) was the most potent AChE inhibitor with an IC50 of 5.02 μM, followed by C1, C6, and C2 with IC50 values of 7.94 μM, 8.13 μM, and 27.52 μM, respectively. Compound C5 also demonstrated strong neuroprotective activity, rescuing PC12 cells from H2O2-induced damage and scavenging various ROS models. Interestingly, C5 also prevented memory impairments in the scopolamine-induced cognitive dysfunction zebrafish model. Our findings suggest that C5 is a potential drug lead for cholinergic dysfunction-related disorders such as AD.},
}

@article {pmid41531938,
year = {2026},
author = {Mandloi, U and Giri, N and Kumar, S and Modi, G},
title = {Theranostic advances in Alzheimer's disease: structure-guided design of near-infrared fluorescent probes targeting amyloid-β and cholinergic dysfunction.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5md00713e},
pmid = {41531938},
issn = {2632-8682},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder, with unmet clinical challenges due to the lack of early diagnosis and an efficient treatment. Theranostics, an integrated approach that combines diagnosis and therapy, has emerged as a viable option, particularly with the use of near-infrared fluorescence probes (NIRFPs), which allow real-time in vivo imaging and therapeutic monitoring. This review article discusses recent breakthroughs in the rational design of alkene-bridged donor-π-acceptor (D-π-A) NIRFPs that target AD hallmarks such as amyloid-β (Aβ) aggregation and cholinergic dysfunction. We specifically focused on multifunctional probes like THK-565 (fluorescent compound), and a dihydrotetramethyl-indocyanine theranostic near-infrared probe (DTNP), which exhibit high blood-brain barrier (BBB) permeability, target selectivity, and dual imaging/therapeutic capabilities. Furthermore, emerging probes can distinguish between Aβ and cholinesterase (ChEs) with high resolution and low toxicity. Together, these molecular imaging technologies provide a game-changing platform for detection of early-stage AD and multiple intervention approaches. We explore structure-activity connections, molecular processes, and future directions for the clinical translation of NIRFP-based theranostic agents in AD.},
}

@article {pmid41531926,
year = {2025},
author = {Jerath, R and Malani, V},
title = {The fading self in space-disruption of default spatial representation across neurological disorders.},
journal = {Frontiers in systems neuroscience},
volume = {19},
number = {},
pages = {1655500},
doi = {10.3389/fnsys.2025.1655500},
pmid = {41531926},
issn = {1662-5137},
abstract = {Neurological disorders stem from an intermingled change to self-in-space. While many of these disorders present as spatial deficits-contralateral neglect syndrome, for example-they manifest from the same etiology: disruption to the brain's "default spatial representation" (DSR). DSR is a basic internally generated representation of space that delineates where the self is located in space-without attentional focus from an external drive. We review how pathologic disintegration of DSR is associated with anomalous activation and connectivity within distinct large-scale brain networks (e.g., the default mode network and a comprehensive attention-networked system), leading to a heterogeneous presentation of clinically assessed outcomes. The outcomes include psychogenic paralysis of limbs, left-side neglect, rectified sense of other locations, disorders of consciousness, symptoms related to autism spectrum disorder, Alzheimer's disease, schizophrenia, and depersonalization/derealization disorder. By consolidating evidence from neuroimaging, lesion-symptom mapping, and computational assessment, we aim to reconceptualize these disorders not as separate and independent maladies, but as manifestations of a deeper, shared etiology, supporting a network-based assessment strategy for diagnosis and treatment that seeks to restore self-in-space.},
}

@article {pmid41531872,
year = {2025},
author = {Cheng, W and Wang, M and Zhou, C and Li, M},
title = {Exploring the link trend in the field of coronaviruses and cognitive impairment: A bibliometric analysis based on bibliometrix.},
journal = {Brain circulation},
volume = {11},
number = {4},
pages = {322-332},
doi = {10.4103/bc.bc_107_24},
pmid = {41531872},
issn = {2455-4626},
abstract = {BACKGROUND: Coronaviruses (CoVs) significantly impact human health, targeting the respiratory and nervous systems and causing long-term complications such as cognitive impairment. While the cognitive effects of CoVs, including severe acute respiratory syndrome CoV, are well-documented, a comprehensive analysis of the evolving research landscape remains unexplored.

METHODS: We performed a bibliometric analysis of CoV-related cognitive research from 1998 to 2025 using data from the Web of Science Core Collection. Bibliometrix software was employed to examine publication trends, geographical contributions, institutional output, author collaborations, and research hotspots.

RESULTS: Among 4,076 publications analyzed, a dramatic rise in research output was observed post-2020, correlating with the COVID-19 pandemic. The United States led in publication count (24.63%) and citations, followed by Italy and China. The University of Toronto is ranked as the most prolific institution. The most highly cited articles are from Alzheimer's and Dementia, The Lancet Infectious Diseases, and eClinicalMedicine. Cao Bing, Mazza, Mario Gennaro, and Wang Yi had the most influence on CoV impact on cognitive impairment. Keyword analysis revealed emerging research themes such as "depression," "anxiety," and "health," reflecting the psychological and cognitive effects of the pandemic. Highly cited articles identified neuroinflammatory and neuroimmune pathways, emphasizing the role of viral invasion in cognitive dysfunction.

CONCLUSION: The COVID-19 pandemic has driven a surge in studies linking CoV infections to cognitive impairment. This research highlights mechanisms such as blood-brain barrier disruption, neuronal damage, and altered cerebral glucose metabolism. Future studies should focus on standardized diagnostic criteria and therapeutic strategies to mitigate long-term cognitive sequelae.},
}

@article {pmid41531784,
year = {2025},
author = {Zhang, Y and Ren, Y and Zhu, X and Liu, T and Han, R and Fang, Y and Zhao, Z and Mao, F and Wang, Y and Li, X and Li, X},
title = {Research Progress on Idebenone in Neurodegenerative Diseases.},
journal = {Aging medicine (Milton (N.S.W))},
volume = {8},
number = {6},
pages = {624-633},
doi = {10.1002/agm2.70047},
pmid = {41531784},
issn = {2475-0360},
abstract = {In recent years, significant progress has been made in understanding the therapeutic potential of idebenone (IDE), a synthetic analogue of Coenzyme Q10, in neurodegenerative diseases (NDs). This review comprehensively examines the pharmacological properties of IDE and its emerging applications in various NDs, with particular emphasis on Alzheimer's disease, Parkinson's disease, Friedreich's ataxia, and Huntington's disease. We elucidate IDE's multifaceted neuroprotective mechanisms, including its potent antioxidant activity that reduces reactive oxygen species production, its ability to enhance mitochondrial bioenergetics, and its regulatory effects on cellular metabolism. Additionally, we critically evaluate current clinical research findings and discuss the translational potential of IDE in ND therapeutics. The accumulated evidence strongly supports IDE as a promising mitochondrial-targeted agent capable of mitigating disease symptoms and modifying disease progression in multiple neurodegenerative disorders. This review highlights both the current achievements and future directions for IDE-based interventions in ND treatment.},
}

@article {pmid41531657,
year = {2025},
author = {Subali, D and Kurnia, G and Yanti, Y and Christos, RE and Shih, YC},
title = {Unveiling Neuroprotective Potential in Tempeh Peptide Extracts by In Vitro Screening of Anti-Alzheimer's Compounds.},
journal = {Reports of biochemistry & molecular biology},
volume = {14},
number = {1},
pages = {46-56},
doi = {10.61882/rbmb.14.1.46},
pmid = {41531657},
issn = {2322-3480},
abstract = {BACKGROUND: Alzheimer's Disease (AD) incidence and prevalence increase every year, commonly related to neuron inflammation and degeneration conditions. Tempeh, a traditional fermented product from Indonesia, was reported to have anti-inflammatory, antioxidant, and anti-Alzheimer properties. However, anti-Alzheimer properties of tempeh peptide extracts have not been extensively examined. This research studied the effect of the extracted peptide from tempeh in preventing and delaying Alzheimer's disease.

METHODS: Tempeh peptide was extracted using water maceration and quantified using HPLC and spectrophotometry. Anti-Alzheimer properties of tempeh were analyzed with Ellman's assay of anticholinesterase and in vitro gene expression analysis using LPS-induced neural Schwann cells.

RESULTS: As a result, tempeh contained 19.27% of GABA, which is reported to have anti-Alzheimer properties, and other amino acids. Tempeh peptide extract at 12.5 µg/mL had strong inhibition activity toward acetylcholinesterase at 12.61%, and 100 µg/mL of tempeh peptide extract had 8.97% butyrylcholinesterase inhibition activity. Tempeh peptides extract also altered the expression of various genes related to Alzheimer's disease, such as TNF-α, BACE 1, Ntrk 1, BDNF 2, and APP.

CONCLUSIONS: This research proved that various peptides from tempeh have anti-Alzheimer properties.},
}

@article {pmid41531586,
year = {2025},
author = {Kwapien, E and Piszka, M and Czarnecki, F and Mesyasz, M and Owczarska, A and Dacyl, H and Banach, J and Kasprzyk, WZ and Luczak, JK and Bartkowski, J},
title = {Habitual Coffee Consumption and Systemic Health Outcomes: A Comprehensive Review.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99094},
doi = {10.7759/cureus.99094},
pmid = {41531586},
issn = {2168-8184},
abstract = {This review analyzes extensive scientific data linking habitual coffee consumption to a wide range of physiological outcomes and divides them into cardiovascular, metabolic, and organ-specific effects. Unlike previous assumptions, moderate coffee intake positively affects many aspects of the health of the adult population. We can observe beneficial effects that translate into patients' longevity as well as reduced risks of chronic diseases. After analyzing the studies, the most significant protective associations were identified in the cardiovascular system, where moderate consumption (three to four cups daily, corresponding to approximately 450-600 mL of coffee) correlates with reduced all-cause and cardiovascular mortality, and a lower risk of heart failure. Many studies have highlighted the chemo-preventive potential of coffee constituents, indicating a reduced risk of specific malignancies, including liver and prostate cancer. The health consequences that manifest themselves clinically also include improved metabolic homeostasis, specifically a lower incidence of type 2 diabetes mellitus and liver fibrosis. This impact also extends to the central nervous system, where there is a clear correlation between caffeine intake and neuroprotection against neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Evidence indicates a "J-shaped" relationship in many cases, suggesting that moderate intake is optimal. Conversely, supraphysiological consumption can induce transient hemodynamic disturbances, and unfiltered preparations may negatively impact lipid profiles due to higher diterpene content. Furthermore, evidence supports a linear dose-response relationship between caffeine intake and adverse pregnancy outcomes, specifically pregnancy loss, highlighting the need for strict caution in prenatal care. Due to the proven bioactive properties of compounds like chlorogenic acid and caffeine, updated public health perspectives are needed to recognize coffee not merely as a stimulant, but as a functional dietary component that promotes a healthy lifestyle, which will translate into the reduced burden of non-communicable diseases in the future.},
}

@article {pmid41531526,
year = {2026},
author = {Muzychka, LV and Muzychka, OV and Kobzar, OL and Vovk, AI and Smolii, OB},
title = {Design, synthesis and evaluation of new pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidines as tacrine-like acetylcholinesterase inhibitors.},
journal = {RSC advances},
volume = {16},
number = {3},
pages = {2417-2427},
doi = {10.1039/d5ra06700f},
pmid = {41531526},
issn = {2046-2069},
abstract = {The development of acetylcholinesterase (AChE) inhibitors remains a promising research direction in drug discovery for Alzheimer's disease. A series of eighteen pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized as novel tacrine-like AChE inhibitors. Sixteen compounds inhibited AChE in the micromolar range. Among them, 4-(dimethylamino)-7,8-dimethylpyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin-6(7H)-one (22) exhibited the highest inhibitory activity against the enzyme with an IC50 value of 0.22 ± 0.02 µM, showing mixed-type inhibition. In silico studies showed that 22 occupies the catalytic anionic site of hAChE and forms strong π-π stacking interactions with Trp86, similar to those of tacrine. This study demonstrates the potential use of methyl-substituted pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidines in the development of potent AChE inhibitors.},
}

@article {pmid41531459,
year = {2025},
author = {Fischer, BL and Van Hulle, CA and Norton, DL and Wyman, MF and Ennis, G and Lambrou, NH and Bouges, S and Gooding, DC and Gleason, CE},
title = {Mild Behavioral Impairment is Associated With Incident Cognitive Decline Among Dementia-Free, Racially Diverse Older Adults: Data From the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) Study.},
journal = {The American journal of geriatric psychiatry. Open science, education, and practice},
volume = {8},
number = {},
pages = {43-53},
doi = {10.1016/j.osep.2025.09.002},
pmid = {41531459},
issn = {2950-3868},
abstract = {OBJECTIVES: To determine whether MBI associates with worse cognitive performance over time and with incident cognitive decline in an older, racially/ethnically diverse cohort at early stages of cognitive change.

DESIGN: This observational cohort study followed participants from the Wisconsin Alzheimer's Disease Research Center Clinical Core (WADRC) for up to 13 visits.

SETTING: An urban university research center.

PARTICIPANTS: Participants from the WADRC Clinical Core were included in this convenience sample if they were without dementia, had undergone at least 1 cognitive assessment, and completed measures of cognitive, clinical and affective function.

MEASUREMENTS: MBI was assessed using the Neuropsychiatric Inventory. Linear mixed effects models (LME) were fit to cognitive outcomes Trailmaking Tests A and B (TMT-A, B) and Wechsler Logical Memory (LM). Cox proportional hazard models assessed whether MBI was related to risk for incident global Clinical Dementia Rating Scale (CDR >0).

RESULTS: N = 584 participants with mean age 64.6 years, range 46-92.6 years, 59.4% female and 17% African American. LME results indicated participants with MBI exhibited worse age-associated decline on TMT-B, compared to those without MBI (beta=0.008, p = 0.01, CI: 0.002, 0.01, t(337) = 2.4, p = 0.01). MBI at baseline was associated with a significant hazard ratio (HR) indicating an increased risk of decline on the CDR (HR: 2.84; HR 95% CI: 1.68 - 4.81; p = 0.0001).

CONCLUSIONS: MBI associated with worse cognitive performance and incident cognitive decline in a racially diverse, older adult sample at early stages of cognitive change. Increased awareness of the late life emergence of neuropsychiatric symptoms is warranted to assist in identification and improve prognostication and treatment of neurodegenerative disease.},
}

@article {pmid41531227,
year = {2026},
author = {Samudra, N and Vemuri, M and Weitlauf, J},
title = {Menopause, cognition, and Alzheimer's disease risk.},
journal = {Current opinion in obstetrics & gynecology},
volume = {},
number = {},
pages = {},
doi = {10.1097/GCO.0000000000001087},
pmid = {41531227},
issn = {1473-656X},
abstract = {PURPOSE OF REVIEW: Cognitive symptoms are common throughout the menopause transition. This review outlines a comprehensive clinical approach, grounded in recent findings, to guide clinicians in addressing menopause-related cognitive concerns and neurodegenerative disease risk for midlife women.

RECENT FINDINGS: Research highlights the benefits of lifestyle and psychosocial interventions for cognitive symptoms during the menopause transition. Addressing underlying medical and mental health conditions, as well as difficulties with sleep, chronic stress, and vasomotor symptoms, can ameliorate symptoms and reduce risk for future dementia. Cognitive changes during the menopause transition do not typically indicate dementia. A subset of women, including apolipoprotein ε4 (APOE ε4) carriers and those who experience early menopause, face heightened risk. Alzheimer's disease biomarkers are clinically available and may change in some women during the menopause transition, particularly in APOE ε4 carriers, but our understanding of these changes, as well as their relationship to menopause hormone therapy, is evolving. There is presently insufficient evidence for the role of menopause hormone therapy for the treatment of menopause-related cognitive symptoms or neurodegenerative disease prevention.

SUMMARY: While typically transient, cognitive symptoms in menopause can benefit from addressing comorbid medical and psychosocial conditions. Research into dementia risk related to changes in the menopause transition is ongoing.},
}

@article {pmid41531182,
year = {2026},
author = {Hamilton, CA and Gallagher, P and Donaghy, PC and Ciafone, J and Firbank, M and Greenfinch, G and Heslegrave, A and Zetterberg, H and Taylor, JP and Allan, LM and O'Brien, JT and Thomas, AJ},
title = {Subjective estimation of cognitive function in mild cognitive impairment: relationship with neurodegenerative and non-degenerative factors.},
journal = {Psychological medicine},
volume = {56},
number = {},
pages = {e19},
doi = {10.1017/S0033291725102997},
pmid = {41531182},
issn = {1469-8978},
support = {//GE Healthcare/ ; //Alzheimer's Research Trust/ ; //NIHR Newcastle Biomedical Research Centre/ ; //National Institute for Health Research Applied Research Collaboration South West Peninsula/ ; //NIHR Cambridge Biomedical Research Centre/ ; //Cambridge Centre for Parkinson-Plus/ ; //Dementias Platform UK/ ; //UCLH Biomedical Research Centre/ ; UKDRI-1003//UK Dementia Research Institute/ ; },
mesh = {Humans ; *Cognitive Dysfunction/psychology/physiopathology/diagnosis/pathology ; Male ; Female ; Aged ; *Alzheimer Disease/psychology/physiopathology ; Aged, 80 and over ; Hippocampus/pathology ; *Metacognition/physiology ; Depression/psychology ; Atrophy ; Middle Aged ; *Lewy Body Disease/psychology/physiopathology ; Neuropsychological Tests ; *Cognition ; },
abstract = {BACKGROUND: Subjective cognitive complaints are poor predictors of neurodegenerative disease and future dementia. Errors in metacognition, positive or negative differences between actual and perceived performance, may partially explain this. We aimed to assess whether hypothesized indicators of underlying neurodegenerative factors (e.g. hippocampal atrophy) in mild cognitive impairment (MCI) were associated with overestimation of actual cognitive performance, and hypothesized non-degenerative factors (e.g. depression) were associated with underestimation of performance.

METHODS: Metacognitive error was estimated from paired subjective and objective cognitive assessments using the Multifactorial Memory Questionnaire and Addenbrooke's Cognitive Examination - Revised, respectively. A normative model was developed with cognitively healthy older adults (n = 36), and applied to individuals with suspected MCI due to Alzheimer's disease (AD) or MCI with Lewy bodies (total n = 88). Theorized predictors of subjective overestimation or underestimation of performance (metacognitive error) were assessed, including demographics, AD biomarkers, and mental and physical ill health. Metacognitive error was also assessed as a predictor of conversion to dementia.

RESULTS: Underestimation of cognitive function was associated with depressive symptoms, anxiety, and self-reported autonomic symptoms. Overestimation of cognitive function was associated with age, hippocampal atrophy, plasma glial fibrillary acidic protein, and subsequent dementia conversion.

CONCLUSIONS: Underestimation of cognitive function may reflect functional cognitive changes linked to mental and physical ill health, while overestimation of function may be a marker of neurodegenerative changes. Quantifying metacognitive error may provide a noninvasive screening tool for progressive MCI, requiring investigation in an independent sample.},
}

Humans
*Cognitive Dysfunction/psychology/physiopathology/diagnosis/pathology
Male
Female
Aged
*Alzheimer Disease/psychology/physiopathology
Aged, 80 and over
Hippocampus/pathology
*Metacognition/physiology
Depression/psychology
Atrophy
Middle Aged
*Lewy Body Disease/psychology/physiopathology
Neuropsychological Tests
*Cognition

@article {pmid41530979,
year = {2026},
author = {Thornton, JM and Stevenson, JL},
title = {Mites, microbes, and neurodegeneration: A unified environmental hypothesis for Parkinson's disease, Alzheimer's disease, and Lewy body dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251412923},
doi = {10.1177/13872877251412923},
pmid = {41530979},
issn = {1875-8908},
abstract = {Emerging evidence suggests that various microbes and mites may play a significant role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD). The association between microbial exposure and these conditions raises the possibility that mites, as vectors or direct agents, could contribute to disease onset and progression. PD, with 15% or less of cases linked to genetics, highlights the importance of environmental factors in the remaining sporadic cases. Mites, known to harbor prions, suggest a potential mechanism for horizontal transmission. Mites can inject neurotoxins that may disrupt neurological systems, potentially leading to movement disorders, memory loss, and cognitive decline. Conditions like seborrheic dermatitis and rosacea, linked to mites such as Demodex, are highly prevalent in patients with PD and AD, and mite-induced inflammation may exacerbate disease symptoms. Mite infestations can cause systemic illness, including respiratory, gastrointestinal, and neurological disturbances. Due to their microscopic size, they are often undetected and potentially can swap DNA with humans. This article summarizes observations linking mite exposure to neurodegenerative diseases. In one family, a member was diagnosed with LBD following chronic skin issues and mite exposure, while another developed symptoms associated with PD. Mites may contribute through prion transmission, neurotoxin injection, or by triggering inflammation. A nationwide study found that scabies patients treated with lindane, a neurotoxic pesticide, had a significantly reduced PD risk, suggesting a protective effect. These findings underscore the urgent need for further research into mites and environmental triggers.},
}

@article {pmid41530968,
year = {2026},
author = {Yuan, J and Hu, Y and Feng, F and Hou, B and You, H and Yang, J and Zhou, Y and Hao, H and Wang, C and Zhang, W and Jiao, J and Wang, L and He, J and Xiao, W and Gao, P and Qu, Q and Lü, Y and Ye, Q and Wang, Q and Wang, Y and Liu, C and Chen, W and Yuan, Y and Cui, R and Qiao, H and Liu, S and Sha, L and Liu, H and Ge, F and Li, L and An, N and Shan, G and Chan, P and Zhang, J and Zuo, Z and Libon, DJ and Li, Y and Cui, L and Wang, Y and Zhou, J and Chen, W and Xu, Q and Román, GC and Zhang, ZX},
title = {Prevalence of subjective cognitive decline with Alzheimer's disease neuropathology in a community-based Chinese cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411413},
doi = {10.1177/13872877251411413},
pmid = {41530968},
issn = {1875-8908},
abstract = {BackgroundEarly detection of Alzheimer's disease (AD) is critical for timely intervention. Subjective cognitive decline (SCD), defined as self-perceived cognitive worsening while objective performance on standardized tests remains normal, when accompanied by neurodegenerative changes on brain imaging (e.g., hippocampal atrophy), can be classified as SCD with neurodegeneration of AD form (SCD-NDAD). This phenotype may represent an early stage of AD.ObjectiveInvestigate the prevalence and clinical characteristics of SCD-NDAD in general population.Methods: This multicenter, community-based cross-sectional study was conducted from 2013 to 2019 across 31 communities in eight major cities of northern, eastern, southern, and western China. Community-dwelling adults aged 50 years and older were recruited through cluster sampling. Participants underwent standardized interviews, neuropsychological assessments, and magnetic resonance imaging, on the basis of which SCD-NDAD was identified. The prevalence of SCD-NDAD was estimated with age- and sex-standardized weights.ResultsOf 5054 participants (mean age 69.4 years, 60.6% women), 2886 completed MRI. In participants aged ≥50 years, the prevalence of SCD-NDAD was 4.9% (95% confidence interval: 4.1% to 5.8%). In participants aged 65 years and older, prevalence increased to 6.5% (95% confidence interval: 5.5% to 7.7%). While these individuals exhibited preserved cognitive function across all domains, they demonstrated significant hippocampal atrophy, a key marker of AD-related neurodegeneration.ConclusionsSCD-NDAD is common among older adults in China, with an estimated prevalence affecting 12.4 million individuals aged ≥65 years. Identifying this cohort may offer a critical window for early intervention and holds significant implications for public health strategies aimed at dementia prevention.},
}

@article {pmid41530949,
year = {2026},
author = {Chen, Y and Liu, Y},
title = {Eosinophils: Pathological Mechanisms and Novel Targeted Therapeutic Strategies Across Multiple Disease Spectrums.},
journal = {Journal of leukocyte biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jleuko/qiag009},
pmid = {41530949},
issn = {1938-3673},
abstract = {Eosinophils are a type of white blood cell belonging to the granulocyte family. Their cytoplasm contains eosinophilic granules that hold various biologically active substances. They perform diverse functions, participating in inflammatory responses, immune defense, and tissue repair. Eosinophils are implicated in the pathogenesis of multiple diseases, including infectious diseases, allergic disorders, and hematological conditions. Moreover, increasing research in recent years has revealed significant associations between eosinophils and autoimmune diseases, solid tumors, coronary atherosclerotic heart disease, and even Alzheimer's disease. They participate in disease onset and progression through the release of toxic proteins, cytokines, and chemokines, as well as through interactions with other cells. Focusing on the biological characteristics and functions of eosinophils facilitates the elucidation of disease mechanisms associated with related disorders. This, in turn, provides further direction for eosinophil-targeted research and therapeutic strategies, including the research and development of drugs that modulate their function, targeted therapies, immunotherapies, and cell therapies. This paper provides a comprehensive review of the structure, function, and role of eosinophils in related diseases, along with potential future therapeutic strategies. It aims to deepen the understanding of researchers and clinicians, thereby facilitating their application in further research, as well as in clinical disease diagnosis and treatment analysis.},
}

@article {pmid41530948,
year = {2026},
author = {Andin, U and Lifvergren, S and Zetterberg, H and Blennow, K and Lundin, R and Svensson, J},
title = {Cerebrospinal fluid levels of neurogranin and YKL-40 in mild cognitive impairment due to Alzheimer's disease or vascular dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411336},
doi = {10.1177/13872877251411336},
pmid = {41530948},
issn = {1875-8908},
abstract = {BackgroundMarkers of synaptic degeneration and neuroinflammation have been investigated in memory clinic cohorts, but less is known about their role in community-dwelling subjects.ObjectiveTo investigate baseline cerebrospinal fluid (CSF) levels of neurogranin and YKL-40 in community-dwelling subjects with mild cognitive impairment (MCI) who had not yet sought help for their cognitive decline.MethodsWe recruited and characterized 107 subjects, who at the clinical baseline examination were found to have MCI. Based on the clinical progression at a 3-year follow-up, the individuals were classified as MCI-Alzheimer's disease (MCI-AD, n = 40), MCI-vascular dementia (MCI-VaD, n = 25), and stable MCI (sMCI, n = 42).ResultsBaseline CSF neurogranin level was elevated in the MCI-AD group compared with the MCI-VaD and sMCI groups (p = 0.02 and p < 0.001, respectively), and baseline CSF YKL-40 level was higher in the MCI-AD group than in the sMCI group (p = 0.01). Neurogranin, and to a lesser extent YKL-40, correlated positively with CSF levels of total tau and phosphorylated tau181 in all study groups. However, in receiver operator characteristics analyses, neurogranin and YKL-40 used alone or in combination had a moderate diagnostic accuracy that was lower than that of the core AD biomarkers (amyloid-β42, total tau, and phosphorylated tau181).ConclusionsThis study shows that neurogranin and YKL-40 in CSF are elevated in MCI-AD compared with sMCI, and neurogranin was also higher in MCI-AD than in MCI-VaD. Neurogranin and YKL-40 had a moderate diagnostic accuracy, but they could still be of value to characterize the clinical consequences of postsynaptic dysfunction and neuroinflammation.},
}

@article {pmid41530860,
year = {2026},
author = {Li, J and Li, A and Ye, C and Zhang, L and Jiang, M and Lan, G and Gonzalez-Ortiz, F and Yang, J and Zhu, Y and Cai, Y and Sun, P and Liu, L and He, Z and Zhou, X and Fang, L and Wang, Y and Liu, Z and Blennow, K and Ma, S and Chen, X and Shi, D and Guo, T},
title = {Plasma platelet-derived growth factor receptor-β decrease correlates with blood-brain barrier damage in Alzheimer's disease.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00926-4},
pmid = {41530860},
issn = {1750-1326},
support = {RCYX20221008092935096//Shenzhen Science and Technology Innovation Program/ ; 82422027//National Natural Science Foundation of China/ ; 2023B1515020113//Guangdong Basic and Applied Basic Science Foundation/ ; S241101004-1//Shenzhen Bay Laboratory/ ; LGL-3142-ADB510200//Lingang Laboratory/ ; },
}

@article {pmid41350755,
year = {2025},
author = {Duggan, MR and Sipilä, PN and Yang, Z and Wen, J and Erus, G and Bilgel, M and Lewis, A and Moghekar, A and Davatzikos, C and Resnick, SM and Kivimäki, M and Walker, KA},
title = {Post-infection brain atrophy accelerates cognitive and molecular changes underlying dementia.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {8},
pmid = {41350755},
issn = {1758-9193},
abstract = {BACKGROUND: Infections have been associated with a greater risk of Alzheimer’s disease and related dementias (ADRD), but it is unclear how infections influence structural brain patterns over time, and whether post-infection brain atrophy can accelerate cognitive decline and molecular changes underlying dementia.

METHODS: Using the Baltimore Longitudinal Study of Aging (BLSA; n = 793; mean age = 70.1), we examined how infections relate to longitudinal changes in machine learning-derived, 3 T-MRI neuroimaging signatures, and leveraged the UK Biobank (UKB; 1,120; mean age = 62.9 yrs) to externally validate infection-brain atrophy relationships. Using the BLSA, we also asked if infection history and infection-related brain volume loss were associated with cognitive decline, amyloid-beta PET, and ADRD plasma biomarker trajectories (Aβ42/40, pTau-181, NfL, GFAP).

RESULTS: We detected accelerated parieto-temporal atrophy in BLSA participants with a history of upper respiratory tract, bacterial, and urinary tract infections (p < 0.05), as well as influenza and skin/subcutaneous infections (FDR p < 0.05). After demonstrating their associations with longitudinal neuroimaging signatures in the UKB and prevalent dementia in the BLSA, we found that infections were related to a greater burden of ADRD plasma biomarkers and accelerated rates of cognitive decline in BLSA participants. Integrating longitudinal brain scans, cognitive assessments, and plasma biomarker measurements, we identified infection-related changes in verbal memory and NfL that were more prominent among BLSA participants who experienced greater post-infection brain atrophy.

CONCLUSION: Along with demonstrating that infections mediate clinically relevant brain atrophy patterns, these findings highlight the consequences of post-infection brain volume loss on longitudinal neurocognitive outcomes and extend our understanding of the biological basis by which infections may contribute to neurodegeneration.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-025-01924-2.},
}

@article {pmid41345575,
year = {2025},
author = {Turner, SG and Brody, L and Mei, L and Figueroa-Nieves, A and Smiley, A and Reid, MC and Herr, K and Sacerio, L and Moxley, J and Pillemer, K and Riffin, C},
title = {The pain identification and communication toolkit: a training program to support family caregivers of persons with ADRD.},
journal = {BMC geriatrics},
volume = {26},
number = {1},
pages = {31},
pmid = {41345575},
issn = {1471-2318},
support = {T32 AG049666/AG/NIA NIH HHS/United States ; K01 AG061275/AG/NIA NIH HHS/United States ; T32 AG049666/AG/NIA NIH HHS/United States ; T32 AG049666/AG/NIA NIH HHS/United States ; T32 AG049666/AG/NIA NIH HHS/United States ; K01 AG061275/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Pain is highly prevalent, yet under-detected and under-managed, in older persons with Alzheimer’s Disease and Related Dementias (ADRD). ADRD family caregivers are well situated to facilitate timely identification and management of pain symptoms in their care recipients, but lack knowledge and training in these areas. This paper describes the protocol for a randomized controlled trial evaluating the efficacy of the Pain Identification Communication Toolkit (PICT), a multicomponent intervention designed to enhance caregivers’ abilities to recognize pain symptoms and communicate those symptoms to health care providers.

METHODS: The trial uses a two-group parallel design in which caregiving dyads (older adults with comorbid diagnoses of ADRD and pain and their family caregiver) are randomized to PICT or a control condition. Target enrollment is 220 dyads. Caregivers in both study arms complete four weekly sessions (time to completion ranges from 30 to 60 min) delivered by a trained interventionist. In the PICT sessions caregivers receive training on observational pain assessment and effective techniques for communicating pain symptoms to healthcare providers. The comparison group controls for time and attention and focuses on health-related topics, such as sleep, exercise, and nutrition. Caregivers complete assessments at baseline (pre-intervention), post-intervention (1-month), and follow-up (3-months and 6-months after intervention completion). Older adults’ sociodemographic and health characteristics are abstracted from their electronic health record (EHR) at the same timepoints. Primary outcomes are caregivers’ recognition and communication of pain. Secondary outcomes include older adult’s pain treatments and behavioral disturbance, and caregiver distress and burden. Caregivers’ self-efficacy in pain recognition and communication is evaluated as a putative mechanism of action.

DISCUSSION: PICT is the first intervention to train family caregivers of community-dwelling older adults with ADRD in pain symptom recognition and communication. The trial will evaluate PICT’s efficacy and provide crucial data regarding its mechanisms of action, laying the foundation for future refinement and implementation in real world care delivery.

TRIAL REGISTRATION: The clinical trial is registered at ClinicalTrials.gov under NCT06168604 (December 12, 2023).

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-025-06717-8.},
}

@article {pmid41532026,
year = {2024},
author = {Yu, HN and He, J and Kim, B and Ying, GS},
title = {Association between diabetic retinopathy and neurodegenerative diseases in the All of Us research program.},
journal = {AJO international},
volume = {2},
number = {4},
pages = {},
doi = {10.1016/j.ajoint.2025.100190},
pmid = {41532026},
issn = {2950-2535},
abstract = {PURPOSE: While diabetic retinopathy (DR) has previously been linked to neurodegenerative diseases, it remains unclear whether DR independently reflects neurodegenerative diseases beyond those attributable to diabetes itself. In this study, we leveraged data from the All of Us Research Program to assess whether DR serves as an independent marker of neurodegenerative disease among individuals with diabetes.

METHODS: A matched case-control, cross-sectional study was conducted using data from the All of Us Research Program (US-based EHR database). Three groups (exactly matched by age, sex, and race) were created and compared: individuals with both DR and DM (DR+DM, n = 7629), individuals with DM but no DR (DM-only, n = 22,887), and individuals without DM (n = 22,887). Outcomes included dementia, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Univariate and multivariate logistic regression analyses were performed, adjusting for demographics, comorbidities and diabetes-related mediators.

RESULTS: In multivariable analysis, DM-only was associated with increased odds of dementia (adjusted odds ratio [aOR] 1.28, 95 % CI: 1.08-1.51; p = 0.004). However, DR in the setting of DM (DM+DR vs. DM-only) was not associated with further increased odds of neurodegenerative disease outcome in multivariate models (aOR for dementia 1.18, 95 % CI: 0.94-1.49). No significant associations were identified for AD, PD, or MS (all p ≥ 0.10).

CONCLUSION: Diabetic retinopathy was not associated with increased rates of neurodegenerative diseases beyond that conferred by diabetes itself, and the relationship may be mediated by diabetes severity and related comorbidities.},
}

@article {pmid41530554,
year = {2026},
author = {Taylor, WD and Gerlach, AR and Szymkowicz, SM and Gujral, S and Andreescu, C},
title = {Remission is insufficient: predictors and mechanistic models of recurrence in late-life depression.},
journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41530554},
issn = {1740-634X},
support = {R01 MH121620/MH/NIMH NIH HHS/United States ; R01 MH123662/MH/NIMH NIH HHS/United States ; R33 MH122464/MH/NIMH NIH HHS/United States ; K01 MH133913/MH/NIMH NIH HHS/United States ; K23 MH125074/MH/NIMH NIH HHS/United States ; R01 MH108509/MH/NIMH NIH HHS/United States ; R01 MH121619/MH/NIMH NIH HHS/United States ; },
abstract = {While achieving remission is the goal of acute antidepressant treatment, recurrence of new depressive episodes following remission is unfortunately common in clinical populations with Major Depressive Disorder, including older adults with Late-Life Depression (LLD). The neurobiological factors underlying this risk are poorly understood, limiting our ability to identify potential preventive mechanistic targets. Beyond the limited prognostic utility achieved from individual psychiatric history, it remains challenging to clinically stratify individual risk. This review examines factors influencing the recurrence of depressive episodes following remission in LLD, focusing on cognitive, behavioral, social, and environmental aspects. It additionally considers neuroimaging-based biomarkers related to recurrence risk as well as discussing evidence for and limits of maintenance treatment to prevent recurrence. The paper proposes possible mechanisms contributing to recurrence, including physiological and behavioral responses to stressors, the influence of Alzheimer's disease neuropathology, and conceptualizing repeat depressive episodes within the accelerated aging hypothesis of LLD. A dynamical landscape model of depression recurrence is proposed to elucidate the interplay between different mood states, resilience, and treatment response. This synthesis then highlights avenues for future research, focusing on areas of potential significance ranging from risk stratification to tertiary prevention efforts that may improve both long-term affective and cognitive symptoms.},
}

@article {pmid41530426,
year = {2026},
author = {Huijbers, W and Wischmann, HA and Gruber, J and Pistoia, K and Krieger, J and Gillies, M and Nasreddine, Z},
title = {Real-world evidence from 50,000 online participants using MoCA-XpressO for cognitive prescreening.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35640-0},
pmid = {41530426},
issn = {2045-2322},
abstract = {XpressO is a digital cognitive prescreening tool developed by Montreal Cognition (MoCA Test Inc.). In this study, we evaluated real-world online data collected through XpressO in 2024 and early 2025, based on over 50,000 self-enrolled online participants. In line with expectations, we found that the XpressO score-which predicts screening positive for (mild) cognitive impairment-is associated with sex, age, and education. The results indicated that women have a 5.8% [5.3%, 6.3%] lower relative risk of prescreening positive for cognitive impairment, each additional year of age increases the relative risk by 0.59% [0.57%, 0.60%], whereas each year of education decreases the relative risk by 0.99% [0.94%, 1.06%]. We also visualized and quantified interaction effects among these demographic variables as predictors of the XpressO score. While the interaction effect between sex and age was not statistically significant, all other interaction terms, including the three-way interaction between sex, age, and education, were significantly associated with the XpressO score. Additionally, adjusting for demographic factors reduced the observed effect of potential confounders, the language and the platform used. However, when we evaluated a score adjusted for demographics in a clinical cohort of 101 participants, we found that this adjustment slightly but significantly reduced the discriminatory power of the XpressO tool in identifying individuals with cognitive impairment from 0.86 to 0.81. These findings from a real-world online cohort offer novel insights into the complex influence of demographic factors on digital cognitive prescreening. Moreover, they demonstrate that XpressO is a viable tool for online prescreening and can help streamline the diagnostic pathway for individuals who may be eligible for disease-modifying treatments for Alzheimer's disease.},
}

@article {pmid41530008,
year = {2026},
author = {Feldman, OJ and Herrmann, N and Ruthirakuhan, M and Gallagher, D and L G Verhoeff, NP and Kiss, A and Black, SE and Lanctôt, KL},
title = {Assessment of clinical factors that predict response to nabilone for agitation in Alzheimer's disease: A post hoc analysis of a randomized placebo-controlled trial.},
journal = {International psychogeriatrics},
volume = {},
number = {},
pages = {100183},
doi = {10.1016/j.inpsyc.2026.100183},
pmid = {41530008},
issn = {1741-203X},
abstract = {INTRODUCTION: Previously, nabilone showed a medium effect size for treating agitation in moderate-to-severe Alzheimer's disease (AD), but response varied. These post hoc analyses aimed to identify a group of clinical characteristics that predicted treatment response.

METHODS: Data from a double-blind, placebo-controlled crossover trial in AD agitation were used. Nineteen clinical characteristics were categorized (presence/absence) and evaluated for relation to agitation response (change on Cohen-Mansfield Agitation Inventory (CMAI)). Characteristics with a ≥ 8 point response difference between categories were included in a multivariable analysis model to calculate individual predicted response. Linear mixed-effects models with Satterthwaite's approximation evaluated the impact of treatment on the relationship between predicted and observed responses.

RESULTS: Thirty-nine participants (77 % male, mean [SD] age 87 [10.2], standardized Mini-Mental State Exam (sMMSE) 6.5 [6.8]) were enrolled. Variable selection identified five characteristics related to greater nabilone efficacy: higher pain (Pain Assessment in Advanced Dementia score ≥3) (difference [SE] in CMAI response = -18.8 [3.2]), greater appetite and eating disorders (-16.4 [5.5]), greater apathy (-14.0 [5.5]), less cognitive impairment (sMMSE greater than 10) (-16.5 [4.2]) and no concomitant cholinesterase inhibitors (-13.9 [4.4]). For those with a predicted response in the top tertile based on those five characteristics, 82 % responded, compared with 40 % in the lowest tertile. A treatment-by-tertile interaction (F(2,29) = 8.48, p = 0.001) indicated observed treatment response varied across tertiles.

CONCLUSION: A reliable clinical profile of persons with AD related agitation likely to respond to nabilone may be established with additional research.},
}

@article {pmid41529928,
year = {2026},
author = {Honda, M and Yamada, T and Watanabe, S and Watanabe, A and Nagaoka, T and Nemoto, M and Mikami, K and Hanaoka, K and Kaida, H and Handa, H and Ishii, K and Kimura, Y},
title = {Synthesis of Amyloid Images Using a Generative Adversarial Network from 2-Dimensional [18]F-FDG Images and Evaluation for Clinical Use.},
journal = {Journal of nuclear medicine technology},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnmt.125.270154},
pmid = {41529928},
issn = {1535-5675},
abstract = {The use of amyloid PET to assess patient suitability of disease-modifying drugs for Alzheimer disease is increasing. This study aimed to synthesize amyloid PET images from [18]F-FDG PET images using a generative artificial intelligence algorithm to reduce unnecessary amyloid PET scans. Methods: A 2-dimensional pix2pix algorithm was used. The algorithm was evaluated across 4 domains: image quality, voxel values, contrast between white and gray matter, and diagnostic performance for detecting the presence or absence of β-amyloid (Aβ) deposition. Pairs of [18]F-FDG PET and amyloid PET images from 55 Aβ-negative and -positive cases were evaluated. A 6-fold cross-validation was conducted. Results: Synthetic images were visually consistent, producing plausible negative and positive patterns while preserving continuity in the sagittal plane. Voxel values of the synthetic images showed a significant linear relationship with the real images. The contrast correlated well with the real images, and the differences between the negative and positive cases were significant as well as those in the real images. The performance of the positive or negative 2-class classifier exceeded 85% for the synthetic images. Conclusion: The synthetic images successfully captured features of Aβ deposition, and evaluation with a 2-class classifier achieved an acceptable accuracy of 85%. These results suggest that amyloid images can potentially be generated from [18]F-FDG PET images for use in clinical practice.},
}

@article {pmid41529922,
year = {2026},
author = {Zhao, J and Qu, Z and Li, Z and Zhou, L and Hu, Y and Yu, S and Chen, X and Shu, H and , },
title = {Neurotransmitter-based machine-learning model for distinguishing Alzheimer's disease and mild cognitive impairment.},
journal = {The Journal of international medical research},
volume = {54},
number = {1},
pages = {3000605251409886},
doi = {10.1177/03000605251409886},
pmid = {41529922},
issn = {1473-2300},
mesh = {Humans ; *Alzheimer Disease/diagnosis/metabolism/diagnostic imaging/pathology ; *Cognitive Dysfunction/diagnosis/metabolism/diagnostic imaging/pathology ; *Machine Learning ; Male ; Female ; Aged ; Magnetic Resonance Imaging ; *Neurotransmitter Agents/metabolism ; Gray Matter/pathology/diagnostic imaging/metabolism ; Atrophy ; Diagnosis, Differential ; Aged, 80 and over ; ROC Curve ; Neuroimaging/methods ; Case-Control Studies ; Brain/pathology/diagnostic imaging/metabolism ; },
abstract = {ObjectiveAlzheimer's disease and mild cognitive impairment involve brain atrophy, but neurotransmitter changes and their clinical implications are not well defined. This study aimed to examine the relationship between gray matter atrophy and neurotransmitter distributions and to build machine-learning models using gray matter-neurotransmitter co-localization as features.MethodsAmong 262 participants from the Alzheimer's Disease Neuroimaging Initiative (140 with Alzheimer's disease, 50 with mild cognitive impairment, and 72 controls), we used structural magnetic resonance imaging and voxel-based morphometry (family-wise error < 0.05), and JuSpace toolbox was used to assess the spatial correlation between gray matter atrophy and 13 neurotransmitter maps. We applied a train/validation/fixed test split (the test set was never used for selection or training); features were screened by univariate regression and least absolute shrinkage and selection operator regression, and models trained with nested 10-fold cross-validation were evaluated by the area under the receiver operating characteristic curve.ResultsBoth Alzheimer's disease and mild cognitive impairment showed gray matter loss in temporal, frontal, and cingulate areas. Atrophy was correlated with serotonergic, dopaminergic, and glutamatergic systems (false-discovery rate < 0.05). In mild cognitive impairment, reduced metabotropic glutamate receptor 5/μ-opioid receptor-gray matter correlation was associated with higher depression scores (r = -0.44, p = 0.001; r = -0.44, p = 0.001). The Random Forest model achieved an area under the receiver operating characteristic curve of 0.821, and Shapley additive explanations analysis confirmed key feature contributions.ConclusionNeurotransmitter-linked gray matter changes contribute to the pathology of Alzheimer's disease and mild cognitive impairment. The machine-learning model accurately differentiates these conditions, suggesting its utility for early diagnosis and disease staging.},
}

Humans
*Alzheimer Disease/diagnosis/metabolism/diagnostic imaging/pathology
*Cognitive Dysfunction/diagnosis/metabolism/diagnostic imaging/pathology
*Machine Learning
Male
Female
Aged
Magnetic Resonance Imaging
*Neurotransmitter Agents/metabolism
Gray Matter/pathology/diagnostic imaging/metabolism
Atrophy
Diagnosis, Differential
Aged, 80 and over
ROC Curve
Neuroimaging/methods
Case-Control Studies
Brain/pathology/diagnostic imaging/metabolism

@article {pmid41529736,
year = {2026},
author = {Jiang, F and Yi, Y and Zhang, J and Tan, A and Qin, X and Zhong, X and Wang, P and Xiao, J and Zhou, B and Li, J},
title = {Cortical β-amyloid deposition and cognitive impairment in remitted late-onset depression: An [18F]Florbetapir PET study.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121067},
doi = {10.1016/j.jad.2025.121067},
pmid = {41529736},
issn = {1573-2517},
abstract = {BACKGROUND: Late-onset depression (LOD) has been associated with increased risk of Alzheimer's disease (AD), but amyloid-β (Aβ) abnormalities may not be uniformly present across all clinical subtypes. This study examined cortical Aβ deposition in remitted LOD (RLOD) patients with and without cognitive impairment to clarify heterogeneity in AD-related pathology.

METHODS: Eighty participants were enrolled, including 30 cognitively impaired RLOD (RLOD-CI), 30 cognitively unimpaired RLOD (RLOD-CU), and 20 healthy controls (HC). All underwent [^18F]Florbetapir PET imaging, with global Aβ positivity defined as SUVR ≥1.10. Regional SUVR values were quantified using the AAL3 atlas. Episodic memory performance was normalized using Z-scores derived from the HC group. Group differences and correlation analyses were performed with appropriate statistical corrections.

RESULTS: RLOD-CI patients showed significantly elevated Aβ burden in multiple cortical regions-including the frontal, temporal, parietal, occipital, cingulate, precuneus and global cortices-compared with HC and RLOD-CU (all p < 0.05). Aβ positivity rates were 66.7 % (RLOD-CI), 36.7 % (RLOD-CU), and 35.0 % (HC). Within the RLOD-CI group, frontal SUVRs were negatively correlated with immediate (r = -0.48, p = 0.0067) and delayed (r = -0.42, p = 0.022) memory Z-scores, while no other cognitive domains showed significant associations.

CONCLUSIONS: Aβ deposition is selectively increased in cognitively impaired-but not cognitively unimpaired-RLOD patients, supporting RLOD-CI as a distinct phenotype potentially reflecting prodromal AD. The modest association between frontal Aβ burden and episodic memory further underscores heterogeneity within LOD. Longitudinal studies are warranted to clarify progression risk and evaluate the predictive value of Aβ imaging in this population.},
}

@article {pmid41529520,
year = {2026},
author = {Chen, J and Wang, L and Zhou, Y and Zhao, S and Chen, Q and Zheng, K},
title = {The liver as a metabolic and immune hub in Alzheimer's disease: From mechanisms to therapeutic opportunities.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {3},
pages = {100478},
doi = {10.1016/j.tjpad.2026.100478},
pmid = {41529520},
issn = {2426-0266},
abstract = {Research on Alzheimer's disease (AD) has traditionally focused on the brain. However, emerging evidence indicates that the liver acts as a silent partner in neurodegeneration. As a core hub for metabolic and immune regulation, the liver communicates bidirectionally with the brain via the liver-brain axis, participating in the regulation of various neurophysiological processes, including neurotransmitter regulation, feeding behavior, and cognition. This review summarizes how liver-derived hepatokines, inflammatory mediators, and metabolic products modulate brain function. We highlight that liver dysfunction disrupts the expression of critical molecules-including fibroblast growth factor 21, insulin-like growth factor 1, lipopolysaccharide, and lipocalin-2-thereby driving AD progression by impairing pathological protein clearance, activating neuroinflammation, exacerbating insulin resistance and oxidative stress, and disrupting lipid metabolism. We also discuss the therapeutic potential of targeting the liver-brain axis through lifestyle interventions (e.g., exercise and diet) and pharmacological approaches, to identify novel strategies to delay AD progression. In summary, we underscore the pivotal role of the liver-brain axis in AD pathogenesis and propose it as a promising target for early diagnosis and innovative therapies.},
}

@article {pmid41530402,
year = {2026},
author = {Shen, C and Wu, F and Liao, B and Wang, J and Li, Q and , },
title = {Generative Adversarial Networks Based on Fine-Grained Image Recognition for the Progression Prediction of Progressive Mild Cognitive Impairment.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {},
number = {},
pages = {},
pmid = {41530402},
issn = {1867-1462},
support = {62362027//National Nature Science Foundation of China/ ; 62362028//National Nature Science Foundation of China/ ; 2020YFB2104400//National Key R and D Program of China/ ; 824MS063//Natural Science Foundation of Hainan Province/ ; 824MS062//Natural Science Foundation of Hainan Province/ ; 122MS055//Natural Science Foundation of Hainan Province/ ; },
abstract = {Progressive mild cognitive impairment (pMCI) often develops into Alzheimer's disease (AD), whereas stable mild cognitive impairment (sMCI) remains cognitively unchanged. Therefore, early identification of pMCI based on multimodal neuroimaging data (e.g., MRI, PET) is clinically valuable. However, limited multimodal data reduces complementary information across modalities and degrades prediction performance. Existing generative adversarial networks (GANs) often overlook local information when synthesizing cross-modal neuroimages, leading to suboptimal image quality. Motivated by these shortcomings, we propose a generative adversarial network (FGGAN) based on fine-grained image recognition for cross-modal image synthesis and pMCI progression prediction. FGGAN comprises a GAN, a feature depth extraction (FDE) module, and a classifier module. The GAN synthesizes high-quality missing modality data by leveraging local and global cues from the input image, while extracting multimodal feature representations. The FDE refines semantic features to improve feature adaptation for the classifier, which predicts pMCI progression from fused multimodal features. Results from the ADNI dataset indicate that FGGAN achieves superior performance in image synthesis quality and disease classification.},
}

@article {pmid41530250,
year = {2026},
author = {Hu, M and Qin, T and Gonzalez, R and Freedman, VA and Zahodne, LB and Melipillán, ER and Murphey, YL},
title = {A novel vision transformer model produces clock drawing test scores as accurate as expert human coders.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-34064-6},
pmid = {41530250},
issn = {2045-2322},
abstract = {Alzheimer's disease and related dementias is a growing public health concern. The clock-drawing test, where subjects draw a clock, typically with hands showing 11:10, has been widely used for dementia screening. A limitation of including the clock-drawing test in large-scale studies is that it requires manual coding, which could result in biases if coders interpret and implement coding rules differently. This study created and evaluated an intelligent Clock Scoring system built with deep learning neural networks to automatically code clock-drawing images. We used a large, publicly available repository of clock-drawing images from the 2011-2019 National Health and Aging Trends Study (NHATS) and compared three advanced DLNN methods - ResNet101, EfficientNet and Vision Transformers - in coding clock-drawing images into binary and ordinal (0 to 5) scores. Unlike the traditional nominal classification approach, which treats all categories as unordered (e.g., cats and dogs), we introduced structured ordering into the coding system, which recognizes that higher scores reflect better representation of the clock than lower scores. We also compared deep learning-coded clock images with manual coding, using expert coding as the benchmark to evaluate accuracy. Results suggest that Vision Transformers achieves clock scoring accuracy comparable to expert human coders (weighted kappa = 0.81), outperforming both ResNet101 and EfficientNet (weighted kappa = 0.56-0.73). The ordinal coding system has the ability to allow researchers to minimize either under- or over-estimation errors. Our Vision Transformer-based coding system has been used in NHATS' annual clock-coding since 2022.},
}

@article {pmid41530054,
year = {2026},
author = {Sloand, TJ and Dunham, BP and Niedringhaus, M and West, EA},
title = {Aberrant medial prefrontal cortex activity and flexible behavior in the TgF344-AD rat model of Alzheimer's disease.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1387-25.2026},
pmid = {41530054},
issn = {1529-2401},
abstract = {Executive dysfunction can precede the accumulation of canonical neuropathological markers and severe dementia in Alzheimer's disease (AD) patients often characterized by memory changes. Deficits in executive function including flexible behavior, i.e., the ability to shift behavior following negative consequences, are often mediated by the prefrontal cortex. However, it is unknown how medial prefrontal cortex activity is altered in behaving Tg-F344-AD rats, which exhibit age-dependent AD pathology and memory deficits. We tested the ability of in 6-7-month-old TgF344-AD rats to learn reward predictive cues and to shift behavior away from cues following outcome devaluation while recording mPFC neurons (wild-type, 10 males and 7 females; TgF344-AD, 8 males and 9 females). Rats were presented with two distinct cues as conditioned stimuli (CS+) predicting two distinct outcomes over learning. Then, a conditioned taste aversion to one outcome was induced and rats were evaluated for their ability to avoid the CS+ associated with the devalued outcome. We found a loss of motivated behavior during learning and impaired flexible behavior in 6-7-month-old AD rats relative to controls. In addition, there was differential aberrant mPFC encoding of cue-outcome associations in AD rats during conditioning and following devaluation. AD rats showed fewer neurons during conditioning that encode both the cue and the outcome. Also, AD rats showed a greater proportion of neurons that exhibited an excited response to reward predictive cues following devaluation. Together, these data contribute to our understanding of alterations in mPFC that may underlie prodromal AD behavioral deficits to inform future treatments.Significance Statement Before memory loss becomes severe in Alzheimer's disease, many people show early problems with decision-making and behavioral flexibility, associated with prefrontal cortex control. Here, we show that rats developed to model Alzheimer's disease have abnormal mPFC activity during tasks that require learning and adapting to changing outcomes. These animals were less able to adjust their behavior when reward value changed, and their mPFC neurons failed to properly link cues with expected outcomes. These findings suggest that early dysfunction in the mPFC may underlie some of the behavioral phenotypes associated with Alzheimer's disease, highlighting this brain region as a potential early target for therapeutic intervention.},
}

@article {pmid41529823,
year = {2026},
author = {Kinsell, HS and Thomas, K and Ilich, JZ and Reilly, A and Harman, JS and Thomasson, M},
title = {Hearing Loss and Aggressive Behavior: Results From a Large, Retrospective Study of Older Adults Receiving Home Care Services in 2 US States.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {106076},
doi = {10.1016/j.jamda.2025.106076},
pmid = {41529823},
issn = {1538-9375},
abstract = {OBJECTIVES: To examine the relationship between hearing difficulty and aggressive behavior among adults aged ≥65 years receiving Medicaid home care services in 2 US states.

DESIGN: A cross-sectional analysis was conducted using secondary data collected from the interRAI Home Care and Community Health Assessment.

SETTING AND PARTICIPANTS: Participants included 134,382 adults aged ≥65 years who received home care services in New York and Michigan in 2017 and had an initial interRAI assessment and independent living status.

METHODS: The association of hearing loss with the odds of exhibiting aggressive behavior was estimated using ordered logistic regression controlling for age, sex, and presence of Alzheimer's disease or dementia. Hearing difficulty had 4 levels, and aggressive behaviors was a 3-level variable.

RESULTS: Individuals with hearing difficulties had higher odds of showing signs of aggressive behaviors than those with no difficulty in hearing. The odds of aggressive behaviors increased as hearing worsened. After adjustment, compared with individuals without hearing loss, older adults with severe or total hearing loss had twice the odds of displaying signs of aggressive behavior (odds ratio, 2.02; 95% CI, 1.81-2.26). Additionally, individuals with moderate hearing loss had almost 1.5 times the odds of showing aggressive behaviors (OR, 1.44; 95% CI, 1.34-1.55) CONCLUSIONS AND IMPLICATIONS: This research suggests that hearing loss is an important factor to assess and address among older adults. Results of this study illustrate that age-related sensory declines can impact other health-related behavioral conditions. In home care settings, sensory and behavioral changes should be monitored and assessed at regular intervals as part of multidisciplinary care planning. Performing routine hearing tests may result in earlier intervention and better management of care for home care populations, reducing caregiver burden particularly in individuals with multiple comorbidities. Early interventions may include incorporating routine hearing screenings, behavioral monitoring linked to sensory decline, and greater use of assistive devices or other enhanced communication strategies.},
}

@article {pmid41529684,
year = {2026},
author = {Lee, E and Kim, S and Zhu, CL and Acquarone, E and Kim, S and Lo, A and Omar, OMF and Taddese, M and Gradinaru, V and Murphy, PA and Agalliu, D and Arancio, O and An, JY and Kim, M},
title = {Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.},
journal = {Cell reports},
volume = {},
number = {},
pages = {116621},
doi = {10.1016/j.celrep.2025.116621},
pmid = {41529684},
issn = {2211-1247},
abstract = {Disruption of the blood-brain barrier (BBB) increases vascular permeability and promotes neuroinflammation, contributing to Alzheimer's disease (AD) progression. However, the molecular drivers of BBB dysfunction and neuroinflammation in AD remain poorly defined. Here, we identify angiopoietin-2 (ANGPT2) as a central mediator of BBB breakdown and AD progression. Transcriptomic analyses of human AD brains revealed elevated ANGPT2 expression in endothelial cells correlating with disease severity. In 5xFAD mice, endothelial-specific Angpt2 deletion reduced β-amyloid deposition, while Angpt2 overexpression via an adeno-associated viral vector exacerbated the plaque burden. Mechanistically, ANGPT2 suppression of TIE2 signaling increased vascular leakage and fibrin deposition, triggering microglial activation and neuroinflammatory responses that accelerated disease progression. Single-nucleus transcriptomic analyses further revealed Angpt2-driven microglial dysfunction and neuronal impairment consistent with memory deficits observed in behavioral assays. These findings establish ANGPT2 as a critical driver of BBB dysfunction and neuroinflammation in AD and highlight its therapeutic potential.},
}

@article {pmid41528923,
year = {2026},
author = {Barczak, A and Krempa-Kowalewska, A},
title = {Validation of the Polish version of Addenbrooke's Cognitive Examination III in Mild Cognitive Impairment and Alzheimer's Disease Dementia.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1-16},
doi = {10.1159/000549856},
pmid = {41528923},
issn = {1421-9824},
abstract = {INTRODUCTION: The Addenbrooke's Cognitive Examination III (ACE-III) is a widely recognized cognitive screening tool; however, its diagnostic accuracy and optimal cut-off values for distinguishing mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD-D) have not been established in the Polish population. This study aimed to evaluate the reliability, diagnostic performance, and optimal cut-off scores of the ACE-III in differentiating between controls, MCI, and AD-D patients.

METHODS: A total of 1,265 Polish participants were assessed: 767 with AD-D (321 men; mean age, 74.9 ± 8.2 years), 216 with MCI (90 men; mean age, 72.2 ± 8.4 years), and 282 controls (77 men; mean age, 67.1 ± 8.7 years). All underwent cognitive screening using the ACE-III and the Mini-Mental State Examination (MMSE). Group differences were examined using the Kruskal-Wallis test, while receiver operating characteristic (ROC) analyses determined diagnostic accuracy and optimal cut-off points. ANCOVA with bootstrap resampling was used to control for age and education.

RESULTS: Internal consistency of the ACE-III was strong (McDonald's ω = 0.889). The ACE-III demonstrated superior diagnostic accuracy compared with the MMSE, with optimal cut-offs of 88.5 (sensitivity, 98%; specificity, 92%) for distinguishing controls from MCI and 72.5 (sensitivity, 90%; specificity, 76%) for distinguishing MCI from AD-D.

CONCLUSIONS: The ACE-III is a reliable and sensitive tool for detecting early cognitive decline in the Polish population. Its superior diagnostic utility compared with the MMSE, particularly in identifying early neurocognitive impairment, supports its use in timely diagnosis and intervention.},
}

@article {pmid41528918,
year = {2026},
author = {Cui, J and Ye, W and Li, S and Wen, J and Zhu, Q},
title = {Adjacent-aware Modality Recovery based on Incomplete Multi-Modal Brain Disease Diagnosis.},
journal = {IEEE transactions on medical imaging},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TMI.2026.3654000},
pmid = {41528918},
issn = {1558-254X},
abstract = {Multi-modal learning is extensively applied to diagnose brain diseases such as epilepsy and Alzheimer's disease. However, incomplete multi-modal data, where some modalities are unavailable or difficult to collect, limits the effectiveness of conventional methods. Additionally, existing approaches often overlook semantic relationships between neighbors with the same-label and latent information in missing modalities. To address these challenges, we propose an adjacent-aware distillation recovery framework designed for incomplete multi-modal learning, with a focus on diagnosing representative brain diseases, i.e. epilepsy and Alzheimer's disease. The key novelty of our framework lies in its joint design of adjacent-aware modality recovery and multi-modal representation learning in a single end-to-end pipeline. Specifically, we introduce a label-guided adjacent-aware recovery module that uses a self-attention mechanism to exploit neighbor semantics and generate distribution-consistent features for high-quality modality reconstruction. The recovered features are then refined through a knowledge distillation pathway into a modality generator, enhancing generalization under severe data incompleteness. For multi-modal representation learning, the recovered modality information is fused with the original incomplete information to enhance feature extraction and representation. Extensive experiments demonstrate the effectiveness of our method in diagnosing epilepsy and Alzheimer's disease.},
}

@article {pmid41528688,
year = {2026},
author = {Rattanatanyapat, P and Suan-Ek, P and Saokaew, S and Phisalprapa, P and Mongkhon, P},
title = {Antidementia drugs and nursing home placement: a systematic review and meta-analysis.},
journal = {European geriatric medicine},
volume = {},
number = {},
pages = {},
pmid = {41528688},
issn = {1878-7649},
support = {Fundamental Fund 2025 (5044/2567)//University of Phayao and Thailand Science Research and Innovation Fund/ ; },
abstract = {PURPOSE: The association between antidementia drugs (ADDs) use and the risk of nursing home placement (NHP) remains inconclusive. This study aimed to investigate the effects of ADDs, including cholinesterase inhibitors (CEIs) and memantine, on NHP among individuals with dementia.

METHODS: A systematic search of PubMed, Embase, Cochrane Library and ClinicalTrials.gov was conducted up to 16 March 2024 and updated on 25 August 2025. Randomized controlled trials (RCTs) or observational studies investigating the use of ADDs and NHP were included. Hazard ratios (HRs) with 95% confidence intervals (CI) were pooled using the DerSimonian-Laird random-effects model.

RESULTS: Of 1,373 records, three RCTs and nine observational studies were included, encompassing different comparators. Meta-analyses were conducted separately by study design. In RCT, the single trial comparing any ADDs versus non-use (N = 1; donepezil vs placebo) showed no significant difference in NHP. In head-to-head RCT comparisons, one trial suggested a non-significant trend toward higher NHP risk with memantine versus donepezil. Among observational studies, a meta-analysis of five observational studies suggested a lower NHP risk with any ADDs in Alzheimer's disease (pooled HR = 0.43, 95% CI: 0.32-0.58, I[2] = 40.39%, p < 0.001) and mixed dementia (pooled HR = 0.84, 95% CI: 0.72-0.97, I[2] = 0.00%, p = 0.019). Pooled observational head-to-head comparisons likewise showed no significant differences between donepezil and rivastigmine (n = 3), donepezil and galantamine (n = 2), or CEIs + memantine versus CEIs monotherapy (n = 2). These observational estimates may be affected by residual confounding and other biases and should be interpreted with caution. By GRADE, certainty was low for the RCTs evidence and very low for the pooled observational studies of ADDs or CEIs versus non-use, and for head-to-head and combination therapy comparisons.

CONCLUSIONS: RCTs, rated as low-certainty evidence, suggest that ADDs may have no effect on NHP, whereas observational studies, rated as very low-certainty evidence, suggest that ADDs may be associated with a reduced risk of NHP among individuals with dementia. Given the overall uncertainty, high-quality, adequately powered prospective trials with longer follow-up are required to clarify these associations and to assess whether a causal relationship exists.},
}

@article {pmid41528676,
year = {2026},
author = {Soke, F and Ataoglu, NEE and Gulsen, C and Yorulmaz, DK and Gulfirat, FN and Bora, HAT},
title = {Timed 360° turn test in people with Alzheimer's disease: a reliability and validity study.},
journal = {Irish journal of medical science},
volume = {},
number = {},
pages = {},
pmid = {41528676},
issn = {1863-4362},
abstract = {BACKGROUND: Turning is an essential and challenging activity in daily life but is not specifically assessed for people with Alzheimer's disease (PwAD). The timed 360º turn test (360TT) is a specific tool assessing turning ability; however, its reliability and validity have not been established in Alzheimer's disease (AD).

AIMS: To investigate: (1) the test-retest reliability of the 360TT in PwAD; (2) the standard error of measurement (SEM) and minimum detectable change (MDC) in the 360TT times; (3) the concurrent and known-groups validity of the 360TT times.

METHODS: This cross-sectional study included 33 PwAD and 32 healthy people. The 360TT was administered along with the Berg Balance Scale, Timed Up and Go Test, and Mini-Mental State Examination. The test-retest reliability of the 360TT was examined by performing it twice at a 7-10 day interval for PwAD.

RESULTS: Test-retest reliability of the 360TT was excellent for the dominant and non-dominant sides (ICC = 0.957 and ICC = 0.916, respectively). The SEM95 and MDC95 values were 0.33 s and 0.91 s for the dominant side, while these values were 0.31 s and 0.85 s for the non-dominant side. The 360TT was correlated with the BBS, TUG, and MMSE in both sides (p < 0.05). PwAD took longer to complete the 360TT on both sides compared to healthy people (p < 0.001).

CONCLUSIONS: The 360TT is a reliable and valid method in the evaluation of turning ability for PwAD. Clinicians and researchers can also use the 360TT to quantify changes in turning ability in AD.},
}

@article {pmid41528665,
year = {2026},
author = {Kumar, A and Rakshit, D and Saharia, N and Tiwari, P and Mugale, MN and Mishra, A},
title = {Dietary Isoflavone Biochanin A Attenuates Aluminium Chloride-Induced Sporadic Alzheimer's Disease and Associated Neurobehavioral Alterations Through NRF2-HO1 Pathway Activation and NLRP3 Inflammasome Suppression.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {359},
pmid = {41528665},
issn = {1559-1182},
mesh = {Animals ; *Genistein/pharmacology/therapeutic use/administration & dosage ; Aluminum Chloride ; *Alzheimer Disease/chemically induced/metabolism/drug therapy/pathology ; *NF-E2-Related Factor 2/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Inflammasomes/metabolism/drug effects ; Male ; Signal Transduction/drug effects ; Mice ; Oxidative Stress/drug effects ; *Behavior, Animal/drug effects ; *Heme Oxygenase-1/metabolism ; Amyloid beta-Peptides/metabolism ; Neuroprotective Agents/pharmacology ; Mice, Inbred C57BL ; },
abstract = {Alzheimer's disease (AD), a debilitating neurodegenerative disorder, currently lacks effective curative treatments. Growing evidence implicates aluminium, a widely prevalent environmental metal, in the pathogenesis of AD due to its ability to induce oxidative stress, neuroinflammation, cholinergic dysfunction, and amyloid-beta (Aβ) deposition, ultimately leading to cognitive decline. Biochanin A (BCA), a naturally occurring isoflavone, exhibits well-documented antioxidant, anti-inflammatory, and neuroprotective activities, including acetylcholinesterase (AChE) inhibition. However, its specific therapeutic potential in AD models has remained largely unexplored. This study evaluates the protective effects of BCA against aluminium chloride (AlCl3)-induced AD-like pathology in mice. Animals received daily oral administration of AlCl3 (100 mg/kg) for 6 weeks, with or without concurrent BCA treatment (5, 10, and 20 mg/kg). During the final week, comprehensive neurobehavioral assessments were conducted. Thereafter, hippocampal tissues were analyzed for biochemical, molecular, and elemental analyses, and intact brains were examined histologically. AlCl3 exposure significantly impaired neurobehavioral performance, elevated oxidative stress, disrupted cholinergic function, intensified neuroinflammation, promoted amyloid aggregation, and induced neurodegeneration. Notably, BCA supplementation dose-dependently ameliorated these pathological alterations. BCA treatment improved neurobehavioral deficits (P < 0.05), reduced oxidative markers (P < 0.01), restored cholinergic function by lowering AChE activity (P < 0.01), attenuated inflammatory mediators (P < 0.01), reduced amyloid and aluminium deposition (P < 0.001), and alleviated AlCl3-induced neurodegeneration. Overall, our findings indicate that BCA confers neuroprotection primarily through activation of the NRF2-HO-1 signaling pathway and through suppression of the NLRP3 inflammasome, highlighting its promise as a potential therapeutic candidate for AD.},
}

Animals
*Genistein/pharmacology/therapeutic use/administration & dosage
Aluminum Chloride
*Alzheimer Disease/chemically induced/metabolism/drug therapy/pathology
*NF-E2-Related Factor 2/metabolism
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Inflammasomes/metabolism/drug effects
Male
Signal Transduction/drug effects
Mice
Oxidative Stress/drug effects
*Behavior, Animal/drug effects
*Heme Oxygenase-1/metabolism
Amyloid beta-Peptides/metabolism
Neuroprotective Agents/pharmacology
Mice, Inbred C57BL

@article {pmid41528540,
year = {2026},
author = {Nishanth, DS and Sinha, U and Verma, T and Kalidass, B and Thirumuruganandham, SP and Kodiveri Muthukaliannan, G},
title = {Molecular Mechanisms and Therapeutic Potential of Degron-Mediated Proteostasis Regulation in Neurodegenerative Diseases.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-025-01659-6},
pmid = {41528540},
issn = {1573-6830},
abstract = {Aberrant aggregation of specific proteins-such as amyloid beta, α-synuclein, tau, TDP-43, and PrPSc-is a hallmark anomaly in the brain micro-environment, leading to a cascade of pathological events including neuroinflammation, neuronal death, cognitive impairment, and memory loss. The dysregulation in cellular protein homeostasis promotes pathological protein aggregation and hastening disease progression. Degrons are short amino acid motifs within proteins that are recognized by E3 ubiquitin ligases, which target them for degradation via the ubiquitin-proteasome system or autophagy. Recent studies emphasize that alterations in degron sequences, changes after translation or structural modifications can hinder protein homeostasis, leading to their accumulation and contributing neural toxicity. This review integrates the mechanistic role of degron with their pathological relevance and therapeutic significance in neurodegenerative diseases includes Alzheimer's disease, Parkinson's disease, Sclerosis, frontotemporal dementia, and prion diseases and further investigates the translational potential of degron-targeting techniques, including emerging biotechnological startups developing degron-based therapeutic platforms.},
}

@article {pmid41528304,
year = {2025},
author = {Piaszczynska, W and Budak, M and Rowe, B and Moallemian, S and Fausto, BA and Ringman, JM and Gluck, MA},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e106881},
doi = {10.1002/alz70856_106881},
pmid = {41528304},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Biomarkers ; Magnetic Resonance Imaging ; Middle Aged ; Mutation/genetics ; Neuropsychological Tests ; Disease Progression ; *Temporal Lobe/pathology/diagnostic imaging ; Aged ; Adult ; Neuroimaging ; Cohort Studies ; },
abstract = {BACKGROUND: Autosomal Dominant Alzheimer's disease (ADAD) due to mutations in PSEN1, APP, and PSEN2 offers a unique framework for elucidating the neuropathological mechanisms underlying early disease stages. Given the critical role of the MTL in memory and cognitive processing, the ADAD mutations have yet to be thoroughly investigated regarding its impact on medial temporal lobe (MTL) dynamics and subfield-specific integrity in FAD. This study focuses on identifying biomarkers for early disease progression by examining ADAD mutations on MTL network flexibility, subfield volumetric integrity, and associated cognitive outcomes among autosomal dominant AD.

METHOD: The cohort comprised 36 participants (28 women) carrying ADAD mutations (Meanage=39.11, SDage=12.16) who underwent genotyping, cognitive assessment using the Cognitive Abilities Screening Instrument (CASI), and brain neuroimaging with a Siemens Magnetom 3T Trio scanner. ANCOVA and Linear Regression analysis were applied using age as a covariate.

RESULT: ADAD mutation carriers exhibited significantly reduced MTL network flexibility (F(1)= 4.551, 𝜂p [2]= .121, p = .040), indicating altered dynamic connectivity, despite no observed volumetric differences in structural analyses (p > .05). Notably, volumetric measures of the right entorhinal cortex were positively correlated with CASI scores (b = .492, t = 2.837, p = .009).

CONCLUSION: Among ADAD mutation carriers, reduced MTL dynamic network flexibility suggesting early functional changes despite no significant differences in subfield volumes. Additionally, larger right entorhinal cortex volume was associated with better cognitive performance, highlighting its role in preserving cognitive function. These findings suggest that dynamic functional network alterations within the MTL region may serve as early indicators of disease progression in ADAD, even before structural atrophy becomes apparent. This study also underscores the need for integrating network-based and subfield-specific analyses while considering ADAD mutation status to better understand disease mechanisms.},
}

Humans
Female
Male
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Biomarkers
Magnetic Resonance Imaging
Middle Aged
Mutation/genetics
Neuropsychological Tests
Disease Progression
*Temporal Lobe/pathology/diagnostic imaging
Aged
Adult
Neuroimaging
Cohort Studies

@article {pmid41528085,
year = {2026},
author = {Labos, E and Cristalli, D and Deschle, F and Colli, L and Berrios, W and Dorman, G and Fernández, MC and Frontera, S and Katz, M and Mangone, C and Márquez, F and Porta, O and Rubiño, V and Russo, MJ and Ollari, J},
title = {[Not Available].},
journal = {Vertex (Buenos Aires, Argentina)},
volume = {36},
number = {170, oct.-dic.},
pages = {41-63},
doi = {10.53680/vertex.v36i170.943},
pmid = {41528085},
issn = {0327-6139},
mesh = {Humans ; *Dementia/diagnosis/complications/psychology ; *Cognition ; },
abstract = {La enfermedad demencial se caracteriza por un deterioro progresivo de las habilidades cognitivas y funcionales. Si bien la demencia de mayor prevalencia es la Enfermedad de Alzheimer el amplio espectro de otras formas de presentación como la demencia vascular, la demencia frontotemporal o la demencia por cuerpos de Lewy, entre otras, implica un gran desafío diagnóstico. Esta instancia resulta altamente complicada ya que generalmente la enfermedad demencial se presenta en sus inicios con una variada superposición de manifestaciones clínicas y cognitivas, así como con una gran heterogeneidad en los hallazgos en las exploraciones de imágenes por resonancia magnética que hace difícil su precisión. Se describen los perfiles cognitivos de la enfermedad de Alzheimer, la demencia vascular, la demencia frontotemporal en su variable conductual, la demencia con cuerpos de Lewy, las demencias focales como las afasias progresivas primarias, la demencia por enfermedad de Parkinson y el LATE, demencia tardía con gran similitud a la EA. Considerando que no siempre es posible acceder a estudios de complejidad como los biomarcadores o neuroimágenes, el objetivo del presente trabajo es brindar un panorama actual de los perfiles cognitivos de inicio y progresión que resulte de utilidad clínica y que oriente a un posible diagnóstico diferencial.},
}

Humans
*Dementia/diagnosis/complications/psychology
*Cognition

@article {pmid41528082,
year = {2026},
author = {Bagnati, PM and Allegri, RF and Demey, I and Bártoli, G and Bérgamo, Y and Campos, J and Castro, D and Chrem Méndez, P and Cristalli, D and Fernandez, C and Fernández, ML and García Lombardi, JP and Kremer, JL and Magrath Guimet, N and Ollari, J and Osa Sanz, E and Rojas, G and Russo, MJ and Sarasola, D and Surace, E and Vazquez, S and Waisman Campos, M and Zuin, D},
title = {[Not Available].},
journal = {Vertex (Buenos Aires, Argentina)},
volume = {36},
number = {170, oct.-dic.},
pages = {85-102},
doi = {10.53680/vertex.v36i170.946},
pmid = {41528082},
issn = {0327-6139},
mesh = {Humans ; *Dementia/diagnosis ; Argentina ; Algorithms ; },
abstract = {El Consenso Argentino para el diagnóstico de las demencias es una iniciativa de la Asociación Argentina de Psiquiatría Biológica (AAPB). Este documento tuvo como objetivo principal elaborar un instrumento eficiente para el diagnóstico temprano de la demencia, dirigido al médico de atención primaria, y al especialista (neurólogo, psiquiatra, geriatra, clínico u otros). Durante un periodo de 5 meses de trabajo -desde agosto a diciembre del 2024- (y una breve revisión posterior a la Conferencia Internacional de Alzheimer -AAIC Toronto 2025, Julio 2025- para sumar actualización), un comité de expertos integrado por 23 profesionales se abocaron a analizar y discutir la mejor información y evidencia actualizada para lograr la sistemática diagnóstica de la demencia, focalizada en la más común de ellas en Occidente, la enfermedad de Alzheimer (EA). El documento se divide en 3 partes: esta primera donde se describe el panorama actual de la demencia en el mundo, su diferencia con el envejecimiento usual o típico, los criterios diagnósticos recientes, y los algoritmos diagnósticos para el médico de atención primaria y para el especialista. Una segunda parte, donde se aborda la sistemática de evaluación diagnóstica: neurocognitiva, neuropsiquiátrica, los biomarcadores (laboratorio, LCR, biomarcadores en plasma, neuroimágenes, genética) y la evaluación funcional. Por último, una tercera parte que incluye la descripción de los diferentes tipos de demencia con sus características clínicas y criterios diagnósticos actuales, poniendo énfasis en el diagnóstico diferencial.},
}

Humans
*Dementia/diagnosis
Argentina
Algorithms

@article {pmid41527932,
year = {2026},
author = {Connell, E and Le Gall, G and McArthur, S and Lang, L and Breeze, B and Liaquat, M and Pontifex, MG and Sami, S and Pourtau, L and Gaudout, D and Müller, M and Vauzour, D},
title = {A novel Mediterranean diet-inspired supplement reduces hippocampal amyloid deposits and microglial activation through the modulation of the microbiota gut-brain axis in 5xFAD mice.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2614030},
doi = {10.1080/19490976.2026.2614030},
pmid = {41527932},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Microglia/drug effects/metabolism ; *Hippocampus/metabolism/drug effects/pathology ; Mice ; Male ; *Diet, Mediterranean ; Mice, Transgenic ; *Alzheimer Disease/metabolism/diet therapy/microbiology ; Female ; *Dietary Supplements ; Disease Models, Animal ; Amyloid beta-Peptides/metabolism ; Humans ; Brain-Gut Axis ; Brain/metabolism ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is projected to increase in prevalence, heightening the need for strategies to alleviate its neuropathological burden. The bioactive constituents of a Mediterranean-style diet are well-recognised for their neuroprotective properties. Due to their capacity to alter the gut microbiome composition, these benefits may involve modulation of the microbiota-gut-brain axis. In this study, we investigated whether a novel supplement enriched with key Mediterranean diet-derived bioactives (Neurosyn240) could reduce amyloid deposition and microglial activation in 5xFAD mice, a transgenic model of AD, through microbiota-mediated mechanisms.

METHODS: Male and female 5xFAD transgenic mice (n = 16 per sex) were randomly assigned to receive either a standard control diet or a diet supplemented with Neurosyn240 for 12 weeks. Employing a multi-omics approach, gut microbiota composition was profiled using 16S rRNA ampliconsequencing, serum metabolites were quantified via targeted metabolomics, and hippocampal gene expression was analysed through qPCR and RNA sequencing. Neuropathological markers, including amyloid-β deposition and microglial activation, were evaluated using immunofluorescence staining. Statistical analyses were performed using two-way ANOVA to examine the main effects of diet and sex and their interaction.

RESULTS: Neurosyn240 significantly shifted the gut microbiome composition, which was associated with increased circulatory serotonin levels and decreased kynurenine and bile acids (TCA, HDCA, TDCA, CDCA and LCA) concentrations. In the brain, Neurosyn240 consumption led to a significant reduction in hippocampal amyloid deposits and Iba-1 positive microglia (p<0.05), which were associated with decreased LCA and increased serotonin, respectively. Hippocampal RNA sequencing further highlighted the upregulation of genes involved in promoting amyloid beta clearance mechanisms.

CONCLUSIONS: Together, these findings highlight novel neuroprotective effects of Neurosyn240 in modulating metabolite-mediated pathways of the microbiota-gut-brain axis, accentuating its therapeutic potential against AD progression.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Microglia/drug effects/metabolism
*Hippocampus/metabolism/drug effects/pathology
Mice
Male
*Diet, Mediterranean
Mice, Transgenic
*Alzheimer Disease/metabolism/diet therapy/microbiology
Female
*Dietary Supplements
Disease Models, Animal
Amyloid beta-Peptides/metabolism
Humans
Brain-Gut Axis
Brain/metabolism

@article {pmid41527783,
year = {2026},
author = {Zülke, AE and Beyer, F and Luppa, M and Mildner, T and Frese, T and Gensichen, J and Kaduszkiewicz, H and Czock, D and König, HH and Wiese, B and Hoffmann, W and Thyrian, JR and Villringer, A and Riedel-Heller, SG and Witte, AV},
title = {Evaluating MRI correlates of lifestyle-based dementia risk reduction: Results from the AgeWell.de imaging study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251414423},
doi = {10.1177/13872877251414423},
pmid = {41527783},
issn = {1875-8908},
abstract = {BackgroundMultidomain lifestyle interventions can improve dementia risk by risk factor modification. Little is known about possible mechanisms underlying this effect.ObjectiveAnalyze whether changes in a validated dementia risk score were linked to changes in neuroimaging markers in a sample of older adults at increased dementia risk, participating in a multimodal lifestyle intervention.MethodsParticipants of the multi-centric AgeWell.de-trial at the Leipzig study site were examined using 3 Tesla MRI at baseline and 24-months follow-up, assessing markers of hippocampal-limbic atrophy and vascular pathology (hippocampal volume (HCV), entorhinal cortex thickness, free water fraction, peak width of skeletonized mean diffusivity, white matter hyperintensity volume, mean gray matter cerebral blood flow). Dementia risk was assessed using the Lifestyle for Brain Health (LIBRA)-index. Multivariable linear regression analyses assessed effects of changes in LIBRA on neuroimaging markers.ResultsOf 56 participants at baseline, 41 underwent the follow-up assessment (Mage: 68.1 (4.1), % female: 46.3, intervention/control group: 16/25). Lower LIBRA-scores, indicating lower dementia risk, were associated with higher HCV at baseline. LIBRA improved in both groups, with no between-group difference in change. Increases in LIBRA were linked to smaller decline in HCV independently of the intervention. No further effects of lifestyle changes on neuroimaging were detected. Exploratory analyses indicated that detrimental lifestyle changes were linked to decreased cognitive performance in the intervention group.ConclusionsWe found no conclusive evidence for associations between lifestyle changes due to a multidomain lifestyle intervention and structural brain health markers. Larger samples and longer interventions may clarify underlying mechanisms.},
}

@article {pmid41527775,
year = {2026},
author = {Teipel, S and König, A and Brem, AK and Perry, G and Moreira, PI and Cole, J and Ferreira, D and Dyrba, M},
title = {Recommendations for reporting findings from analyses using artificial intelligence and machine learning in the Journal of Alzheimer's Disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251413701},
doi = {10.1177/13872877251413701},
pmid = {41527775},
issn = {1875-8908},
abstract = {We propose five recommendations to make AI-based research studies more suitable for a clinical readership. First, authors should justify the added value of complex and potentially more opaque AI approaches. Second, rigorous description of input data, diagnostic criteria, and preprocessing is essential to avoid biased or clinically irrelevant outcomes. Third, benchmarking against clinically relevant performance thresholds should be established a priori. Fourth, method sections should combine an accessible lay summary with detailed technical supplement. Fifth, model explainability is encouraged to mitigate opacity. These recommendations aim to support AI research that is methodologically robust and interpretable for AD researchers.},
}

@article {pmid41527767,
year = {2026},
author = {Harris, M and Bateman, JR and Shaaban, CE and Becker, J and DeKosky, ST and Lopez, OL and Gogniat, MA and Snitz, B and Kaufer, D},
title = {Certainty-weighted recognition memory: Potential applications for early detection and metacognition.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251406623},
doi = {10.1177/13872877251406623},
pmid = {41527767},
issn = {1875-8908},
abstract = {BackgroundMemory loss is a core feature of typical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). Standard memory tests such as word lists assess verbal episodic memory with delayed recall and recognition. However, actual memory fidelity is likely variable, continuous, and has a subjective component.ObjectiveWe investigated dual-processing models of episodic memory (recollection versus familiarity) using confidence ratings in a "judgment of knowing" paradigm (JOK).MethodsThis paradigm was applied to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test as part of neuropsychological evaluation at University of Pittsburgh Alzheimer's Disease Research Center (ADRC), to generate novel indices of memory function to improve sensitivity to early memory problems and provide a memory awareness metric. On recognition testing, participants rated how sure they were of their yes/no responses to each item. We derived novel variables related to memory and metacognition, including an Accuracy-Certainty Index and the Relative Certainty Index.ResultsIn this sample of 347 participants (185 with AD, 55 with MCI, 111 cognitively unimpaired), CERAD Delayed Recall was the best single variable for discriminating groups, although multiple certainty variables also discriminated groups well.ConclusionsThe addition of certainty indices to a standard verbal memory task increased discriminative power between groups, particularly between cognitively normal controls and MCI or AD.},
}

@article {pmid41527760,
year = {2026},
author = {Yang, Y and Kwak, YT},
title = {Neuropsychiatric signs and symptoms clusters and regional amyloid on [18]F-FC119S PET in Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411433},
doi = {10.1177/13872877251411433},
pmid = {41527760},
issn = {1875-8908},
abstract = {BackgroundNeuropsychiatric signs and symptoms (NPS) are highly prevalent in Alzheimer's disease (AD), but whether co-occurring symptom constellations relate to regional amyloid deposition remains unclear.ObjectiveTo identify reproducible NPS clusters in AD and examine their associations with regional amyloid deposition using [18]F-FC119S positron emission tomography (PET).MethodsWe included 143 patients with probable AD and positive amyloid PET. NPS were assessed with the Korean Neuropsychiatric Inventory, and hierarchical cluster analysis (Yule's Q, average linkage) identified symptom clusters. Regional amyloid burden in frontal, temporal, and parietal cortices was quantified by automated SUVRs. Clinical characteristics were compared using t tests, and associations between clusters and regional amyloid patterns were examined with Pearson's χ[2].ResultsFour clusters emerged: Group 1 (delusion, agitation-aggression, disinhibition, aberrant motor behavior); Group 2 (depression, anxiety, irritability); Group 3 (hallucination, euphoria, nighttime behavior, apathy); and Group 4 (eating abnormalities). Group 1 patients were older with worse global status (lower K-MMSE, higher CDR, lower Barthel); Group 2 showed higher GDS15 scores; Group 3 showed selectively lower K-MMSE; Group 4 showed no significant differences. On PET, Group 1 was associated with right frontal and right temporal positivity; Group 2 with left parietal negativity; Group 3 with right frontal positivity plus left parietal negativity; Group 4 showed no significant association.ConclusionsIn amyloid-confirmed, drug-naïve AD, distinct NPS clusters map onto specific regional amyloid patterns and global clinical profiles. These findings support a network-oriented view of NPS pathophysiology and may inform phenotyping and individualized management.},
}

@article {pmid41527759,
year = {2026},
author = {Alkam, T and Tarshizi, E and Van Benschoten, AH},
title = {Flagging high-risk comorbidities in Alzheimer's disease emergency department visits: A machine learning analysis of mortality outcomes.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251409332},
doi = {10.1177/13872877251409332},
pmid = {41527759},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) patients experience elevated mortality during emergency department (ED) encounters, yet the associated risk factors remain insufficiently characterized.ObjectiveTo identify predictors of mortality among older adults with AD during ED visits and examine differences in comorbidity patterns between those who died and those who survived.MethodsWe analyzed 20,532,351 ED visits for adults aged ≥60 from the 2012-2014 Nationwide Emergency Department Sample (NEDS). Visits were stratified by AD status, ZIP-code income quartile, and mortality outcome (defined as in-ED or in-hospital death following ED presentation). We used logistic regression and machine learning models (random forest, gradient boosting, XGBoost) to predict mortality in a 1:1 matched case-control dataset. SHapley Additive exPlanations (SHAP) were applied to interpret model outputs.ResultsAD patients accounted for 1.76-2.13% of all ED visits, with mortality rates of 2.55-2.68% compared to 1.10-1.76% for non-AD patients. Socioeconomic status and ED charges were not associated with increased mortality. Odds ratio analysis identified rare terminal events as top predictors (e.g., respiratory arrest, OR = 55.5), while SHAP analysis highlighted more prevalent and clinically actionable conditions such as acute respiratory failure and septicemia as major drivers of mortality. All models performed comparably (AUC ≈ 0.85).ConclusionsAD patients face significantly higher mortality during ED encounters. Integrating explainable machine learning with large-scale administrative data may help flag lethal comorbidities in real time and improve outcomes through better ED triage and care prioritization.},
}

@article {pmid41527747,
year = {2026},
author = {Heo, RJ and Negida, A and Barrett, MJ and Chrenka, EA and Bayram, E and Kane, JPM and Werner, AM and Rossom, RC and Wyman-Chick, KA},
title = {Cholinesterase inhibitors for patients with dementia: Patterns of prescribing and disparities in treatment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411418},
doi = {10.1177/13872877251411418},
pmid = {41527747},
issn = {1875-8908},
abstract = {BackgroundCholinesterase inhibitors (ChEIs) are cornerstones of the symptomatic treatment of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) and are also prescribed for vascular dementia (VaD). Despite their widespread use, patterns of ChEI prescribing are unclear.ObjectiveOur objective was to examine the prevalence, timing, and types of ChEI prescriptions before and after dementia diagnosis.MethodsWe analyzed electronic health record and claims data for patients diagnosed with AD, DLB, or VaD between October 2015 and August 2022 from a large U.S. healthcare system. ChEI claims (donepezil, rivastigmine, galantamine) were identified in the ±3 years surrounding dementia diagnosis. Repeated measures logistic regression was used to estimate the likelihood of ChEI fills by time-period, dementia type, and time x dementia type interaction to determine if change in prescription patterns significantly differed by diagnosis.ResultsAmong 3166 eligible patients, DLB had the highest prevalence of ChEIs both pre-and post-diagnosis compared to patients with AD and VaD. Post-diagnosis, donepezil was the most common, while galantamine use was sparse. After adjusting for demographics, patients with VaD had lower rates of ChEIs relative to AD (OR: 0.34, 95% CI 0.26-0.45). In the fully adjusted model, females (OR: 0.81, 95% CI: 0.71-0.91) and patients from ethnoracially minoritized populations (OR: 0.74, 95% CI: 0.62-0.88) were less likely to fill ChEI prescriptions.ConclusionsDonepezil was the most frequently filled ChEI across dementias. Patients with DLB had the highest prevalence of ChEIs pre- and post-diagnosis. The potential disparities in treatment we identified should be investigated further.},
}

@article {pmid41527744,
year = {2026},
author = {Wang, X and Ye, T and Dai, B and Zhang, J and Zhou, W and , },
title = {Sex-specific patterns in tau spreading throughout the Braak stages in the Alzheimer's disease spectrum.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251406131},
doi = {10.1177/13872877251406131},
pmid = {41527744},
issn = {1875-8908},
abstract = {BackgroundIncreasing evidence suggests that the trajectory of Alzheimer's disease (AD) pathologies, such as amyloid and tau, differ between the sexes.ObjectiveGiven the higher susceptibility of females to dementia, we aimed to investigate the sex differences in the primary accumulation of tau and its subsequent spread to later cortical brain regions.MethodsWe included 315 participants in this study: 221 cognitively unimpaired individuals with normal amyloid (n = 140, A- CU) or abnormal amyloid (n = 81, A+ CU), and 94 cognitively impaired individuals with abnormal amyloid (A+ CI). Each individual received two to six tau positron emission tomography (PET) scans using the [18F]-Flortaucipir (FTP) tracer. Linear regression analyses were performed to assess sex-specific tau spreading throughout the Braak stages among three clinical groups.ResultsThe median (interquartile range) age of all samples was 73.5 (68 to 78.2) years. In total, 170 participants (54%) were female. In the A+ CU group, females exhibited higher tau-PET SUVR levels in all Braak I, III-IV, and V-VI. We found that the spreading pattern of tau may vary by sex and AD stages. In the A+ CI individuals, there was an observed interaction between the female sex and baseline tau SUVRs in Braak stages III-IV (p < 0.0001 and Bonferroni-corrected p < 0.0023), affecting longitudinal accumulation of tau in later Braak stages V-VI.ConclusionsOur findings found a sex-specific pattern of tau spreading from Braak stages III-IV to V-VI in A+ CI older adults. This disadvantage may indicate that females might experience faster tau spreading and quicker disease progression when the condition develops to more advanced disease stages.},
}

@article {pmid41527739,
year = {2026},
author = {Le, J and Hu, X and Jiang, Y and Wang, Q and Ma, Q and Cui, W},
title = {Insights into phosphoproteomic studies and prospects of phosphoproteins as biomarkers for brain disorders.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411546},
doi = {10.1177/13872877251411546},
pmid = {41527739},
issn = {1875-8908},
abstract = {The dysregulation of phosphorylation networks plays a critical role in the pathogenesis of a wide spectrum of brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, ischemic stroke, drug abuse, major depressive disorder, and schizophrenia. Notably, phosphorylated isoforms of microtubule-associated protein tau and neurofilament heavy polypeptide are already utilized in clinical diagnostics, highlighting the promise of protein phosphorylation signatures as biomarkers for prediction, diagnosis, prognosis, and treatment monitoring. Recent advances in deep phosphoproteomic technologies now facilitate the comprehensive mapping of phosphorylation alterations across diverse biological samples and disease stages. This review summarizes current phosphoproteomic studies aimed at identifying biomarkers for brain disorders and elaborates on the promising application of phosphorylated proteins in this context.},
}

@article {pmid41527736,
year = {2026},
author = {Abedin, MJ and Kastanenka, KV},
title = {The role of astrocytes in Alzheimer's disease: Pathophysiology, biomarkers, and therapeutic potential.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251411561},
doi = {10.1177/13872877251411561},
pmid = {41527736},
issn = {1875-8908},
abstract = {Astrocytes are glial cells in the brain essential for maintaining neural homeostasis, modulating synaptic activity through gliotransmission, and supporting metabolic processes. As part of Alzheimer's disease (AD) progression, astrocytes undergo significant morphological and functional changes, transitioning to reactive states that can contribute to both neuroprotection and neurodegeneration. This review aims to summarize current knowledge on the roles of astrocytes in AD, focusing on their contributions to amyloid-β (Aβ) and tau pathologies, neuroinflammation, disrupted calcium signaling, and age-related changes. We synthesized findings from published studies investigating astrocytic sodium channels (Nav1.6), key molecular pathways such as apolipoprotein E (ApoE), oxidative stress, and excitatory amino acid transporter 2 (EAAT2), as well as emerging astrocytic biomarkers including GFAP, YKL-40, and MAO-B. Optogenetic studies and other experimental approaches with high spatiotemporal resolution were also considered to understand astrocyte involvement in circuit impairments and sleep deficits in AD. Astrocytes in AD exhibit altered calcium signaling, impaired gliotransmission, and dysregulated sodium channel activity. Reactive astrocytes influence Aβ and tau pathology, contribute to neuroinflammation, and show altered biomarker expression. Molecular dysfunctions, including changes in ApoE, EAAT2, and oxidative stress pathways, exacerbate disease progression. Emerging therapeutic strategies targeting astrocytic pathways, such as siRNA therapy and gene editing, show promise for mitigating these pathological changes. Understanding the complex roles of astrocytes in AD highlights their dual protective and detrimental functions and identifies novel avenues for therapeutic intervention. Targeting astrocytic dysfunction may offer strategies to slow disease progression and improve cognitive outcomes.},
}

@article {pmid41527682,
year = {2026},
author = {Zohud, O and Lone, IM and Midlej, K and Iraqi, FA},
title = {The complexity of dementia development and its comorbidities: The collaborative cross-mouse population for multivarious tasks approach.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70131},
pmid = {41527682},
issn = {2576-2095},
support = {//A core fund from Tel Aviv University/ ; },
abstract = {The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge. These conditions have traditionally been studied as isolated central nervous system disorders; however, emerging evidence suggests that broader systemic factors, including chronic inflammation, immune dysregulation, metabolic dysfunction, and genetic susceptibility, may also play a role. This review examines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration. Conditions such as rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation, blood-brain barrier disruption, and neuroinflammatory signaling. Similarly, metabolic disorders such as diabesity promote insulin resistance and oxidative stress, accelerating cognitive decline. The review also discusses glaucoma as a neurodegenerative condition with autoimmune features, underscoring the need for expanded classification and treatment strategies. A key focus is the utilization of the Collaborative Cross (CC) mouse model, which enables the study of gene-environment interactions across genetically diverse backgrounds. Findings from CC mice reveal strain-dependent susceptibility to inflammation, cognitive impairment, and gut-brain axis dysfunction, providing a translational bridge to human variability. This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences. Advancing our understanding of these multiorgan interactions holds potential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.},
}

@article {pmid41527663,
year = {2025},
author = {Barbati, SA and Carota, G and Partsinevelos, K and Di Pietro, L and Privitera, A and Cardaci, V and Graziani, A and Mangione, R and Lazzarino, G and Tavazzi, B and Di Pietro, V and Maiani, E and Bellia, F and Amorini, AM and Lazzarino, G and Baba, SP and Caruso, G},
title = {Preclinical evidence and therapeutic perspectives on carnosine for the treatment of neurodegenerative disorders.},
journal = {AIMS neuroscience},
volume = {12},
number = {4},
pages = {444-513},
doi = {10.3934/Neuroscience.2025025},
pmid = {41527663},
issn = {2373-7972},
abstract = {Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely distributed in mammalian tissues, especially skeletal and cardiac muscle cells, and, to a lesser extent, in the brain. While early interest in carnosine was given because of its role in muscle cell metabolism and athletic performance, it has more recently gained attention for its potential application in several chronic diseases. Specifically, brain aging and neurodegenerative disorders have received particular attention, as a marked reduction in carnosine levels has been described in these conditions. Carnosine exerts a wide range of biological activities, including antioxidant, anti-inflammatory, anti-glycation, metal-chelating, and neuroprotective properties. Mechanistically, it acts by inhibiting the production of advanced glycation end products (AGEs), buffering cellular pH, and regulating intracellular nitric oxide signaling and mitochondrial function. Its safety profile, the lack of toxicity, and significant side effects support its application for long-term therapeutic use. In this review, we aim to recapitulate and discuss the effects, dosages, and administration routes of carnosine in preclinical in vivo models, with a particular focus on neurodegenerative disorders where it has been shown to reduce oxidative stress, suppress neuroinflammation, modulate protein aggregation, and preserve cognitive function, all key features of neurodegeneration. Despite promising findings, there are gaps in the knowledge on how carnosine affects synaptic plasticity, neuronal remodeling, and other processes that play a central role in the pathophysiology of neurodegenerative disorders. Additionally, clinical translation remains challenging due to inconsistencies across in vivo studies in terms of dosage, treatment duration, routes of administration, and disease models, which affect reproducibility and cross-study comparability. Therefore, while carnosine emerges as a multifunctional and well-tolerated molecule, further research is needed to clarify its therapeutic relevance in human diseases. In this review, we also address future perspectives and key methodological challenges that must be overcome to effectively translate carnosine's biological potential into clinical practice.},
}

@article {pmid41527522,
year = {2026},
author = {Richardson, TI and Klein, RC and Huang, K and Zhang, J and Mesecar, AD and Dage, JL and Clayton, B and Lamb, BT and Palkowitz, AD},
title = {Next-generation Alzheimer's therapeutics: target assessment and enablement at the Indiana University School of Medicine-Purdue University TREAT-AD Center.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70964},
doi = {10.1002/alz.70964},
pmid = {41527522},
issn = {1552-5279},
support = {U54AG065181/AG/NIA NIH HHS/United States ; },
mesh = {*Alzheimer Disease/drug therapy ; Humans ; *Drug Discovery/methods ; Indiana ; United States ; National Institute on Aging (U.S.) ; Schools, Medical ; },
abstract = {The incidence of Alzheimer's disease (AD) continues to increase, despite decades of effort to develop disease-modifying therapies. In response, the National Institute on Aging (NIA) established the TaRget Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) centers to address the gap between basic research and translational drug discovery. Situated within a robust AD research environment, the Indiana University School of Medicine (IUSM)-Purdue University TREAT-AD Center is one of two National Institutes of Health (NIH)-supported centers funded to accomplish this mission. With a focus on novel biological targets beyond amyloid and tau, our center has assembled the necessary components of a drug discovery engine: project and data management, bioinformatics and computational science, structural biology and biochemistry, assay development and pharmacology, and molecular design and synthesis of small molecules, antibodies, and oligonucleotides. Our objective is to deliver Target Enabling Packages (TEPs) within an open science framework, making data, methods, and research tools broadly accessible through the AD Knowledge Portal. HIGHLIGHTS: The Indiana University School of Medicine (IUSM)-Purdue TREAT-AD Center develops Target Enabling Packages (TEPs) to advance novel targets for the treatment of Alzheimer's disease (AD). The center is overseen by an administrative core and operates through four technical cores - bioinformatics, structural biology, assay development, and medicinal chemistry - within a milestone-driven and open science framework. Multi-omics, systems biology, and machine learning (ML) approaches guide the nomination of high-priority targets beyond amyloid and tau. Cross-core workflows provide structural insights into novel biological targets, validated assays, biomarkers, and molecular probes that enable lead optimization. All data, methods, and tools are openly shared through the AD Knowledge Portal to accelerate global efforts in AD drug discovery.},
}

*Alzheimer Disease/drug therapy
Humans
*Drug Discovery/methods
Indiana
United States
National Institute on Aging (U.S.)
Schools, Medical

@article {pmid41527496,
year = {2026},
author = {Kalita, T and Shakya, A and Ghosh, SK and Singh, UP and Bhat, HR},
title = {Microwave-Assisted Synthesis and In Vitro Anti-Alzheimer Evaluation of Novel 1,3,5-Triazine-Nicotinic Hydrazide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {1},
pages = {e70685},
doi = {10.1002/jbt.70685},
pmid = {41527496},
issn = {1099-0461},
mesh = {*Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry ; *Butyrylcholinesterase/metabolism/chemistry ; *Alzheimer Disease/drug therapy/enzymology ; *Acetylcholinesterase/metabolism/chemistry ; Animals ; Humans ; *Triazines/chemistry/pharmacology/chemical synthesis ; *Microwaves ; Cell Line, Tumor ; Molecular Docking Simulation ; Male ; *Hydrazines/chemistry/pharmacology/chemical synthesis ; Rats ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder posing major global health challenges due to its complex pathophysiology and increasing prevalence among the elderly. In the present work, the molecular hybridization technique was utilized to design and synthesize nicotinic hydrazide-1,3,5-triazine hybrids. Accordingly, this study aimed to design, perform in silico screening, synthesize, and evaluate the in vitro and in vivo anti-AD potential of the proposed compounds. Docking studies revealed that the compounds displayed key interactions with catalytic site and peripheral anionic site residues. Based on binding affinity, ten compounds were synthesized and characterized using different spectroscopic techniques. In vitro AChE and BChE inhibitory assays revealed that the compound 4A36 showed the highest inhibitory ability with log IC50 values of 5.97 μM against AChE and 4.57 μM against BChE. In addition, cytotoxicity screening revealed that 4A36 was non-toxic in SH-SY5Y neuroblastoma cells in the concentration range of 15.625-250 µg/mL. Acute oral toxicity evaluation of the compound revealed no adverse effects up to 175 mg/kg b.w. Further, in vivo studies using the scopolamine-induced model further validated the therapeutic promise of the compound. At a dose of 30 mg/kg b.w., the compound demonstrated significant improvements in learning and memory, reduced MDA levels with concurrent elevation of antioxidant enzymes SOD and Catalase, and reduced AChE activity in hippocampal tissue. Histopathological observations revealed that treatment groups, especially at higher dose (30 mg/kg b.w.), preserved the granular layer of the dentate gyrus and improved neuronal integrity compared to the disease control. These findings indicate that 4A36 at a dose of 30 mg/kg b.w. may be considered as a promising lead compound in AD.},
}

*Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry
*Butyrylcholinesterase/metabolism/chemistry
*Alzheimer Disease/drug therapy/enzymology
*Acetylcholinesterase/metabolism/chemistry
Animals
Humans
*Triazines/chemistry/pharmacology/chemical synthesis
*Microwaves
Cell Line, Tumor
Molecular Docking Simulation
Male
*Hydrazines/chemistry/pharmacology/chemical synthesis
Rats

@article {pmid41527485,
year = {2026},
author = {Cheng, Q and Nolz, J and Karr, T and Dorn, N and Readhead, B and Krajmalnik-Brown, R and Mastroeni, D},
title = {Gut proteome and microbiome alterations: Analysis of transverse colon samples from pathologically confirmed Alzheimer's disease patients.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71021},
doi = {10.1002/alz.71021},
pmid = {41527485},
issn = {1552-5279},
support = {U24 NS072026/NS/NINDS NIH HHS/United States ; P30AG19610//the National Institute on Aging/ ; P30AG072980//the National Institute on Aging/ ; 211002//the Arizona Department of Health Services/ ; 4001//the Arizona Biomedical Research Commission/ ; 0011//the Arizona Biomedical Research Commission/ ; 05-901//the Arizona Biomedical Research Commission/ ; and 1001//the Arizona Biomedical Research Commission/ ; //the Michael J. Fox Foundation for Parkinson's Research/ ; //Arizona Alzheimer's Consortium/ ; //Biodesign Center for Health Through Microbiomes/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Proteome/metabolism ; Female ; Male ; *Colon/microbiology/metabolism/pathology ; Aged ; Proteomics ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) has been regarded as a brain-first disorder. Emerging evidence suggests that the gut may influence central nervous system pathology, but the mechanisms remain unclear.

METHODS: We conducted a proteomic and microbial analysis of transverse colon samples from clinically and pathologically confirmed AD and control cases.

RESULTS: In the AD gut samples, antimicrobial humoral response and oxidative stress response were downregulated, while catabolic processes and insulin signaling were upregulated. Several complement (e.g., C5) and synaptic (e.g., synaptophysin) proteins were downregulated. Amyloid beta 42 was detected at higher levels. Christensenellaceae, Desulfovibrio, and Candida tropicalis amplicon sequence variants were higher in abundance, while Streptococcus, Lachnospiraceae, Blautia, and Nakaseomyces were lower. In general, bacterial composition correlated with AD clinical variables such as plaque and tangle burden.

DISCUSSION: These findings underscore the gut's possible involvement in AD pathogenesis and provide new insights into potential biomarkers and therapeutic targets.

HIGHLIGHTS: This study provides the first in-depth analysis of the proteome and microbiome in AD transverse colon tissues. Multiple immune and oxidative stress response pathways were downregulated in AD, while metabolic pathways were upregulated. Synaptic protein, complement protein, and Aβ42 levels were significantly different between AD and controls. Transverse colon microbial composition was associated with AD clinical variables.},
}

Humans
*Alzheimer Disease/pathology/microbiology/metabolism
*Gastrointestinal Microbiome/physiology
*Proteome/metabolism
Female
Male
*Colon/microbiology/metabolism/pathology
Aged
Proteomics
Aged, 80 and over
Amyloid beta-Peptides/metabolism

@article {pmid41527161,
year = {2026},
author = {Cheng, CM and Tsai, MJ and Tseng, CC and Lin, YS and Lin, YS and Chen, LY and Liu, MN and Fuh, JL},
title = {Pharmacological management of agitation in dementia: An evidence-based review with expert consensus.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001342},
pmid = {41527161},
issn = {1728-7731},
abstract = {Agitation is a frequently occurring and challenging neuropsychiatric symptom of Alzheimer's disease (AD) that substantially affects quality of life, caregiver burden, and healthcare utilization. Non-pharmacological interventions, especially trigger identification, environmental adjustments, and supportive activities, remain the first-line approach for treating agitation. Pharmacological treatment should be considered only when non-drug measures are insufficient or when agitation causes severe distress or safety risks. This consensus integrates evidence up to June 2025, the Taiwan Ministry of Health and Welfare approvals, and Taipei Veterans General Hospital expert opinion. Among the approved agents, brexpiprazole demonstrated the strongest evidence and most favorable safety profile. Risperidone and aripiprazole are effective, but require careful monitoring for cerebrovascular and extrapyramidal risks. Selected antidepressants, particularly citalopram and agomelatine, should be considered when safety is prioritized. Anticonvulsants, acetylcholinesterase inhibitors, and memantine have limited efficacy and should be reserved for refractory cases. Long-term or routine pharmacological use is not supported by current evidence. Future research should focus on identifying responsive patient subgroups, optimizing dosing strategies, and integrating medications into individualized, multidisciplinary care plans.},
}

@article {pmid41527104,
year = {2026},
author = {Chen, H and Li, N and Liu, N and Zhu, H and Ma, C and Ye, Y and Shi, X and Luo, G and Dong, X and Tan, T and Wei, X and Yin, H},
title = {Correction: Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP/PS1 mouse model of Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {7},
pmid = {41527104},
issn = {1758-9193},
}

@article {pmid41527082,
year = {2026},
author = {Du, Y and Wu, L and Mao, Y and Chen, S and Gao, X},
title = {IL-27, a metabolic regulator secreted by astrocytes in response to GLP-1RA OHP2, modulates microglial reprogramming in Alzheimer's disease by regulating cGAS lactylation.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03683-1},
pmid = {41527082},
issn = {1742-2094},
support = {82473834//National Natural Science Foundation of China,China/ ; 82373780//National Natural Science Foundation of China,China/ ; CPU2022PZQ10//"Double First-Class" University Project/ ; },
}

@article {pmid41527012,
year = {2026},
author = {Weber, C and Wind, D and Petzsch, P and Supprian, T and Dilthey, A and Christl, J and Finzer, P},
title = {Dysbiotic shift in the oral microbiota of patients with Alzheimer's disease compared to their healthy life partners-a combinatorial approach and a paired study design.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-025-01941-1},
pmid = {41527012},
issn = {1758-9193},
abstract = {BACKGROUND: The oral microbiota has been associated with Alzheimer's disease (AD). However, earlier studies provided conflicting results using varying sampling methods, sequencing techniques, and statistics, as well as independent subjects.

METHODS: To robustly identify disease-associated microbial features, we recruited patients and their healthy life partners from the same households sharing a more similar microbiota compared to independent individuals increasing statistical power via paired design and combined three different sequencing methods - including metagenomics-and several bioinformatic pipelines. We recruited 26 AD-patients and their life partners. Salivary and supragingival samples were collected and a clinical examination of the mouth was performed.

RESULTS: Both groups showed comparable oral health. By focusing primarily on recurrently identified species across the different datasets we were able to identify a Core dysbiosis. This Core dysbiosis surprisingly spares the most central of oral diseases pathogens, namely Porphyromonas gingivalis. However, it includes numerous other species commonly associated with oral pathologies such as Prevotella nigrescens, Streptococcus anginosus, Dialister invisus, Anaeroglobus geminatus, Olsenella uli and Mogibacterium timidum. In contrast, more host-compatible species such as Prevotella melaninogenica or Streptococcus parasanguinis are identified in controls.

CONCLUSIONS: This is the first study using a combined sequencing approach and a paired study design to identify robust features of the oral microbiota of AD-patients. Although promising, the results should nevertheless be interpreted with caution, as the cross-sectional study design limits the possibilities of interpretation, and larger, longitudinal data are necessary for causal conclusions. However, this combined approach on multiple processing levels to identify intra-partnership differences still offers the possibility to better identify disease-associated microbial features potentially involved in AD-pathogenesis.

TRIAL REGISTRATION: This study was prospectively registered at the German Clinical Trials Register (DRKS00023456) at the 30th of November 2020.},
}

@article {pmid41526986,
year = {2026},
author = {Fu, X and Cai, H and Quan, S and Zhang, W and Geng, Y and Tian, Q and Ren, Z and Xu, Y and An, C and Li, J and Chu, C and Wang, W and Pang, Y and Wang, Q and Lu, L and Wang, Q and Li, Y and Li, F and Nie, S and Jia, L},
title = {Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00927-3},
pmid = {41526986},
issn = {1750-1326},
support = {81870825, 82071194//National Natural Science Foundation of China/ ; Z201100005520016//Beijing Brain Initiative from Beijing Municipal Science & Technology Commission/ ; 7202061//Beijing Municipal Natural Science Foundation/ ; 2022-2-2017//Capital's Funds for Health Improvement and Research/ ; 2022ZD0211600, 2022ZD0211605//STI2030-Major Projects/ ; },
abstract = {BACKGROUND: Complement dysregulation is increasingly recognized in Alzheimer's disease (AD). However, the temporal profile of complement alterations preceding AD onset and their distinction from age-related immune changes remain poorly defined. Clarifying these dynamics could provide insights into AD pathogenesis and identify systemic factors that predict disease onset and progression.

METHODS: We conducted a study involving two cohorts: a longitudinal cohort (n = 235; all cognitively normal at baseline) and a cross-sectional cohort (n = 323; including 53 with AD, 54 with vascular dementia, 51 with Parkinson's disease dementia, 56 with behavioral variant frontotemporal dementia, and 52 with dementia with Lewy bodies). Plasma levels of 14 complement factors were assessed every 2 years over a 10-year follow-up period in the longitudinal cohort and once in the cross-sectional cohort.

RESULTS: In the longitudinal cohort, aging was accompanied by gradual reductions in C4, C4b, Factor I, and Properdin and by increases in Factor D. These changes were more pronounced in individuals who subsequently developed AD. Importantly, this pattern of complement alterations was detectable during the preclinical and clinical phases of AD but was not observed in other dementias. In the cross-sectional cohort, the same complement profile was specific to AD and distinguished it from other dementia subtypes.

CONCLUSIONS: The results of this study indicate an AD-specific peripheral complement signature associated with disease development, highlighting complement factors as critical immune mediators that link aging and AD. This signature implicates complement factors as promising systemic markers for early detection and potential therapeutic targeting in preclinical AD.},
}

@article {pmid41526743,
year = {2026},
author = {},
title = {CDK3 drives neuron loss in Alzheimer's disease.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {41526743},
issn = {2662-8465},
}

@article {pmid41526727,
year = {2026},
author = {Mei, Y and Zheng, L and He, M and Wang, L and Zhou, Y and Zhang, T and Lee, TH and Chen, D},
title = {Zipper-interacting Protein Kinase Modulates Gene Expression Linked to Synaptic and Neuronal Processes after Traumatic Brain Injury.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {358},
pmid = {41526727},
issn = {1559-1182},
support = {82001128//National Natural Science Foundation of China/ ; 82571556//National Natural Science Foundation of China/ ; 82571601//National Natural Science Foundation of China/ ; 2023Y9007//Joint Funds for the Innovation of Science and Technology, Fujian Province/ ; 2024Y9094//Joint Funds for the Innovation of Science and Technology, Fujian Province/ ; 2024J01485//Natural Science Foundation of Fujian Province/ ; },
mesh = {Animals ; *Brain Injuries, Traumatic/genetics/pathology/enzymology ; *Neurons/metabolism/pathology ; *Synapses/metabolism/genetics ; Mice, Inbred C57BL ; *Gene Expression Regulation ; Male ; Mice ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Signal Transduction/genetics ; },
abstract = {Traumatic brain injury (TBI) is one of the leading causes of disability and death worldwide. Zipper-interacting protein kinase (ZIPK) is a serine/threonine kinase, whose main function is to regulate cell death, inflammation and smooth muscle contraction. ZIPK dysregulation has been implicated in a range of neurological disorders, including ischemic stroke, Alzheimer's disease, and TBI. Downregulation of ZIPK expression level or pharmacological inhibition of ZIPK kinase activity alleviates neuronal injury. ZIPK has a nuclear localization signal sequence and transcriptional regulatory activity. However, whether ZIPK affects gene expression in the brain after TBI remains unknown. In this study, transcriptome sequencing analysis was employed to compare the differences in gene expression in the peri-injury tissues between wild-type and ZIPK heterozygous mice after TBI. Our results indicated that ZIPK regulates a variety of genes and signaling pathways, including pathways related to synaptic function, learning and memory, vascular function, and DNA replication, after TBI. Gene set enrichment analysis highlighted the important role of ZIPK in synapses during TBI. In addition, quantitative real-time PCR analysis validated changes in the expression of multiple genes related to synaptic function, including Drd1, Grin2a, Grin2b, Dlg4, Fn1, and Pecam1, which were identified by gene correlation analysis and protein-protein interaction analysis. Immunofluorescence staining revealed that partial deletion of ZIPK alleviates synaptic protein loss induced by TBI. In conclusion, our data suggest a role for ZIPK in the regulatory network in the brain, especially in relation to synaptic damage, after TBI, providing a new therapeutic strategy for this condition.},
}

Animals
*Brain Injuries, Traumatic/genetics/pathology/enzymology
*Neurons/metabolism/pathology
*Synapses/metabolism/genetics
Mice, Inbred C57BL
*Gene Expression Regulation
Male
Mice
*Protein Serine-Threonine Kinases/metabolism/genetics
Signal Transduction/genetics

@article {pmid41526725,
year = {2026},
author = {Li, R and Berlowitz, D and Mez, J and Silver, B and Wang, X and Hu, W and Goodwin, R and Keating, H and Liu, W and Lin, H and Yu, H},
title = {Early prediction of Alzheimer's disease using longitudinal electronic health records of US military veterans.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {23},
pmid = {41526725},
issn = {2730-664X},
abstract = {BACKGROUND: Early prediction of Alzheimer's disease is important for timely intervention and treatment. We examine whether machine learning on longitudinal electronic health record notes can improve early prediction of Alzheimer's disease.

METHODS: From Veterans Health Administration records (2000 to 2022), we studied 61,537 individuals diagnosed with Alzheimer's disease and 234,105 without, aged 45-103 years, 98.4% were male. From clinical notes, we quantified the frequency of subjective cognitive decline and Alzheimer's disease-related keywords, and applied statistical machine learning models to assess their ability to predict future diagnosis.

RESULTS: Here we show that Alzheimer's-related keywords (e.g., "concentration," "speaking"), occur more often in notes of individuals who later develop Alzheimer's disease than in controls. In the 15 years preceding diagnosis, cases demonstrate an exponential increase in keyword mentions (from 9.4 to 57.7 per year), whereas controls show a slower, linear increase (8.2 to 20.3). These trends are consistent across demographic subgroups. Random forest models using these keywords for prediction achieve an area under receiver operating characteristic curve from 0.577 at ten years before diagnosis to 0.861 one day before diagnosis, consistently outperforming models using only structured data.

CONCLUSIONS: Signs and symptoms of early Alzheimer's disease are reported in clinical notes many years before a clinical diagnosis is made and the frequency of these signs and symptoms, approximated by keywords, increases the closer one is to the diagnosis. A simple keyword-based approach can capture these signals and can help identify individuals at high risk of future Alzheimer's disease.},
}

@article {pmid41526711,
year = {2026},
author = {Sheng, J and Yang, Z and Wang, Y and Zhang, Q and Xin, Y and Song, Y and Wang, L},
title = {Metabolism fluctuation coupling can track the progression of dementia and describe MST1 gene-related pathology.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {24},
pmid = {41526711},
issn = {2730-664X},
support = {62271177//National Natural Science Foundation of China (National Science Foundation of China)/ ; LZ24F01007//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; },
abstract = {BACKGROUND: Cognitive resilience refers to an individual's capacity to cope with brain aging and pathology and to delay cognitive decline, whereas existing techniques such as functional magnetic resonance imaging capture only macroscopic features without linking them to neurophysiological mechanisms. Recent studies have shown that overexpression of the MST1 gene exacerbates Alzheimer's disease phenotypes by affecting neuronal activity and metabolism; however, its association with cognitive trajectories and imaging biomarkers remains to be further investigated.

METHODS: Multimodal imaging data using information from 116 individuals with mild cognitive impairment was obtained from the ADNI database and participants from the HABS database. The correlation coefficient between glucose metabolism and neuronal low-frequency fluctuations was calculated, and residuals were derived from regression models of correlation coefficient with amyloid protein. Unsupervised clustering was then applied, and mediation analysis was conducted to investigate the mediating role of limbic orbital frontal cortex residuals in the association between MST1 gene expression and cognitive trajectories.

RESULTS: Clustering identifies five groups with distinct cognitive trajectories: the high and low cognitive resilience groups exhibit slower dementia progression with lower MST1 expression, whereas the high and low cognitive vulnerability groups show faster dementia progression with higher MST1 expression. No significant differences are observed in glucose metabolism or amyloid protein levels across groups, while the limbic orbital frontal cortex residuals partially mediate the effect of MST1 gene expression on cognitive trajectories.

CONCLUSIONS: Residual biomarkers can track dementia progression and characterize MST1-related pathology, providing imaging markers for assessing cognitive resilience and monitoring disease at the molecular level.},
}

@article {pmid41526632,
year = {2026},
author = {Salajková, Z and Ciasca, G and Di Lorenzo, F and Ghoreishi, M and Reale, R and Gambarota, MG and Zhang, J and Zhang, Y and Ricco, V and Ruocco, G and Leonetti, M},
title = {Non-invasive screening of alzheimer's disease via label-free tri-spectral retinal imaging.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35383-y},
pmid = {41526632},
issn = {2045-2322},
support = {No. 855923/ERC_/European Research Council/International ; No. 855923/ERC_/European Research Council/International ; CUP J33C22001130001//NextGenerationEU PNRR MUR- M4C2-Action/ ; No. 101098989//European Innovation Council/ ; CUP: 2022CFP7RF//MUR PRIN 2022/ ; CUP: 2022CFP7RF//MUR PRIN 2022/ ; },
abstract = {Alzheimer's disease (AD) is the most prevalent form of dementia, yet its early detection remains challenging due to the invasiveness, cost, and limited accessibility of current diagnostics. Increasing evidence suggests that retinal changes mirror cerebral pathology in AD, making the eye a promising site for non-invasive biomarker discovery. Here, we present a technique employing a custom-built tri-spectral retinal imaging module, designed to be integrated with existing fundus imaging systems, that captures retinal reflectance across three optimized spectral bands to quantify spectral alterations linked to AD. We validate the system in a case-control study of 38 mild AD patients and 28 age-matched controls, revealing spatially resolved differences in a fundus map derived from the blue-to-green ratiometric channel (p < 0.001). Our analysis identifies specifically the fovea-to-optic disc region as the most discriminative for AD, with an AUC of 0.74. Building on this, we developed a biologically informed machine-learning classification model incorporating spectral, clinical, and demographic data. On an independent validation test, the model achieved an AUC of 0.91, matching or slightly outperforming the most advanced spectral retinal measurements, yet using a simpler, more stable, and cost-effective setup that further facilitates clinical translation. The demonstrated technology, thanks to its non-invasiveness and its integrability with both existing medical technologies and advanced quantitative statistical methods, holds the potential to drive a significant leap forward in the early detection of AD, opening a window for timely intervention and thus profoundly impacting patient care.},
}

@article {pmid41526594,
year = {2026},
author = {Fisher, DW and Fisher, JR and Urfer, SR and Tran, NA and Kerr, KF and , and Darvas, M},
title = {Higher burden of neuropsychiatric symptom-like behaviors associated with canine cognitive dysfunction compared to normal aging in the Dog Aging Project.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41526594},
issn = {2509-2723},
abstract = {Non-cognitive, neuropsychiatric symptoms (NPS) are nearly universal in Alzheimer's disease (AD), but investigation of their underlying biology is complicated by comparative medicine approaches that incompletely capture spontaneous disease, primarily using transgenic rodent models. The aged companion dog, which spontaneously develops an AD-like disease called canine cognitive dysfunction (CCD), may help fill this translational gap. Using data from the Dog Aging Project with > 10,000 aged dogs (> 8 years old), we identify numerous behaviors in dogs "at-risk" for and with CCD that mirror NPS in humans. Compared to dogs without CCD, our analysis shows that dogs with CCD are less physically active, exhibit fewer previously trained behaviors, demonstrate fewer motivated behaviors, have more daytime sleep, demonstrate more separation anxiety, have altered anxious responses to novelty, have changes in aggressive behaviors, and exhibit lower appetite. Using k-means clustering, we did not find evidence for behavioral sub-phenotypes. Overall, our analysis of a large number of aged dogs suggests clinically significant NPS are associated with CCD and that the companion dog may serve as an important comparative medicine approach to understand these debilitating symptoms across species.},
}

@article {pmid41526552,
year = {2026},
author = {Wang, W and Zhu, H and Jiang, Q and Shi, Y and Wang, X},
title = {FOXO: a key target in regulating aging and age-related diseases.},
journal = {Biogerontology},
volume = {27},
number = {1},
pages = {38},
pmid = {41526552},
issn = {1573-6768},
support = {202301BA070001-046 and 202401BA070001-090//the Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities' Association/ ; },
mesh = {Humans ; *Aging/metabolism/genetics ; Animals ; *Forkhead Transcription Factors/metabolism ; Oxidative Stress ; Autophagy ; *Neurodegenerative Diseases/metabolism ; Signal Transduction ; },
abstract = {FOXOs constitute a class of evolutionarily conserved transcription factors that play pivotal roles in diverse cellular processes, including glucose and lipid metabolism, energy homeostasis, oxidative stress response, and autophagy. They are recognized as central regulators of longevity. This review details the mechanisms linking FOXO to aging. FOXO activity is regulated via nucleocytoplasmic shuttling, a process controlled by phosphorylation and dephosphorylation through the insulin/insulin-like growth factor (IIS) signaling pathway. This shuttling influences the expression of aging-related genes, thereby modulating aging-related phenotypes in tissues such as muscle and liver. Furthermore, FOXO can also regulate the autophagy pathway through multiple mechanisms: On one hand, it transcriptionally activates core autophagy genes such as Ulk2 and Becn1; on the other hand, it enhances autophagic activity by modulating miRNAs or epigenetic modifications, thereby promoting the elimination of damaged cellular components, and ultimately delaying organismal aging. Moreover, as a key sensor of oxidative stress, FOXO is activated by reactive oxygen species (ROS), thereby inducing the expression of antioxidant enzymes that mitigate oxidative damage and delay cellular aging. This review provides an in-depth exploration of the dual roles of FOXO in various aging-related diseases. This includes neurodegenerative diseases (such as Huntington's disease, Parkinson's disease, and Alzheimer's disease), metabolic disorders (such as type 2 diabetes), and various cancers. Meanwhile, this review also discusses drugs targeting the FOXO pathway in recent years (such as canagliflozin, metformin, resveratrol, and berberine). These FOXO-targeting compounds demonstrate great potential in improving metabolic disorders and delaying the onset of aging phenotypes.},
}

Humans
*Aging/metabolism/genetics
Animals
*Forkhead Transcription Factors/metabolism
Oxidative Stress
Autophagy
*Neurodegenerative Diseases/metabolism
Signal Transduction

@article {pmid41526199,
year = {2026},
author = {Iwamoto, S and Hatta, D and Fujii, M and Yamamoto, D and Ohta, R and Okita, K and Shirotani, K and Iwata, N},
title = {Cell type- and neuronal differentiation-dependent MME 5'UTR splice variants with distinct translational outputs in human cells.},
journal = {Journal of biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1093/jb/mvag002},
pmid = {41526199},
issn = {1756-2651},
abstract = {Neprilysin (NEP) is a major enzyme that degrades amyloid β-peptide (Aβ) in the brain. Deficient NEP activity causes Aβ to accumulate, leading to amyloid pathology in Alzheimer's disease. Transcripts from the MME gene encoding NEP comprise seven splice variants (v1, v1bis, v2a, v2b, and v3-5) with different structures in the 5'-untranslated region. We analyzed the expression levels of MME variants in neuronal and non-neuronal cells using real-time PCR and investigated their translational outputs using cells co-transfected with cDNAs of each MME variant and green fluorescent protein. v1 and v1bis were constitutively expressed as major components in both cell types, whereas v2b was preferentially expressed in non-neuronal cells. The translational outputs of v1 and v2b were similar to each other and much higher than those of the other variants. Retinoic acid-induced neuronal differentiation altered the compositional ratios of MME variants and transiently enhanced their translational outputs, which declined in a variant-specific manner with further differentiation. We demonstrated that MME variants show cell type-dependent expression and distinct translational outputs that are sensitive to retinoic acid. Further studies are required to elucidate the molecular mechanisms underlying the post-translational roles of MME variants, such as subcellular localization and local translation.},
}

@article {pmid41525887,
year = {2026},
author = {Draper, D and George, AE and Veenendaal, T and van Dijk, S and Soltani, E and Sanzà, P and Verweij, FJ and Klumperman, J and Farías, GG},
title = {HOPS disruption impairs APP trafficking and processing, promoting exosomal secretion of APP-CTFs.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107269},
doi = {10.1016/j.nbd.2026.107269},
pmid = {41525887},
issn = {1095-953X},
abstract = {Amyloid precursor protein (APP) is a key player in various neuronal functions but also the source for toxic Aβ that accumulates in the brain of Alzheimer patients. APP trafficking and processing depend on the endo-lysosomal system, but the molecular mechanisms that coordinate these processes remain not fully understood. Here, we studied the HOPS complex, a central regulator of endo-lysosomal maturation. We show that HOPS disruption impairs retromer-mediated recycling of APP to the TGN, resulting in the accumulation of APP in late endosomes. In neurons, this accumulation is spatially restricted to somatodendritic endosomes. These APP-containing endosomes are catalytically inactive and lack the γ-secretase subunit PSEN2. However, they do contain BACE1, which contributes to the build-up of toxic APP C-terminal fragments (APP-CTFs). Notably, loss of HOPS function enhances secretion of APP-CTFs by exosomes, suggesting a potential mechanism for disease propagation. Together, our findings establish a mechanistic link between HOPS loss-of-function and aberrant APP processing, with implications for neurodegeneration.},
}

@article {pmid41525885,
year = {2026},
author = {Nagarajan, V and Libowitz, CL and Ackley, BD and Wolfe, MS},
title = {A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107267},
doi = {10.1016/j.nbd.2026.107267},
pmid = {41525885},
issn = {1095-953X},
abstract = {The membrane-embedded γ-secretase complex is involved in the intramembrane cleavage of ~150 substrates. Cleavage of amyloid precursor protein (APP)-derived substrate C99 generates 38-43-residue secreted amyloid β-peptides (Aβ), with the aggregation-prone 42-residue form (Aβ42) particularly implicated in the pathogenesis of Alzheimer's Disease (AD). However, whether Aβ42 is the primary driver of neurodegeneration in AD remains unclear. Dominant mutations in APP or presenilin-the catalytic component of γ-secretase-cause early-onset familial AD (FAD) and reduce one or more steps in the multi-step processive proteolysis of C99 to Aβ peptides, apparently through stabilization of γ-secretase enzyme-substrate (E-S) complexes. To investigate mechanisms of neurodegeneration in FAD, we developed new C. elegans models co-expressing wild-type or FAD-mutant C99 substrate and presenilin-1 (PSEN1) variants in neurons, allowing intramembrane processing of C99 to Aβ in vivo. We demonstrate that while FAD-mutation of either C99 or PSEN1 leads to age-dependent synaptic loss, proteolytically inactive PSEN1 did not. Designed mutations that allow stable E-S complex formation without Aβ42 or Aβ production likewise result in synaptic degeneration. Moreover, replacement of C99 with variants of a Notch1-based substrate revealed that disrupted processing of another γ-secretase substrate can similarly lead to synaptic degeneration. These results support a model in which synaptic loss can be triggered by toxic, stalled γ-secretase E-S complexes in the absence of Aβ production and not by simple loss of proteolytic function. This new C. elegans system provides a powerful platform to study the role of dysfunctional γ-secretase substrate processing in FAD pathogenesis.},
}

@article {pmid41525820,
year = {2026},
author = {Mateo, D and Souza, MCO and Carrión, N and Heredia, L and Cabrera, C and Marquès, M and Forcadell, E and Pino, M and Zaragoza, J and Domingo, JL and Barbosa, F and Torrente, M},
title = {Elevated fecal silver, lithium, and platinum in cognitive impairment: A pilot exploration of microbiota-metal interactions.},
journal = {Neurotoxicology},
volume = {},
number = {},
pages = {103390},
doi = {10.1016/j.neuro.2026.103390},
pmid = {41525820},
issn = {1872-9711},
abstract = {BACKGROUND: Gut microbiota (GMB) and metal exposure have both been implicated in cognitive impairment (CI), including amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). However, studies integrating these areas remain scarce.

OBJECTIVE: This pilot study aimed to investigate whether exposure to metals modulates the relationship between GMB composition and clinical outcomes in individuals with CI.

METHODS: Stool samples were collected from aMCI (n = 12), AD (n = 18), and cognitively healthy controls (HC, n = 30). Participants were categorized into CI (n = 30) and HC (n = 30). Gut microbial diversity was assessed using shotgun sequencing, and 25 metals were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive, neuropsychological, neuropsychiatric, and functional assessments were also conducted.

RESULTS: No significant differences were observed between groups in microbial richness, alpha-diversity (Shannon index), or beta-diversity (Bray-Curtis). Likewise, microbial diversity measures were not associated with cognitive outcomes. In contrast, aMCI and AD participants exhibited significantly higher fecal concentrations of silver (Ag), lithium (Li), and platinum (Pt) compared to HC (all p < 0.001).

CONCLUSION: This multidimensional pilot study integrating microbiota profiling, metal exposure assessment, and cognitive evaluation, revealed elevated fecal excretion of Ag, Li, and Pt in participants with cognitive impairment, suggesting potential interactions between trace metals and neurodegenerative processes. While no significant differences in overall microbial diversity were observed between groups, these findings emphasize the need for larger, longitudinal investigations to elucidate the complex relationships among gut microbiota, metal homeostasis, and cognitive decline.},
}

@article {pmid41525811,
year = {2026},
author = {Pradhan, LK and Das, SK},
title = {Zebrafish neural regeneration: mechanistic insights into human nervous system repair.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.009},
pmid = {41525811},
issn = {1873-7544},
abstract = {The zebrafish (Danio rerio) is a powerful vertebrate model for studying neurodegenerative diseases and regenerative medicine due to its genetic similarity to humans and its unique ability to regenerate the central nervous system (CNS). This review synthesizes key findings on zebrafish neural regeneration across the retina, spinal cord, and brain, emphasizing translational relevance. Zebrafish effectively model disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, stroke, epilepsy, autism spectrum disorders, and CNS injuries. Unlike mammals, they restore damaged axons and recover function through a permissive extracellular matrix, transient inflammation, and glial plasticity. In the retina, Müller glia reprograms after injury to generate progenitors that replace lost neurons, regulated by Wnt/β-catenin, Shh, EGF, Hippo/YAP, and ROCK signaling. In the spinal cord, ependymo-radial glia forms a laminin- and fibronectin-rich "glial bridge," guided by FGF and CTGF signaling, supporting axon regrowth. In the brain, GFAP- and Olig2-positive radial glia drive neurogenesis within ventricular niches, integrating new neurons while maintaining circuit integrity. Regeneration involves transient Notch suppression, context-specific Wnt and FGF activation, and immune modulation without fibrosis. Advances in single-cell RNA sequencing, CRISPR-Cas9, lineage tracing, and multi-omics have identified injury-induced progenitor states, regulators (ascl1a, lin28, sox2, stat3), and epigenetic programs enabling regeneration. Emerging research on bioelectric signaling, microbiota-brain interactions, and lipid mediators further expands systemic understanding. Overall, zebrafish provide a unified model for decoding vertebrate CNS regeneration and guiding therapeutic strategies to restore neural repair in humans.},
}

@article {pmid41525748,
year = {2026},
author = {Lu, W and Gong, Q and Chen, Y and Qiu, S and An, J},
title = {Hippocampus-centered structural covariance network reorganization in Alzheimer's disease: An individualized graph-based biomarker validated by machine learning.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {198},
number = {},
pages = {108542},
doi = {10.1016/j.neunet.2026.108542},
pmid = {41525748},
issn = {1879-2782},
abstract = {Alzheimer's disease (AD) is characterized by progressive brain network disintegration, yet quantifying this process at an individual level remains challenging. This study explores the potential of an individualized differential structural covariance network (IDSCN) as a graph theory-based biomarker to capture disease-specific network reorganization. We found that throughout the AD spectrum, significant progressive atrophy occurred in multiple brain regions, especially the hippocampus. At the same time, the brain underwent a profound structural covariant reorganization, and this reorganization was significantly centered on the hippocampus. Graph theory analysis revealed a significant enhancement in nodal strength and nodal efficiency across widespread brain regions, with the hippocampus, amygdala, middle temporal gyrus, and entorhinal cortex emerging as core hubs of pathological impact. Importantly, betweenness centrality selectively increased only in the bilateral hippocampus, highlighting their critical role as bridges in the pathological propagation network. Machine learning validation confirmed that this individualized network biomarker performs excellently in distinguishing AD patients from cognitively normal individuals, demonstrates comparable efficacy to traditional morphological models in capturing early disease-related changes, and shows potential in differentiating between mild cognitive impairment converters and non-converters. Our study establishes the hippocampus-centered IDSCN as an effective, individualized graph theory-based biomarker, providing new insights into the network pathophysiology of AD and holding significant potential for early diagnosis and prognostic stratification.},
}

@article {pmid41525648,
year = {2026},
author = {Yao, Y and Zhang, H and Tang, X and Li, J and Xu, J and Yang, J and Meng, Y},
title = {Rich-Neighborhood Contrastive Learning Framework for Drug Repositioning via Structural and Semantic Neighbor Fusion.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2026.3651355},
pmid = {41525648},
issn = {2168-2208},
abstract = {Drug repositioning accelerates therapeutic discovery by identifying new indications for approved drugs, substantially reducing the time and cost associated with drug development. However, graph collaborative filtering (GCF)-based methods for predicting drug-disease associations are limited by data sparsity and structural noise, impeding the modeling of latent high-order and semantic relationships. We hypothesize that jointly leveraging complementary information from structural and semantic neighborhoods can alleviate data sparsity and improve predictive performance. To this end, we propose a unified framework, Rich-Neighborhood Contrastive Learning for Drug Repositioning (RCL-DR), which integrates both structural and semantic neighborhood modeling into a LightGCN-based collaborative filtering backbone and optimizes semantic prototypes via an Expectation-Maximization (EM) algorithm. Experiments on three public datasets using 10 × 10- fold cross-validation demonstrate that RCL-DR outperforms representative baselines, achieving an area under the receiver operating characteristic curve (AUROC) of 0.9419 and an area under the precision-recall curve (AUPR) of 0.5126, representing absolute improvements of 0.0345 and 0.0138, respectively. Furthermore, RCL-DR identifies promising drug candidates for Alzheimer's disease (e.g., buspirone) and Parkinson's disease (e.g., trihexyphenidyl) by predicting previously unknown drug-disease associations on the Fdataset and validating them against authoritative databases. In summary, RCL-DR provides a unified contrastive learning framework for robust drug repositioning and precision pharmacology.},
}

@article {pmid41525500,
year = {2025},
author = {Oomens, JE and Harrison, TM and Dage, JL and Russ, KA and Zetterberg, H and Jagust, WJ and Foroud, TM and Biber, S and Mormino, EC and Johnson, SC},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e104199},
doi = {10.1002/alz70856_104199},
pmid = {41525500},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/blood/diagnostic imaging ; *Biomarkers/blood ; Female ; Male ; *tau Proteins/blood ; Aged ; Neuroimaging ; Amyloid beta-Peptides ; Aged, 80 and over ; Brain/diagnostic imaging ; },
abstract = {BACKGROUND: Data accessibility and interoperability across the U.S. Alzheimer's Disease Research Centers (ADRCs) provides necessary resources and data access to enable novel hypothesis testing without additional data collection and will allow end users to rapidly advance our understanding of multiple pathologies or multiple chronic conditions on disease progression within Alzheimer's disease and related diseases. The aim of the current study was to integrate plasma data from the National Centralized Repository for Alzheimer's Disease and Related Dementia's (NCRAD) with ADRC neuroimaging data from the SCAN initiative and National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) demographic data, all publicly available through the NACC Data Platform and Data Front Door. We provide sample descriptives and present the results of initial data explorations.

METHOD: The NACC and NCRAD data request procedures were completed to gain access to the data. We focused on the subset of participants for whom Quanterix Simoa HD-X Alzpath plasma pTau217 data was available (NCRAD). Amyloid pathology was defined based on centiloid values (cut-off >= 20; SCAN initiative). Demographic information was available for all participants (NACC UDS). We integrated data using the NACC identifier and visit age where available. We used Spearman correlations to assess the association between plasma pTau217 and centiloid values and we used ROC analyses to assess amyloid classification performance.

RESULT: Plasma pTau217 data was available for 927 participants (sample descriptives in Table 1). Figure 1 shows the distribution of plasma pTau217 levels across diagnostic groups. In the subset of participants for whom amyloid PET was available (n = 170, Table 1), the Spearman correlation between plasma pTau217 levels and centiloid values was 0.59. Quanterix pTau217 accurately classified amyloid status with a ROC AUC of .92 (95%CI 0.89-0.97; accuracy 85%; Figure 2). Tau PET was available for 135 participants with plasma pTau217 data and 114 participants with both plasma pTau217 and amyloid PET data.

CONCLUSION: Combining the SCAN PET and NCRAD plasma results in a promising resource, already with 36% demographic diversity. Sample sizes will increase through ongoing efforts as part of the SCAN initiative and the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI).},
}

Humans
*Alzheimer Disease/blood/diagnostic imaging
*Biomarkers/blood
Female
Male
*tau Proteins/blood
Aged
Neuroimaging
Amyloid beta-Peptides
Aged, 80 and over
Brain/diagnostic imaging

@article {pmid41525410,
year = {2026},
author = {Custodio, N and Malaga, M and Bustamante-Paytan, D and Huilca-Flores, J and Agüero, K and Verastegui, G and Bartolo, P and Bendezu, D and Yauri, Z and Montesinos, R},
title = {Clinical characterization of probable Dementia with Lewy Bodies based on the initial clinical presentation in a Latin American Low- and Middle- Income Country.},
journal = {Neuro-degenerative diseases},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000550415},
pmid = {41525410},
issn = {1660-2862},
abstract = {BACKGROUND: Dementia with Lewy Bodies (DLB) is a distinct form of dementia characterized by the accumulation of alpha-synuclein in the brain. Early presentations are often heterogeneous, and the impact of this variability on disease progression remains poorly understood. This study explored the initial clinical presentation of DLB among Peruvian patients and its influence on the clinical course.

METHODS: We conducted a retrospective study of patients diagnosed with DLB and Alzheimer's disease (AD) using standard clinical criteria. Cognitive function was assessed using MMSE, INECO Frontal Screening (IFS), and Uniform Data Set (UDS). We classified DLB patients based on their initial symptoms (hallucinations or parkinsonism) and compared their clinical and neuropsychological characteristics. Statistical analyses (ANOVA, chi-squared, Wilcoxon tests, and multivariate linear regression) were used to evaluate group differences and examine how initial symptoms influenced disease progression and cognitive decline.

RESULTS: Forty-six patients with probable DLB between June 2018 and May 2023 were included. The median time from symptom onset to diagnosis was five years. Cognitive symptoms were the most frequent initial presentation, followed by motor and behavioral signs. No significant clinical or neuropsychological differences were found between presentation subgroups at evaluation. Compared to AD patients, those with DLB scored higher on cognitive measures (MMSE, RUDAS) and behavioral symptoms (NPI). Neuropsychological testing revealed DLB patients had more pronounced deficits in visuospatial and executive functions than those with AD.

CONCLUSIONS: In our cohort, patients in the cognitive-onset group reached the threshold for dementia more rapidly. However, the initial presenting symptoms did not result in worse severity across specific cognitive or behavioral domains.},
}

@article {pmid41525398,
year = {2026},
author = {Huan, SY and Otgaar, H and Howe, ML and Liu, YR and Xu, HZ and Wang, J and Yu, J},
title = {A meta-analysis of false memory in healthy and pathological cognitive aging.},
journal = {Psychology and aging},
volume = {},
number = {},
pages = {},
doi = {10.1037/pag0000966},
pmid = {41525398},
issn = {1939-1498},
support = {//National Natural Science Foundation of China/ ; //Fonds Wetenschappelijk Onderzoek/ ; //Ministry of Education in China/ ; },
abstract = {Although there is a consensus about age-related impairments in true memory, the relationship between aging and false memory remains less clear. Both the fuzzy-trace theory and the activation-monitoring theory postulate possible effects of cognitive aging on the processes of encoding, consolidation, and retrieval. Yet, quantitative analyses of cognitive aging, both healthy (younger vs. older adults) and pathological (older adults vs. mild cognitive impairment/Alzheimer's disease), on false memory have not been conducted. We meta-analyzed 150 articles with 414 independent effect sizes and found a robust aging effect of false memory, with older adults showing higher levels of false memory than younger adults in both spontaneous (Hedges's g = 0.538, 95% CI [0.432, 0.644]) and suggestion-induced false memory (Hedges's g = 0.460, 95% CI [0.255, 0.665]). Mild cognitive impairment/Alzheimer's disease patients showed significantly higher levels of spontaneous (Hedges's g = 0.486, 95% CI [0.053, 0.919]) but not suggestion-induced false memory (Hedges's g = 0.608, 95% CI [-0.286, 1.502]) than healthy older adults. For the study and test phase, moderator analyses indicated that experimental material, modality, true memory, paradigm, type of test, and the retention interval significantly influenced aging effect on false memory. For general moderators, participants' age and education level were also significant. Our results underscore the importance of integrating the fuzzy-trace theory and activation-monitoring theory to account for age differences in false memory across types. Both healthy and pathological cognitive aging increase susceptibility to false memory, and the decline in verbatim memory and monitoring functions, combined with hyperactivation during encoding, may account for aging effect in false memory. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41525217,
year = {2026},
author = {Lin, TI and Wang, WL},
title = {Grouped multi-trajectory modeling using finite mixtures of multivariate contaminated normal linear mixed model.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802251404054},
doi = {10.1177/09622802251404054},
pmid = {41525217},
issn = {1477-0334},
abstract = {There has been growing interest across various research domains in the modeling and clustering of multivariate longitudinal trajectories obtained from internally near-homogeneous subgroups. One prominent motivation for such work arises from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort study, which involves multiple clinical measurements, exhibiting complex features such as diverse progression patterns, multimodality, and the presence of atypical observations. To tackle the challenges associated with modeling and clustering such grouped longitudinal data, we propose a finite mixture of multivariate contaminated normal linear mixed model (FM-MCNLMM) and its extended version, referred to as the EFM-MCNLMM, which allows the mixing weights to potentially depend on concomitant covariates. We develop alternating expectation conditional maximization algorithms to carry out maximum likelihood estimation for the two models. The utility and effectiveness of the proposed methodology are demonstrated through simulations and analysis of the ADNI data.},
}