@article {pmid41913218,
year = {2026},
author = {Shao, S and Ribeiro, PH and Orlenko, A and Cardone, KM and Ramirez, CM and Shen, L and Ritchie, MD and Moore, JH},
title = {A biology-based quality-diversity algorithm for drug repurposing in Alzheimer's disease using automated machine learning.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00550-4},
pmid = {41913218},
issn = {1756-0381},
}

@article {pmid41913245,
year = {2026},
author = {Kim, SJ and Kim, MJ and Kim, JS and Jang, J and Choi, W and Lee, HJ and Song, JH and Hoe, HS},
title = {AI-enabled digital phenotyping for Alzheimer's disease: a review of multimodal sensor integration and symptom trajectories.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02013-8},
pmid = {41913245},
issn = {1758-9193},
support = {RS-2024-00357857//NRF/ ; RS-2024-00343370//KDRC/ ; H0501-25-1001//NIPA/ ; 26-BR-02-04, 26-BR-05-01, and 26-BR-06-01//KBRI/ ; },
}

@article {pmid41913259,
year = {2026},
author = {Opwonya, J and Ku, B and van der Heide, F and Lee, KH and Kim, JI and Kim, JU},
title = {Linking eye movements, pupil responses, and brain networks in early cognitive decline.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02035-2},
pmid = {41913259},
issn = {1758-9193},
support = {KSN2313022//Korean Government/ ; KSN2313022//Korean Government/ ; },
}

@article {pmid41913274,
year = {2026},
author = {Delgado, A and Davidson, K and Parker, D and Bryant, J and Winstead, V and Yildiz, M and Pickering, CEZ and Pickering, AM},
title = {Weekly fluctuations of plasma amyloid-beta in Alzheimer's disease: implications for biomarker reliability.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02040-5},
pmid = {41913274},
issn = {1758-9193},
support = {Aging R01 RMH121928C/MH/NIMH NIH HHS/United States ; Aging R01 RMH121928C/MH/NIMH NIH HHS/United States ; R01 AG06531/AG/NIA NIH HHS/United States ; },
}

@article {pmid41913828,
year = {2026},
author = {Frolov, A and Maglasang, M and Guzman, M and Echols, MS and Daly, DT},
title = {Coexistence of Rheumatoid Arthritis, Cerebrovascular Disease, and Alzheimer's Disease: A Case Study With Genetic Insights.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104395},
pmid = {41913828},
issn = {2168-8184},
abstract = {To gain new insights into the molecular underpinnings of coexisting rheumatoid arthritis (RA), cerebrovascular disease (cVD), and Alzheimer's disease (AD), we performed postmortem neuropathological examination and genetic screening of two individuals. The first individual (donor 1, D1) was a 74-year-old man who was diagnosed with both RA and AD and who also underwent hip replacement surgery bilaterally. The second individual (donor 2, D2) was a 90-year-old man with a reported diagnosis of RA, as well as two left hip replacements. A thorough histochemical (hematoxylin and eosin, H&E) and immunohistochemical (β-amyloid and tau protein) examination of D1 and D2 brains revealed the presence of AD-related pathology in both individuals, with AD stages being mild in D1 and intermediate in D2. The cVD-related pathology was also evident in both cases and was characterized by several microbleeds indicative of a compromised blood-brain barrier (BBB) integrity. Blood vessel wall thickening, a characteristic of arteriosclerosis, was significant in D1 but minor in D2. Therefore, the earlier RA diagnoses, along with the results of the neuropathological examination, indicated the coexistence in the donors of three major diseases: RA, cVD, and AD. The whole exome sequencing (WES) of DNA procured from D1 and D2 performed on the next-generation sequencing (NGS) Illumina platform (San Diego, CA) was followed by a very stringent bioinformatics analysis that yielded multiple genes with rare (minor allele frequency {MAF}
≤ 0.01) genetic pathological/deleterious variants associated with RA, cVD, and AD. Seven of those genes, AQP7, ARSD, FAM160A1, HYDIN, IGSF3, OTOP1, and PRSS1, were shared between D1 and D2, with all but FAM160A1 having identical variants in both donors. Intriguingly, the subsequent analysis of the respective literature indicated that FAM160A1, IGSF3, and PRSS1 were pleiotropic as they could be linked to all three coexisting diseases: RA, cVD, and AD. Altogether, the data presented herein are consistent with the notion that AD, cVD, and RA, when they coexist in humans, could be underpinned by a combination of polygenic and pleiotropic factors. Yet, a significant number of affected genes in the donors associated with bone and cartilage physiology point toward the possibility of joints being also damaged directly and independently of RA.},
}

@article {pmid41913857,
year = {2026},
author = {Chen, W and Ngo, MT and Tewary, S},
title = {Evaluating Knowledge Outcomes of the Age-Friendly Health Systems and 4Ms Module in Medical Education: A Comparative Study of YouTube vs. Virtual Reality Platforms.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104394},
pmid = {41913857},
issn = {2168-8184},
abstract = {This study evaluated and compared the effectiveness of Virtual Reality (VR) versus YouTube-based training in teaching the 4Ms framework: What Matters, Medication, Mentation, and Mobility, within a geriatric medicine course for second-year medical students. Pre- and post-training surveys were administered via REDCap, and matched sample t-tests and Cohen's d effect size were conducted. VR training resulted in a mean knowledge increase of 0.55 (2.49 to 3.04, N=90), while YouTube training showed a 0.53 increase (2.58 to 3.11, N=76). Both showed statistically significant gains (p <0.001), with YouTube having a larger t-value (-7.39 vs. -6.41), but VR demonstrating a greater effect size (Cohen's d = 0.82 vs. 0.62). However, an independent samples t-test revealed no significance in knowledge gains between groups (p = 0.80). These findings suggest that both modalities effectively enhance knowledge, with VR demonstrating a stronger effect size, likely due to its interactive effect. This highlights its potential use in medical education on geriatrics.},
}

@article {pmid41914164,
year = {2026},
author = {Sukumaran, ES and Ganamurali, N and Pm, A and Raja, A and Narasimha, MK and Sabarathinam, S},
title = {Fructose Metabolism and Disease Mechanisms: From Nutritional Excess to Obesity and Multiorgan Pathophysiology.},
journal = {Frontiers in bioscience (Elite edition)},
volume = {18},
number = {1},
pages = {46304},
doi = {10.31083/FBE46304},
pmid = {41914164},
issn = {1945-0508},
mesh = {Humans ; *Fructose/metabolism/adverse effects ; *Obesity/metabolism/physiopathology/etiology ; Animals ; },
abstract = {Excessive fructose consumption has emerged as a critical driver of obesity and metabolic dysfunction, with far-reaching implications for multiple organ systems. This review synthesizes current evidence on the biochemical and molecular pathways underlying fructose induced disease mechanisms, discussing how fructose metabolism activates the "survival switch", promotes fat storage, and generates uric acid, mitochondrial dysfunction, and oxidative stress, thereby disrupting energy homeostasis. Key organ-specific consequences are explored, including hepatic steatosis and progression to non-alcoholic fatty liver disease, pancreatic β-cell dysfunction, renal fibrosis, intestinal barrier disruption with microbial dysbiosis, cardiometabolic impairment, pulmonary inflammation, and neurocognitive decline with relevance to Alzheimer's disease. Moreover, mechanistic insights highlight the role of fructokinase C activation, adenosine triphosphate (ATP) depletion, leptin resistance, pro-inflammatory signaling (mechanistic target of rapamycin complex-1 (mTORC1), renin angiotensin system (RAS), Toll-like receptor 4 (TLR4)), and cross-talk between fructose metabolism and organ-specific pathophysiology. Animal and human studies consistently reinforce the central role of fructose overload in driving obesity and associated complications. Meanwhile, this review frames fructose not merely as a caloric contributor but as a metabolic disruptor, thereby underscoring the urgent need for public health interventions, dietary regulation, and mechanistic research to mitigate fructose-driven metabolic disease.},
}

Humans
*Fructose/metabolism/adverse effects
*Obesity/metabolism/physiopathology/etiology
Animals

@article {pmid41914285,
year = {2026},
author = {Stefano, GB},
title = {NAD[+] Homeostasis and Mitochondrial Modifiability: Resilience in Alzheimer's Disease.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {49714},
doi = {10.31083/FBL49714},
pmid = {41914285},
issn = {2768-6698},
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *NAD/metabolism ; *Mitochondria/metabolism ; *Homeostasis ; Animals ; Oxidation-Reduction ; Energy Metabolism ; },
abstract = {Alzheimer's disease (AD) is increasingly associated with mitochondrial dysfunction and disrupted metabolism. Thus, the maintenance of nicotinamide adenine dinucleotide (NAD[+]) homeostasis is proposed as a potential therapeutic strategy. Toward this end, we suggest that AD-related mitochondrial dysfunction might be viewed as a regulatable, redox-dependent vulnerability rather than an inherently degenerative and irreversible process. This perspective advances an evolutionary model in which NAD[+]-mediated redox systems represent a conserved regulatory axis, and that destabilization of this axis during aging may increase susceptibility to degeneration. Here, we assess the potential of a therapeutic approach that combines this understanding of mitochondrial energy metabolism with results from preclinical studies demonstrating the impact of pharmacologic correction of NAD[+] homeostasis (e.g., P7C3-A20) as contextual motivation. We explicitly elevate redox balance, rather than absolute NAD[+] abundance, as the mechanistically dominant variable that shapes mitochondrial resilience, inflammatory tone, and neurovascular stability. Accordingly, the key unresolved issue is whether specific physiologic benefits might accrue from increased NAD[+] availability per se or rather, the restoration of the NAD[+]/NADH redox ratio, with important implications for the interpretation of the results of directed metabolic interventions. Within this framework, metabolic failure in AD can be understood as an upstream permissive condition that explains, rather than replaces, canonical amyloid-β and tau-associated pathologies. While extended human lifespan may expose late-life vulnerabilities in otherwise conserved metabolic systems, claims of causal primacy, disease reversibility, and cross-neurodegenerative generalization remain premature, underscoring the need for redox-resolved, genetic, and clinical validation.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*NAD/metabolism
*Mitochondria/metabolism
*Homeostasis
Animals
Oxidation-Reduction
Energy Metabolism

@article {pmid41914304,
year = {2026},
author = {Wei, H and Wang, B and Yang, J and Liao, L},
title = {The Mechanism of PANoptosis in Alzheimer's Disease: Exploring the Multiple Network Regulation of Cell Death.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {45499},
doi = {10.31083/FBL45499},
pmid = {41914304},
issn = {2768-6698},
support = {S20250012//Sichuan Medical Association Medical Scientific Research Project/ ; },
mesh = {*Alzheimer Disease/pathology/metabolism ; Humans ; Amyloid beta-Peptides/metabolism ; Cell Death ; tau Proteins/metabolism ; Animals ; Neurons/pathology/metabolism ; Plaque, Amyloid/pathology/metabolism ; Brain/pathology/metabolism ; *Necroptosis ; Apoptosis ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting the geriatric population, characterized by progressive cognitive impairment and behavioral abnormalities. Due to the absence of effective disease-modifying therapies, AD imposes a substantial burden on patients and their families. The etiology and pathogenesis of AD have not been fully elucidated; multiple pathological alterations have been implicated, including the deposition of β-amyloid (Aβ) plaques, abnormal tau phosphorylation, and neuroinflammatory responses. These pathological changes contribute to neuronal damage, synaptic dysfunction, and neuronal death, ultimately leading to brain atrophy. Recent studies have identified PANoptosis as a critical regulatory mechanism of programmed cell death that influences the pathological progression of AD through multiple pathways, including modulation of Aβ plaque deposition and regulating neuroinflammatory responses. However, the precise mechanisms of these effects remain unclear. This review aims to comprehensively analyze recent research findings, focusing on the regulatory role of PANoptosis in AD, exploring the specific manifestations of the intricate network of cell death regulation in AD pathogenesis. By providing a systematic overview of emerging findings, this review offers new insights into the pathogenesis of AD and highlights potential directions for the development of targeted therapeutic strategies.},
}

*Alzheimer Disease/pathology/metabolism
Humans
Amyloid beta-Peptides/metabolism
Cell Death
tau Proteins/metabolism
Animals
Neurons/pathology/metabolism
Plaque, Amyloid/pathology/metabolism
Brain/pathology/metabolism
*Necroptosis
Apoptosis

@article {pmid41914305,
year = {2026},
author = {Xie, JL and Hu, XH and Wu, CL and Jin, Q and Pan, JP},
title = {DHA Ameliorates Alzheimer's Disease by Attenuating Microglial Pyroptosis via Regulation of the HOXA9-NLRP3 Pathway.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {3},
pages = {46572},
doi = {10.31083/FBL46572},
pmid = {41914305},
issn = {2768-6698},
support = {20232BAB206049//Jiangxi Provincial Natural Science Foundation General Project/ ; },
mesh = {*Alzheimer Disease/drug therapy/metabolism ; *Docosahexaenoic Acids/pharmacology/therapeutic use ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Pyroptosis/drug effects ; Mice ; Humans ; *Homeodomain Proteins/metabolism/genetics ; *Microglia/drug effects/metabolism ; Amyloid beta-Peptides ; Signal Transduction/drug effects ; Male ; Mice, Transgenic ; Disease Models, Animal ; Peptide Fragments ; Neuroprotective Agents/pharmacology ; Mice, Inbred C57BL ; Cell Line ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) involves a progressive deterioration of cognitive abilities, memory loss, and persistent brain inflammation. Emerging evidence indicates that pyroptosis mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, contributes significantly to AD development. Docosahexaenoic acid (DHA) has demonstrated neuroprotective properties; however, the precise mechanisms by which it modulates pyroptosis in AD have yet to remained incompletely elucidated.

OBJECTIVE: To explore the role of DHA in modulating microglial pyroptosis via the HOXA9-NLRP3 pathway in an AD model.

METHODS: Effects of DHA on Aβ25-35-induced pyroptosis were assessed in human microglial clone 3 (HMC3) human microglial cells using CCK-8, western blotting, immunofluorescence, and Enzyme-linked Immunosorbent Assay (ELISA) assays. The role of homeobox A9 (HOXA9) in pyroptosis regulation was evaluated through overexpression and knockdown experiments. Dual-luciferase reporter assays together with chromatin immunoprecipitation (ChIP) were used to verify the interaction of HOXA9 to NLRP3 promoter. Amyloid precursor protein / Presenilin-1 double-transgenic (APP/PS1) transgenic AD mice underwent DHA treatment in vivo, and cognitive performance was assessed using the Morris water maze paradigm. Expression of HOXA9, NLRP3, and pyroptosis-related proteins were analyzed by Quantitative Real-time Reverse Transcription PCR (qRT-PCR), Western blotting, and immunofluorescence.

RESULTS: DHA treatment significantly reduced Aβ25-35-induced microglial pyroptosis, as indicated by decreased levels of p30-Gasdermin D (GSDMD), cleaved-caspase-1, IL-1β, and IL-18. HOXA9 overexpression reversed the protective effects of DHA, whereas NLRP3 inhibition by MCC950 enhanced DHA inhibition of pyroptosis. Dual-luciferase and ChIP assays confirmed that HOXA9 directly regulates NLRP3 transcription. In APP/PS1 mice, DHA administration enhanced cognitive performance while simultaneously decreasing the expression of pyroptosis-related markers and inflammatory mediators in brain. Inhibition of NLRP3 signaling by MCC950 further strengthened the neuroprotective actions of DHA.

CONCLUSION: DHA ameliorates AD-related cognitive decline and reduces microglial pyroptosis through suppressing the HOXA9-NLRP3 axis. These results offer novel insights into the molecular basis of DHA-mediated neuroprotection and highlight potential therapeutic targets for AD.},
}

*Alzheimer Disease/drug therapy/metabolism
*Docosahexaenoic Acids/pharmacology/therapeutic use
Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
*Pyroptosis/drug effects
Mice
Humans
*Homeodomain Proteins/metabolism/genetics
*Microglia/drug effects/metabolism
Amyloid beta-Peptides
Signal Transduction/drug effects
Male
Mice, Transgenic
Disease Models, Animal
Peptide Fragments
Neuroprotective Agents/pharmacology
Mice, Inbred C57BL
Cell Line

@article {pmid41914380,
year = {2026},
author = {Chen, L and Chen, EW and Chen, BW and Wang, D},
title = {Retinol Taking a Detour Promotes Neural Stem Cell Self-Renewal In Vivo Accompanied by Down-Regulation of Some Retinoic Acid Receptors.},
journal = {Stem cells and development},
volume = {},
number = {},
pages = {15473287261436286},
doi = {10.1177/15473287261436286},
pmid = {41914380},
issn = {1557-8534},
abstract = {Since our previous studies have indicated retinol promotes self-renewal of embryonic stem cells in vitro culture, we speculate that retinol may be directly involved in regulating adult stem cell self-renewal or developmental function in vivo. Vitamin A or retinoic acid (RA) solution was first injected into the abdominal cavities of mice, and then self-renewal and development marker gene expressions were investigated. The in vivo effects of retinol and RA on RA receptor expressions were further examined. The results showed that retinol not only significantly promotes self-renewal of neural stem cells in vivo but also induces orientational development of neural stem cells in vivo and significantly downregulates the expression of some RA receptor gene expression in the brain. This study provides experimental and theoretical bases for elucidating the regulation mechanism of retinol-mediated cell development in vivo, especially in brain, and the development of therapeutic drugs for neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Multiple sclerosis, and Huntington's disease.},
}

@article {pmid41914594,
year = {2026},
author = {Rebolo, M and Maroco, J and Melo, G and Mendonça, A},
title = {Coping Strategies Used by Caregivers of Patients With Mild Cognitive Impairment due to Alzheimer's Disease - A Longitudinal Study.},
journal = {Journal of geriatric psychiatry and neurology},
volume = {},
number = {},
pages = {8919887261439756},
doi = {10.1177/08919887261439756},
pmid = {41914594},
issn = {1552-5708},
abstract = {BackgroundAdvances in biomarker research allow precise diagnosis of Alzheimer's disease (AD) in patients with Mild Cognitive Impairment (MCI). Communicating this diagnosis may reduce uncertainty and aid care planning but can also increase anxiety, distress, or anticipatory burden among care partners.ObjectiveTo characterise coping strategies used by caregivers of patients recently diagnosed with MCI due to AD and examine their evolution.MethodsThirty caregivers of patients with MCI due to AD were recruited from a memory clinic, assessed at baseline, and followed over 18 months. Caregiver personality, burden, depressive and anxiety symptoms, perceived relationship closeness, and distress related to patient neuropsychiatric symptoms were also assessed at baseline. Coping was assessed longitudinally using the Brief COPE, grouping its 14 subscales into problem-focused, emotion-focused, and dysfunctional coping.ResultsCaregivers used problem-focused (3.37 ± 1.02) and emotion-focused (2.91 ± 0.86) more often than dysfunctional coping (1.13 ± 0.56). Dysfunctional coping was associated with lower perceived relationship closeness, higher burden, and greater distress related to neuropsychiatric symptoms, while emotion-focused coping was inversely associated with anxiety and depression. Trends suggested associations between emotion-focused coping and extraversion, and between problem-focused coping and conscientiousness. Coping patterns remained stable over time. Caregivers reported elevated psychological distress.ConclusionCaregivers of patients with MCI due to AD experience considerable psychological distress but appear to rely primarily on adaptive coping strategies. The stability of coping patterns suggests that coping responses may begin to consolidate early in the caregiving trajectory. Given the exploratory nature of our study, further longitudinal research is needed.},
}

@article {pmid41914617,
year = {2026},
author = {Diniz, BS},
title = {Do people with bipolar disorder have a greater risk of dementia in later life?.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/14737175.2026.2652297},
pmid = {41914617},
issn = {1744-8360},
}

@article {pmid41914643,
year = {2026},
author = {Doan, VU and Xu, Y and Wang, Z and Kaminski, AM and Pedersen, LC and Liu, J},
title = {Development of a Specific and Sensitive LC-MS/MS Method to Quantify Heparan Sulfate 3-O-Sulfotransferase-1 Activity.},
journal = {Glycobiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/glycob/cwag024},
pmid = {41914643},
issn = {1460-2423},
abstract = {Heparan sulfate (HS) is a highly sulfated glycan that regulates diverse biological processes through specific sulfation patterns. Among these, 3-O-sulfation catalyzed by heparan sulfate 3-O-sulfotransferase-1 (3OST-1) is rare but functionally critical, influencing anticoagulation and contributing to the progression of Alzheimer's disease and cancer progression. However, direct measurement of 3OST-1 activity in biological systems has been limited by the lack of sensitive and specific assays. Here we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using a structurally defined HS hexasaccharide substrate and 13C-labeled internal standards. This method enables nanogram-level detection of 3-O-sulfated products following heparinase digestion and AMAC derivatization. The LC-MS/MS assay demonstrated 100-fold improved sensitivity compared to HPLC and successfully quantified endogenous 3OST-1 activity in HCT-116 cells and conditioned media. Using this assay, we confirmed that the 3OST-1 E86Q mutant acts as a dominant-negative inhibitor. E86Q mutant retains substrate and donor binding but abolishes catalytic activity, reducing wild-type 3OST-1-like activity by >80% in vitro and significantly decreasing 3-O-sulfated HS products in cells without affecting overall HS abundance. This assay provides the first quantitative tool for 3OST-1-like activity and establishes a dominant-negative strategy for functional studies, offering new opportunities for biomarker development and therapeutic targeting in HS-related pathologies.},
}

@article {pmid41914924,
year = {2026},
author = {Stagge, F and Saylor, AK and Dallas, ON and Johnson, AL and Palmer, KM and Fromm, D and Lanzi, AM},
title = {Increasing Educator Resources for Mild Cognitive Impairment and Dementia Using a Knowledge-to-Action Framework: The Development of DementiaBank Grand Rounds.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-21},
doi = {10.1044/2026_AJSLP-25-00396},
pmid = {41914924},
issn = {1558-9110},
abstract = {PURPOSE: An educational gap exists in content knowledge and clinical education for speech-language pathologists concerning the treatment and assessment of cognitive-communication disorders from mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). This gap may result in less effective speech-language pathology services for this population. The overarching goal of this project was to enhance graduate speech-language pathology education about MCI and dementia due to AD to improve the quality of future service providers.

METHOD: To achieve this goal, this project had two objectives: first, to conduct a survey to understand speech-language pathology graduate school education practices in clinical and classroom settings regarding cognitive-communication disorders from MCI or dementia due to AD and, second, to conduct focus groups to guide the development of an online educational resource, informed by speech-language pathology graduate school educators. A knowledge-to-action (KTA) conceptual framework provided guidance to translate findings from the survey and focus groups into a highly implementable educational resource.

RESULTS: Educators of graduate speech-language pathology students reported a crucial need for additional accessible resources to assist them in teaching or supervising cognitive-communication disorders from MCI or dementia due to AD. The existing TalkBank educational resource, Grand Rounds, was explored through educator focus groups, and feedback directly informed the creation of a new educational resource tailored for this population.

CONCLUSIONS: Overall, an educational resource, DementiaBank Grand Rounds, was successfully developed for cognitive-communication disorders associated with MCI and dementia due to AD, utilizing the KTA framework. DementiaBank Grand Rounds may serve as a resource to support learners and educators and address the current gap in content knowledge and clinical education.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.31839664.},
}

@article {pmid41915038,
year = {2026},
author = {Xia, Y and Johnson, K and Fakhri, GE and Guehl, NJ and van de Giessen, E and Coomans, EC and Pijnenburg, YAL and Ossenkoppele, R and Groot, C},
title = {Bayesian modelling demonstrates clinically relevant heterogeneity in Tau PET patterns in Alzheimer's disease.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41915038},
issn = {1619-7089},
support = {10510022110010/ZONMW_/ZonMw/Netherlands ; WE.03-2024-06//Alzheimer Nederland/ ; 949570//H2020 European Research Council/ ; },
}

@article {pmid41915112,
year = {2026},
author = {Zhou, Y and Li, S and Xiang, J},
title = {The role of MicroRNAs in Alzheimer's disease: from pathogenesis to therapeutic potential.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {41915112},
issn = {1573-4978},
mesh = {*Alzheimer Disease/genetics/therapy/metabolism/pathology ; Humans ; *MicroRNAs/genetics/metabolism ; Biomarkers/metabolism ; tau Proteins/metabolism/genetics ; Amyloid beta-Peptides/metabolism/genetics ; Animals ; },
abstract = {Alzheimer's disease (AD) is a major neurodegenerative disorder that severely impacts the global elderly population. It is characterized by progressive memory loss, cognitive impairment, and neuropsychiatric disturbances. To date, AD lacks definitive curative treatments, making it a persistent clinical challenge. Consequently, there is an urgent need to develop cost-effective and highly specific biomarkers for the early detection of AD. MicroRNAs (miRNAs) are evolutionarily conserved, small non-coding RNAs. They are highly enriched in the central nervous system (CNS), where they orchestrate essential processes like axonal outgrowth, dendritic arborization, and synaptic plasticity. In AD patients, miRNAs actively regulate disease progression and exhibit abnormal expression profiles in peripheral blood. By modulating target genes across key pathological pathways-including β-amyloid (Aβ) aggregation, tau hyperphosphorylation, and neuroinflammation-miRNAs act as pivotal regulators of AD initiation. Therefore, systematically investigating their diagnostic and therapeutic potential could drive the development of innovative AD management strategies.},
}

*Alzheimer Disease/genetics/therapy/metabolism/pathology
Humans
*MicroRNAs/genetics/metabolism
Biomarkers/metabolism
tau Proteins/metabolism/genetics
Amyloid beta-Peptides/metabolism/genetics
Animals

@article {pmid41915182,
year = {2026},
author = {Xu, J and Chen, L and Chen, Z and Song, Y and Fu, Z and Ao, X and Sun, X and Chen, Y and Wei, W and Sun, C and Tian, Z},
title = {Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study.},
journal = {European journal of nutrition},
volume = {65},
number = {3},
pages = {},
pmid = {41915182},
issn = {1436-6215},
support = {U21A20398//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Female ; Male ; United Kingdom/epidemiology ; *Dementia/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; *Obesity, Abdominal/complications/epidemiology ; Middle Aged ; *Dietary Fats/administration & dosage/adverse effects ; Aged ; Risk Factors ; Cohort Studies ; Sex Factors ; Biological Specimen Banks ; Alzheimer Disease/epidemiology ; Prospective Studies ; Incidence ; Diet ; UK Biobank ; },
abstract = {PURPOSE: To clarify the unclear association of dietary fat intake with dementia and cognitive impairment in individuals with central obesity, this study explored links of proportion of energy from dietary fat (PEFDF) to dementia risk and cognitive decline.

METHODS: A total of 128,160 participants from the UK Biobank were included in this study. Cox regression, logistics regression and univariate linear regression models were used to analyze the associations between PEFDF and the risk of dementia and cognitive impairment.

RESULTS: Among women, PEFDF showed a potential nonlinear association with all-cause dementia and Alzheimer's disease incidence, whereas no significant association was observed in men. Notably, obese women with a moderately high percentage of energy from fat (MHF) had the lowest risk of all-cause dementia (HR, 0.746; 95% CI, 0.590-0.943) and Alzheimer's disease incidence (HR, 0.606; 95% CI, 0.419-0.876). Furthermore, MHF was associated with higher fluid intelligence test (FIT) scores (β, 0.213; 95% CI, 0.185-0.241), numerical memory test (NMT) scores (β, 0.091; 95% CI, 0.062-0.119), and prospective memory test (PMT) scores (OR, 1.187; 95% CI, 1.145-1.231) in women; and MHF was significantly associated with higher FIT (β, 0.198; 95% CI, 0.169-0.228) scores and PMT scores (OR, 1.114; 95% CI, 1.073-1.156) in man.

CONCLUSIONS: Our findings showed that MHF is positively associated with neurocognitive function in central obesity, especially in women. These results underscore the potential of scientifically effective dietary intervention in mitigating risk of dementias such as Alzheimer's disease.},
}

Humans
Female
Male
United Kingdom/epidemiology
*Dementia/epidemiology/etiology
*Cognitive Dysfunction/epidemiology/etiology
*Obesity, Abdominal/complications/epidemiology
Middle Aged
*Dietary Fats/administration & dosage/adverse effects
Aged
Risk Factors
Cohort Studies
Sex Factors
Biological Specimen Banks
Alzheimer Disease/epidemiology
Prospective Studies
Incidence
Diet
UK Biobank

@article {pmid41915254,
year = {2026},
author = {Fahim, F and Farajzadeh, M and Rahatijafarabad, B and Mohammadi, AM and Khorram, A and Mostafaei, M and Nikbakht, O and Zamiri, R and Sepehrian, N and Oveisi, S and Zali, A},
title = {Deep brain stimulation of the fornix for Alzheimer's disease: A systematic review and meta-analysis of cognitive outcomes.},
journal = {Neurosurgical review},
volume = {49},
number = {1},
pages = {},
pmid = {41915254},
issn = {1437-2320},
}

@article {pmid41915294,
year = {2026},
author = {Farzeen, I and Batool, M and Saeed, S and Mustafa, G and Yasmeen, M and Nazir, MM and Ashraf, A},
title = {Metabolic reprogramming of neurons in alzheimer disease: a biochemical perspective.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41915294},
issn = {1573-7365},
}

@article {pmid41915305,
year = {2026},
author = {Fukuchi, M and Izumi, H and Sakurai, D and Shinohara, Y and Arimura, K and Saito-Moriya, R and Kitada, N and Huanood, G and Nakasone, H and Maki, SA and Mori, H},
title = {Visualizing Changes in Brain-Derived Neurotrophic Factor Expression in Living Mice Using the All-Engineered Bioluminescence Imaging System AkaBLI.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915305},
issn = {1559-1182},
support = {22K11859//Japan Society for the Promotion of Science/ ; },
mesh = {Animals ; *Brain-Derived Neurotrophic Factor/metabolism/genetics ; Mice, Transgenic ; *Luminescent Measurements/methods ; Brain/metabolism ; Mice ; Alzheimer Disease/metabolism ; Disease Models, Animal ; },
abstract = {Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal development, synaptic plasticity, and cognitive function, and its dysregulation is implicated in various neurodegenerative and neuropsychiatric disorders. To noninvasively monitor dynamic changes in Bdnf expression in vivo, we developed a novel transgenic mouse line, Bdnf-AkaLuc transgenic (Tg) mice, in which the coding region of BDNF was replaced in a BAC transgene with a mutant luciferase, AkaLuc. This luciferase is optimized for the synthetic substrate AkaLumine, which emits near-infrared bioluminescence suitable for deep-tissue imaging. This engineered bioluminescence imaging (BLI) system, termed AkaBLI, enables robust and highly sensitive detection of bioluminescence in the brains of living mice, significantly outperforming our previous Bdnf-Luciferase Tg model. Using this system, we successfully visualized activity-dependent Bdnf mRNA induction in response to pilocarpine-induced status epilepticus. To overcome the limitations of repeated imaging, we identified optimal BLI intervals and established a hairless Bdnf-AkaLuc Tg line, facilitating long-term longitudinal monitoring. Furthermore, by crossing Bdnf-AkaLuc Tg mice with 5xFAD Alzheimer's disease model mice, we successfully visualized reductions in Bdnf expression in the brains of living 5xFAD mice. Our study introduces a powerful tool for noninvasive, continuous visualization of Bdnf regulation under both physiological and disease-related conditions. This imaging approach holds potential for advancing our understanding of BDNF-related brain function and for evaluating therapeutic strategies targeting BDNF in neurological disorders.},
}

Animals
*Brain-Derived Neurotrophic Factor/metabolism/genetics
Mice, Transgenic
*Luminescent Measurements/methods
Brain/metabolism
Mice
Alzheimer Disease/metabolism
Disease Models, Animal

@article {pmid41915331,
year = {2026},
author = {Yang, L and Song, G and Parker, E and Yang, L},
title = {Inhaled General Anesthetics in Alzheimer's Disease Progression: Divergent Effects, Underlying Mechanisms, and Future Perspectives.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915331},
issn = {1559-1182},
support = {32300959//National Natural Science Foundation of China/ ; SL2024A04J00578//Guangzhou Scientific Research Grant/ ; 22KJ04//SCNU Young Faculty Development Program/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/drug therapy/metabolism ; *Disease Progression ; Animals ; *Anesthetics, Inhalation/therapeutic use/adverse effects/pharmacology ; *Anesthetics, General/therapeutic use ; Neuroprotective Agents/therapeutic use ; },
abstract = {Alzheimer's disease (AD) is a devastating, age-related neurodegenerative disorder characterized by progressive cognitive decline, neuronal loss, and hallmark pathologies like β-amyloid (Aβ) deposition and tau hyperphosphorylation. With global aging, more AD patients or high-risk individuals undergo perioperative care, exposing them to inhaled anesthetics such as isoflurane and sevoflurane. Preclinical and clinical evidence on these agents' effects on AD pathogenesis remains conflicting, ranging from exacerbating pathology to neuroprotection, highlighting the critical need to clarify the context-dependent effects and mechanisms driving these outcomes. This review synthesizes how inhaled anesthetics interact with core AD pathologies, highlighting the widely used inhaled anesthetics on AD progression, molecular targets, and exposure parameters. Furthermore, we discuss emerging neuroprotective interventions (e.g., antioxidants, trehalose) that mitigate neuronal damage. These findings inform personalized perioperative strategies for AD-susceptible populations, aiming to reduce iatrogenic risks and improve long-term neurological outcomes.},
}

Humans
*Alzheimer Disease/pathology/drug therapy/metabolism
*Disease Progression
Animals
*Anesthetics, Inhalation/therapeutic use/adverse effects/pharmacology
*Anesthetics, General/therapeutic use
Neuroprotective Agents/therapeutic use

@article {pmid41915334,
year = {2026},
author = {Zhang, L and Jia, H and Pan, C and Xu, Z and Liu, S},
title = {The Multifaceted Roles of GPR120 in Central Nervous System Disorders: Mechanistic Insights and Therapeutic Implications.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41915334},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Central Nervous System Diseases/metabolism/therapy/drug therapy ; Signal Transduction ; },
abstract = {G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), is a receptor for ω-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). It is widely expressed in the central nervous system on microglia, astrocytes, and neurons, where it regulates neuroinflammation and homeostasis. This review summarizes the mechanism insights and therapeutic potential of GPR120 in neurological and psychiatric disorders. Mechanistic studies indicated that GPR120 activation predominantly engages a β-arrestin2-dependent signaling pathway, which inhibits the TAK1/TAB1 complex, suppresses NF-κB and NLRP3 inflammasome pathways, and thus alleviates neuroinflammation. GPR120 signaling also regulates mitophagy and mitigates endoplasmic reticulum stress, promoting neuronal survival and function. In disease models, GPR120 activation is consistently neuroprotective, reducing seizure severity in epilepsy by inhibiting the NLRP3/caspase-1/IL-1β axis, decreasing pathological deposits in Alzheimer's disease by enhancing Aβ clearance, improving post-ischemic outcomes in stroke via anti-apoptotic and anti-inflammatory mechanisms, and improving behavior in depression models by suppressing microglial M1 polarization and restoring synaptic plasticity. Preclinical studies support the efficacy of selective GPR120 agonists (such as TUG-891, CpdA). However, clinical translation faces major challenges: differences in receptor pharmacology between humans and mice (about 82% sequence homology), weak endogenous ligands, high plasma protein binding (> 99%), and the absence of neurologically focused clinical trials. Future research should focus on addressing species differences, optimizing brain-targeted delivery strategies, and advancing translational studies from preclinical to clinical settings to evaluate the practical application value of GPR120 in central nervous system disorders.},
}

Humans
Animals
*Receptors, G-Protein-Coupled/metabolism
*Central Nervous System Diseases/metabolism/therapy/drug therapy
Signal Transduction

@article {pmid41915395,
year = {2026},
author = {Macedo, AC and de Lima, AG and Miaw, ISL and Bizzi, IH and Balbino, JMV and Therriault, J and Zimmer, ER and Ghezzi, P and Rosa-Neto, P},
title = {Quality Gaps in Online Media Coverage of Antiamyloid Monoclonal Antibodies for Alzheimer Disease.},
journal = {JAMA network open},
volume = {9},
number = {3},
pages = {e265026},
doi = {10.1001/jamanetworkopen.2026.5026},
pmid = {41915395},
issn = {2574-3805},
}

@article {pmid41915524,
year = {2026},
author = {Feng, R and Chen, H and Yao, Y and Wu, L and Liang, T and Xiang, W and Li, J and Loo, CK and Yu, J and Wang, W and Li, J},
title = {Towards Cognitive Impairment Screening in Elderly Communities with Audio-Visual Modal Disentangled Representation Learning.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2026.3679693},
pmid = {41915524},
issn = {2168-2208},
abstract = {Alzheimer's disease (AD) is pressing global health concerns, for which early diagnosis is critical to effective intervention. However, conventional approaches, including neuropsychological assessments and neuroimaging techniques, are resource-intensive and impractical for community-level screening. In contrast, artificial intelligence-driven behavioral analyses, including speech pattern and facial expression recognition, have demonstrated considerable potential for scalable and non invasive cognitive assessment. This work presents a community-oriented intelligent screening system for cognitive impairment screening in elderly populations. As a foundation, we introduce CIR-AV, the first large-scale Mandarin-based multimodal dataset for cognitive impairment recognition in Chinese older adults, encompassing 574 community-dwelling participants with comprehensive facial expression and speech data. Building upon this resource, we propose DiVA, a disentangled audio-visual fusion framework that decomposes multimodal features into shared and specific representations. A trajectory constrained mechanism enhances representation purity, while a cross-modal attention-based dynamic fusion (CMF) module adaptively balances modality contributions, ensuring robust performance under real-world conditions. Experimental results demonstrate that DiVA achieves an AUC of 78.66% at the segment level and an accuracy of 79.46% at the subject level, significantly outperforming state-of the-art methods. With its cost-efficient and scalable de sign, it is well-suited for large-scale community screening, providing a practical solution for early dementia detection in resource-limited settings with considerable social and economic value.},
}

@article {pmid41915579,
year = {2026},
author = {Ashchi, A and Lachapelle, AA and Nassirou, S and Huston, J},
title = {Leqembi (Lecanemab) in Early Alzheimer's Disease: A Review of Clinical Trial Evidence and Therapeutic Implications.},
journal = {Reviews on recent clinical trials},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115748871418305260224075827},
pmid = {41915579},
issn = {1876-1038},
abstract = {Lecanemab is an IgG1 monoclonal antibody that has emerged as the first FDAapproved drug to slow the progression of Alzheimer's disease by targeting amyloid plaques, with the potential to serve as a disease-modifying therapy. Ongoing clinical studies are evaluating the efficacy and safety of the medication; however, much of the current literature remains mixed regarding the clinical effectiveness of lecanemab. The results from the Clarity AD study, the largest clinical study regarding the effectiveness of lecanemab to date, revealed a statistically significant 27% reduction in the progression of cognitive decline and favorable secondary endpoints in patients with mild cognitive impairment or mild dementia, particularly in male patients as well as heterozygous APOE4 carriers. However, approximately 21% of participants who received lecanemab treatment developed amyloid-related imaging abnormalities, with a higher incidence in homozygous APOE4 carriers. These findings highlight the need to thoroughly screen patients to confirm amyloid pathology with an amyloid PET scan or CSF biomarkers, and to determine APOE4 status before treatment. Additional barriers to care include the financial cost of the medication as well as the need to administer the drug intravenously at a healthcare facility to ensure proper management. Additional studies must continue to explore the clinical impact and safety of the medication and increase its accessibility. Future research may also include analyzing the utilization of the drug in combination therapies to optimize patient outcomes. This paper aims to provide a comprehensive review of current data on lecanemab, its clinical implications, and potential future directions for the use of lecanemab.},
}

@article {pmid41915835,
year = {2026},
author = {Davi, V and Parutto, P and Zhang, Y and Konno, T and Crapart, C and Pereira, R and Franklin, JP and Awadelkareem, MA and Maddison, DC and Devine, MJ and Gomes, ER and Chambers, J and Koslover, E and Avezov, E},
title = {Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e21101},
doi = {10.1002/advs.202521101},
pmid = {41915835},
issn = {2198-3844},
support = {UKDRI-2203//UK Dementia Research Institute/ ; /MRC_/Medical Research Council/United Kingdom ; 2034482//NSF/ ; grant AS-525 (AS-PhD 19a-015)//Alzheimer Society/ ; //Evelyn Trust/ ; },
abstract = {The endoplasmic reticulum (ER)'s continuous morphology is tightly controlled by ER-shaping proteins, whose genetic or expression defects drive a spectrum of neurodegenerative disorders from Hereditary Spastic Paraplegia to Alzheimer's disease. Why perturbations in ER morphology manifest specifically in neurons remains unknown. Here, by coupling visualisation of global sub-Hz firing bursts to ER ultrastructural manipulations in human inducible Pluripotent Stem Cells (hiPSC)-derived cortical neurons, alongside physical simulations, we establish a key ER structure-function principle: neuronal ER architecture dictates Ca[2+] replenishment speed. Altering ER structure hinders network ER luminal connectivity and Ca[2+] propagation from refill points at plasma membrane contact sites, impairing the ER's capability to supply repetitive Ca[2+] bursts. The ER morpho-regulatory control of Ca[2+] refill speed thus constitutes a switch on neuronal activity. Further, perturbed ER shape also abolishes Ca[2+] firing and contraction in primary skeletal muscle cells. These results expose the selective vulnerability of Ca[2+]-firing cells to ER structural disruptions, rationalizing ER dysfunction in neurodegeneration and unveiling a new role for the continuous ER morphology that could apply universally to Ca[2+]-firing cells.},
}

@article {pmid41915856,
year = {2026},
author = {Ge, J and Pagnon de la Vega, M and Zampar, S and Cerilli, E and Koutarapu, S and Wu, L and Fraser, P and Arkan, S and Giedraitis, V and Lannfelt, L and Hultqvist, G and Syvänen, S and Ingelsson, M and Hanrieder, J and Sehlin, D},
title = {The Uppsala APP Mutation Promotes Wild-Type Amyloid-β Aggregation and Deposition In Vivo.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14179},
doi = {10.1002/advs.202514179},
pmid = {41915856},
issn = {2198-3844},
support = {2016-02120//Swedish Research Council/ ; 2018-02715//Swedish Research Council/ ; 2019-02397//Swedish Research Council/ ; 2021-03524//Swedish Research Council/ ; 2023-02796//Swedish Research Council/ ; R01 AG078796/NH/NIH HHS/United States ; R21AG080705/NH/NIH HHS/United States ; PJT-173479//Canadian Institutes for Health Research/ ; AF-1032753//Alzheimerfonden/ ; AF-980959//Alzheimerfonden/ ; FO2025-0126//Hjärnfonden/ ; 253045//Konung Gustaf V:s och Drottning Victorias frimurarestiftelse, Stiftelsen Maja & J.P. Åhlén/ ; 2025-329//Stiftelsen för Gamla Tjänarinnor/ ; //Stohne's Stiftelse and Goljes stiftelse/ ; },
abstract = {Amyloid-β (Aβ) is widely regarded as a key initiator of theneurodegenerative cascade in Alzheimer's disease (AD).Studies of pathogenic mutations in the amyloid precursor protein (APP) genehave greatly advanced understanding of Aβ biochemistry, aggregation, anddeposition. One such mutation, Uppsala APP (APPUpp), produces AβUpp42Δ19-24, whichis highly aggregation-prone due to a six-amino-acid deletion in its central region.In both human APPUpp carriers and the recently developed tg-UppSwe mouse model, Aβ depositspredominantly consist of the human AβUpp mutant.However, whereas human carriers produce both wild-type Aβ (Aβwt) and AβUpp, tg-UppSwe mice express only AβUpp. To better mimic the human condition, weinvestigated the pathological interplay between Aβwt and AβUpp using in vitroco-aggregation assays and in vivo analyses in abitransgenic mouse model generated by crossing tg-UppSwe with tg-Swe mice. ELISA, immunohistochemistry, and MALDI mass spectrometry imaging revealed that earlydeposition of AβUpp42Δ19-24accelerates aggregation and deposition of Aβwt species (Aβwt38, Aβwt40, Aβwt42), likely through a seeding or catalytic mechanism. Notably, bitransgenic mice developed pronounced plaque-associated gliosisan alteration absent in tg-UppSwe animals. These findings suggest a synergistic interaction betweenAβUpp and Aβwt that may influence onset, progression, and structural featuresof Aβ plaques in APPUpp mutation carriers.},
}

@article {pmid41916096,
year = {2026},
author = {Kim, S and Jung, YC and Kim, E and Kim, KY and , },
title = {Right-lateralized cerebellar cortical thickening is associated with mild behavioral impairment in mild cognitive impairment.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100540},
doi = {10.1016/j.tjpad.2026.100540},
pmid = {41916096},
issn = {2426-0266},
abstract = {BACKGROUND: Mild Behavioral Impairment (MBI) reflects later-life emergence of persistent neuropsychiatric symptoms and is increasingly recognized as an early manifestation of neurodegenerative disease, yet cerebellar correlates remain underexplored. We tested whether cerebellar morphometry is associated with incident MBI in mild cognitive impairment (MCI).

METHODS: Using longitudinal Alzheimer's Disease Neuroimaging Initiative data, MBI was derived from Neuropsychiatric Inventory/ Neuropsychiatric Inventory-Questionnaire items mapped to five diagnostic domains and defined as new symptoms persisting for ≥2 consecutive visits after a symptom-free baseline. Of 530 MCI participants without baseline symptoms, 181 who developed MBI were matched 1:1 to controls by age, sex, and education. DeepCERES quantified lobular cerebellar cortical thickness and asymmetry from 3T T1-weighted MRI. We used logistic regression with false discovery rate correction and conducted domain-specific analyses (affective dysregulation, impulse dyscontrol, decreased motivation).

RESULTS: MBI cases had lower Mini Mental State Examination scores and higher dementia conversion than controls. Greater thickness in right cerebellar lobules IV (OR 1.215), V (OR 1.122), and VIIIB (OR 1.169), and greater asymmetry in right lobule V (OR 1.035), were associated with incident MBI. Affective dysregulation showed the strongest, largely right-lateralized associations and greater interhemispheric asymmetry. Main results were unchanged after separate sensitivity adjustments for Mini Mental State Examination scores and for index-visit psychiatric medication use.

CONCLUSION: Incident MBI in MCI is linked to right-lateralized cerebellar cortical thickening and asymmetry, most prominently for affective dysregulation. These patterns may reflect early compensatory and/or neuroinflammatory processes within cerebello-cortical circuits relevant to affect regulation.},
}

@article {pmid41916100,
year = {2026},
author = {Gong, H and Liu, J and Wang, Y and Lin, X and Wu, G and Ou, Y and Zhou, M and Yang, L and Peng, J and Ye, X and Wang, Y and Xu, F and Zhou, H and Feng, Z},
title = {Semaglutide treatment reverses HFD induced hippocampal microglia activation and improves cognitive dysfunction.},
journal = {Tissue & cell},
volume = {101},
number = {},
pages = {103495},
doi = {10.1016/j.tice.2026.103495},
pmid = {41916100},
issn = {1532-3072},
abstract = {Long-term high-fat diets (HFD) induce obesity, neuroinflammation, and cognitive decline, increasing Alzheimer's disease (AD) risk. This study explores whether Semaglutide, a GLP-1 receptor agonist, mitigates these effects by modulating microglia via IGFBPL-1 and the PI3K/AKT pathway. In HFD-fed C57/BL6 mice, Semaglutide improved cognitive function, reduced hippocampal microglia activation, and decreased AD-like pathology (phospho-Tau, Aβ). IGFBPL-1, a neuroprotective factor downregulated by HFD and restored by Semaglutide. Direct IGFBPL-1 supplementation replicated Semaglutide's benefits, while PI3K/AKT inhibition blocked them. These findings reveal IGFBPL-1 as a key mediator of Semaglutide's neuroprotection, offering novel insights into combating obesity-linked neurodegeneration.},
}

@article {pmid41916153,
year = {2026},
author = {Wang, C and Xu, X and Zhu, H and Wu, D and Liang, J and Wang, X and Song, R and Shen, L and Hu, Y and Wang, D and Zhu, H and Cheng, X and Qi, Y},
title = {Acori tatarinowii Rhizoma-Curcumae Radix herbal pair ameliorates cognitive impairment and suppresses neuro-inflammation via Ca[2+]/CaMKKβ/AMPK/mTOR pathway in Alzheimer's disease.},
journal = {Journal of ethnopharmacology},
volume = {365},
number = {},
pages = {121606},
doi = {10.1016/j.jep.2026.121606},
pmid = {41916153},
issn = {1872-7573},
abstract = {Effective activation of neuronal autophagy and clearance of amyloid-beta (Aβ) represents a promising therapeutic strategy in the treatment of Alzheimer's disease (AD). The Acori Tatarinowii Rhizoma-Curcumae Radix Herbal pair (ACHP), derived from the traditional Changpu Yujin Decoction, has a long history in Traditional Chinese Medicine for addressing conditions related to cognitive function. However, the precise mechanisms underlying its role in autophagic dysfunction-related dementia remain unclear.

AIM OF THE STUDY: This study aims to investigate the neuroprotective effects of ACHP and the underlying mechanisms in AD.

MATERIALS AND METHODS: Analysis of prototype constituents in drug-containing serum was performed using UHPLC-Triple-TOF/MS. The neuroprotective effects of ACHP were evaluated in APP/PS1 mice using behavioral tests, including the Y-maze and Morris water maze. Transcriptomic analysis was conducted to identify potential neuroprotective pathways activated by ACHP. Neuronal damage and structural recovery were assessed through HE and Nissl staining. In addition, the anti-inflammatory and autophagy-regulating effects of ACHP were further investigated in N2a/APP cells. The molecular mechanisms were further elucidated using Western blot, immunofluorescence, ELISA, and qRT-PCR in both in vivo and in vitro models.

RESULTS: Twenty-five compounds in ACHP-treated mouse serum were identified. ACHP improved spatial learning and memory performance, increased intracellular Ca[2+] levels and downregulated the expressions of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, while significantly promoting autophagy. ACHP increased CaMKKβ protein expression and activated the AMPK signaling pathway (elevated p-AMPK/AMPK ratio), as well as those of autophagy-related proteins, while improving neuronal morphology.

CONCLUSION: These findings indicate that ACHP alleviates neuro-inflammatory damage and cognitive impairment potentially through modulation of the Ca[2+]/CaMKKβ-AMPK-mTOR signaling pathway involved in autophagy.},
}

@article {pmid41916202,
year = {2026},
author = {Musrah, ATS and Nugraha, DY and Kumfor, F and Piguet, O},
title = {Unravelling cognition-Emotion mechanisms in Alzheimer's disease and frontotemporal dementia: A network analysis approach.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {199},
number = {},
pages = {60-82},
doi = {10.1016/j.cortex.2026.03.009},
pmid = {41916202},
issn = {1973-8102},
abstract = {Emotion processing deficits are common in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), yet few studies have examined how specific cognitive domains relate to emotion processing in these syndromes. This study investigated these relationships using network psychometrics. A total of 209 participants (56 AD, 55 bvFTD, 98 healthy controls) completed neuropsychological testing. Cognitive functions were assessed with the Addenbrooke's Cognitive Examination-III and the Sydney Language Battery, while emotion processing was measured with the Facial Affect Selection Task. Network models were estimated for each group and compared using the Network Comparison Test (NCT). Both patient groups showed impaired emotion recognition versus controls. Network density was highest in bvFTD (.62), followed by AD (.44), with controls showing the sparsest network (.16). In AD, emotion processing was associated with semantic comprehension and semantic knowledge, whereas in bvFTD, emotion processing related more closely to verbal fluency. Centrality indices supported these syndrome-specific patterns. NCT results showed no significant global differences in overall strength (St = .55, p = .411) or structure (Mt = .34, p = .529) between AD and bvFTD networks, indicating comparable overall organization despite differing functional roles of specific nodes. These findings suggest disease-specific cognitive-emotion associations: semantic mechanisms in AD and fluency-related mechanisms in bvFTD. Importantly, however, contributions of other cognitive processes, not measured here, are also plausible. Overall, the study highlights both shared and distinct patterns characterizing emotion processing impairments across dementias, offering insights for developing tailored interventions targeting syndrome-specific cognitive profiles.},
}

@article {pmid41916281,
year = {2026},
author = {Ellingford, R and Harris, SS and Kehring, M and Rajani, RM and Lam, FKW and Graykowski, D and Bӧken, D and Welikovitch, LA and Khasnavis, A and Laban, R and Heslegrave, A and Yaman, U and Mate de Gerando, A and Bond, SA and Wray, S and Salih, DA and Dupret, D and Dolan, RJ and Klenerman, D and Zetterberg, H and Hyman, BT and Busche, MA},
title = {Alzheimer's disease pathology degrades an NMDA receptor-dependent spontaneous activity pattern in cortico-hippocampal circuits.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.02.027},
pmid = {41916281},
issn = {1097-4199},
abstract = {Memory-based cognition relies on the integrity of cortico-hippocampal circuits, which are compromised in Alzheimer's disease (AD) as β-amyloid (Aβ) and tau accumulate. However, the mechanisms linking this pathology to circuit dysfunction remain unclear. In mouse models, using in vivo two-photon and Neuropixels recordings, we show that Aβ-tau pathology promotes both region- and layer-specific impairments, involving reduced burst firing in superficial cortical layers and CA1 and reduced mean firing of excitatory and inhibitory neurons in deep cortical layers and CA1. Exposure to Aβ primed the susceptibility of neuronal populations to tau-induced impairment. Combined Aβ-tau reduced synaptic NMDA receptor (NMDAR) density in both mouse and human tissue, while Aβ-tau co-reduction restored NMDARs and firing patterns and improved contextual memory. NMDAR antagonism in healthy mice phenocopied regional and laminar deficits. Our findings implicate synaptic NMDAR hypofunction as a reversible mechanism linking Aβ-tau synergy to cortico-hippocampal dysfunction in AD.},
}

@article {pmid41916283,
year = {2026},
author = {Ali, M and Timsina, J and Xu, Y and Chen, Y and Gong, K and Western, D and Heo, G and Liu, M and Budde, J and Pottier, C and Schindler, SE and Morris, JC and Holtzman, DM and Puerta, R and Cano, A and Boada, M and Fernandez, MV and Ruiz, A and Aguilar, M and Alvarez, I and Pastor, P and Perlmutter, JS and Campbell, MC and Kotzbauer, PT and Oh, HS and Wilson, EN and Guen, YL and , and , and , and , and , and , and Tarawneh, R and Wyss-Coray, T and Sung, YJ and Ibanez, L and Cruchaga, C},
title = {Large-scale CSF and plasma proteomics reveal immune, synaptic, and extracellular matrix disruptions across neurodegenerative diseases.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.02.035},
pmid = {41916283},
issn = {1097-4199},
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), share overlapping clinical and pathological features. We analyzed cerebrospinal fluid (CSF) and plasma proteomes from 2,705 and 3,009 samples, respectively, across these NDs, identifying disease-specific and shared molecular signatures. CSF showed more disease-associated proteins than plasma, with AD and DLB exhibiting the strongest cross-tissue similarity. Pathway analyses revealed shared dysregulation of immune-related processes in CSF and plasma across the NDs, as well as disease-specific impairment of glycosylation and apoptotic pathways in AD; ATF4 and PERK signaling in PD; fibroblast growth factor receptor (FGFR) and interleukin signaling in DLB; and glycoprotein hormones disruption in FTD. We developed disease-specific predictive models showing high accuracy (area under the curve [AUC]: 0.81-0.95 in CSF and 0.80-0.89 in plasma). These findings reveal distinct and convergent mechanisms across NDs, highlighting potential biomarkers and pathways for diagnostic and therapeutic strategies in neurodegeneration.},
}

@article {pmid41916306,
year = {2026},
author = {Hebisch, M and Kamin, V and Cenini, G and Piazzesi, A and Bertan, F and Weykopf, B and Schlee, J and Kaniyappan, S and Washicosky, KJ and Kim, DY and Bano, D and Peitz, M and Brüstle, O},
title = {Recapitulation of plaque formation, tau pathology, and neurodegeneration in a human 3D matrix model of Alzheimer's disease.},
journal = {Cell reports methods},
volume = {},
number = {},
pages = {101365},
doi = {10.1016/j.crmeth.2026.101365},
pmid = {41916306},
issn = {2667-2375},
abstract = {This study aims at implementing a 3D cell culture model of Alzheimer's disease (AD). To that end we engineered human induced pluripotent stem cell (iPSC)-derived neural stem cells to conditionally overexpress FAD mutant APP and PSEN1 variants. After differentiation in 3D basement membrane matrices, cultures exhibited increased Aβ42 and Aβ40 levels and a highly pathogenic shift of the Aβ42/40 ratio. Typical AD phenotypes such as amyloid deposition and tau pathology were observed alongside impaired mitochondrial integrity and neuronal damage. Pathophenotypes were ameliorated by γ-secretase inhibition, confirming amyloid toxicity as main driver of AD pathology. iPSC-derived microglia added to the cultures engulfed Aβ and apoptotic cells, underscoring the modularity of this experimental system. We expect our model to provide a useful tool for assessing the impact of amyloid reduction on downstream AD pathologies such as mitochondrial dysfunction, neuroinflammation, and neurodegeneration, in particular in light of recent progress in the development and use of amyloid-targeting drugs.},
}

@article {pmid41916355,
year = {2026},
author = {Medoro, A and Foderà, E and Ronci, M and Trerotola, M and Mignogna, D and Raimo, G and Intrieri, M and De Martino, A and Lepore, A and Porcile, C and Benincasa, T and Russo, C and Passarella, D},
title = {Generation and validation of C-terminal LRP8 antibodies for detecting processed intracellular fragments.},
journal = {BioTechniques},
volume = {78},
number = {1-12},
pages = {111-122},
doi = {10.1080/07366205.2026.2645347},
pmid = {41916355},
issn = {1940-9818},
mesh = {Humans ; *LDL-Receptor Related Proteins/immunology/metabolism/analysis/chemistry ; Reelin Protein ; Animals ; Mice ; Antibodies, Monoclonal/immunology ; *Antibodies/immunology ; Alzheimer Disease/metabolism ; Immunohistochemistry/methods ; },
abstract = {Introduction: Low-density lipoprotein receptor-related protein 8 (LRP8) is a neuronal receptor for apolipoprotein E and Reelin, two ligands critically involved in Alzheimer's disease (AD), neuronal migration, and memory. Because LRP8 is highly expressed in neurons, interacts with amyloid precursor protein, and undergoes γ-secretase-dependent processing, it has emerged as a potential contributor to AD-related neurodegeneration. Growing evidence also implicates LRP8 in carcinogenesis, highlighting the need to better define its molecular properties. Areas covered: This article addresses the limited understanding of LRP8 proteolytic processing, cellular localization, and molecular interactions, due in part to the lack of suitable antibodies. We present and characterize novel polyclonal and monoclonal antibodies directed against the C-terminal region of LRP8, suitable for Western blotting and immunocytochemistry/immunofluorescence. These reagents enabled detection of a previously unrecognized intracellular low-molecular-weight (∼12 kDa) C-terminal LRP8 fragment. Expert opinion/Commentary: These antibodies provide valuable new tools for mechanistic studies of LRP8. By improving the investigation of LRP8 processing and localization, they may facilitate a better understanding of its role in neurodegeneration and cancer.},
}

Humans
*LDL-Receptor Related Proteins/immunology/metabolism/analysis/chemistry
Reelin Protein
Animals
Mice
Antibodies, Monoclonal/immunology
*Antibodies/immunology
Alzheimer Disease/metabolism
Immunohistochemistry/methods

@article {pmid41916432,
year = {2026},
author = {Liu, H and Zhong, XC and Xiong, J and Zhou, L and Zeng, SQ and Wang, HB and Li, ZQ},
title = {Efficacy and acupoint specificity of sedative-tranquilizing acupuncture for Alzheimer's disease with sleep disorders: a three-arm randomized controlled trial protocol.},
journal = {Complementary therapies in medicine},
volume = {},
number = {},
pages = {103366},
doi = {10.1016/j.ctim.2026.103366},
pmid = {41916432},
issn = {1873-6963},
abstract = {OBJECTIVES: Sleep disorders (SD) are highly prevalent in patients with Alzheimer's disease (AD); however, effective pharmacological interventions are often limited by adverse effects or insufficient efficacy. This study aims to evaluate the clinical synergistic value and the "sleep-cognition co-modulation" effect of sedative-tranquilizing acupuncture, a specialized non-pharmacological therapy, in managing AD-SD comorbidity.

PARTICIPANTS AND METHODS: This is a multicenter, randomized, controlled trial (RCT) involving 72 participants diagnosed with both AD and SD. Participants will be randomly assigned (1:1:1) to one of three groups: the control group, receiving standard care (donepezil hydrochloride combined with cognitive behavioral therapy for insomnia [CBT-I]); the acupuncture group, receiving sedative-tranquilizing acupuncture in addition to standard care; and the sham acupuncture group, receiving sham acupuncture plus standard care. The primary outcome measure is the change from baseline in the Pittsburgh Sleep Quality Index (PSQI) score. Secondary outcomes include cognitive function (Mini-Mental State Examination [MMSE]), quality of life (Quality of Life in Alzheimer's Disease [AD-QOL] scale), and psychological symptoms (Hamilton Anxiety Scale [HAMA] and the 17-item Hamilton Depression Scale [HAMD-17]). Furthermore, peripheral biochemical markers, polysomnography (PSG) parameters, and neuroimaging data will be analyzed to explore underlying mechanisms. All analyses will be performed on an intention-to-treat (ITT) basis.

CONCLUSIONS: This trial is expected to provide robust clinical evidence regarding whether sedative-tranquilizing acupuncture can effectively assist in improving sleep quality and cognitive function in patients with AD-SD comorbidity. The findings will further elucidate the potential neurobiological mechanisms of acupuncture and offer a novel integrative strategy for the management of AD-related sleep disturbances.

TRIAL REGISTRATION: This protocol was approved by the Ethics Committee of Nanchang Hongdu Hospital of Traditional Chinese Medicine (KYKS-2024044-1(X-2) and registered with the International Traditional Medicine Clinical Trial Registry (https://itmctr.ccebtcm.org.cn/mgt/project/user/user-project-view/09DB9DBC-F576-4AF9-AF4E-D6D88E1B1B6B).},
}

@article {pmid41916755,
year = {2026},
author = {Luthra, NS and Bonham, LW and Moreno, AJ and Park, C and Huguenard, CJC and Abdulai-Saiku, S and Gupta, S and Lin, J and Broestl, L and Bétourné, A and Sehgal, R and Wang, D and Lesné, SE and Ostrem, JL and Yokoyama, JS and Dubal, DB},
title = {Longevity factor klotho and resistance to cognitive deficits in individuals with Parkinson's disease and in an α-synuclein mouse model.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1904-25.2026},
pmid = {41916755},
issn = {1529-2401},
abstract = {Aging is the primary risk factor for Parkinson's disease (PD) and PD-related cognitive impairment remains a major unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition, but whether it confers resilience to cognitive impairments in PD is unclear. Here, we show that in humans, the KL-VS genetic variant of KLOTHO, linked to higher circulating klotho levels, associated with better executive cognition in individuals with PD across two independent cohorts. To test causality and explore mechanisms, we turned to mouse models. Transgenic elevation of klotho in a mouse model increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein (α-syn) levels in the brains of male mice expressing wildtype human α-syn. Complementary in vitro studies showed that klotho rescued α-syn-induced deficits in NMDAR-dependent signaling through GluN2B and augmented α-syn microglial-related uptake, suggesting a potential mechanism by which klotho counters PD-related toxicity. Together, these findings indicate that klotho can counteract cognitive deficits related to PD, possibly by modulating α-syn levels - and these findings may be relevant to new therapeutic pathways for PD.Significance statement Klotho is a longevity factor that improves cognition in old mice, Alzheimer's disease model mice, and old nonhuman primates, yet its role Parkinson's disease (PD)-related cognitive impairment remains unclear. Here, we identified an association between a KLOTHO variant and executive cognitive function in PD, a cognitive domain preferentially affected by the disease. To investigate biological mechanisms of klotho, we leveraged an α-synuclein mouse model of PD and found that klotho decreased cognitive deficits, potentially by increasing synaptic plasticity and reducing α-synuclein levels. Together, these findings suggest that klotho modulates PD-related cognitive deficits and highlight klotho-based strategies as promising therapeutic pathways for cognitive impairment in PD and other α-synucleinopathies.},
}

@article {pmid41916866,
year = {2026},
author = {Chen, C and Zhou, M and Tang, L},
title = {Comment on "Alzheimer's disease diagnosis: An update and review of biomarkers, positron emission tomography, and emerging therapies".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.03.102},
pmid = {41916866},
issn = {0929-6646},
}

@article {pmid41916957,
year = {2026},
author = {Raulin, AC and Alnobani, A and Rodriguez-Martinez, P and Lee, E and Linares, C and Yslas, AR and Li, M and Ren, Y and Doss, SV and Roy, B and Kuchenbecker, LA and Martens, YA and Liu, CC and Bu, G and Kanekiyo, T},
title = {Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.},
journal = {Translational psychiatry},
volume = {16},
number = {1},
pages = {},
pmid = {41916957},
issn = {2158-3188},
support = {U19AG069701//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG071226//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG068034//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG057181//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; RF1AG081203//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; A2021015F//BrightFocus Foundation (BrightFocus)/ ; },
mesh = {Animals ; *Astrocytes/metabolism ; *Alzheimer Disease/genetics/pathology/metabolism ; *Amyloid beta-Peptides/metabolism ; Mice ; Mice, Transgenic ; Disease Models, Animal ; *Brain/metabolism/pathology ; *Apolipoprotein E3/genetics/metabolism ; Plaque, Amyloid/pathology/metabolism ; Humans ; },
abstract = {The rare APOE3-Christchurch (APOE3Ch) variant is linked to resistance against PSEN1 p.E280A-driven autosomal dominant Alzheimer's disease (AD). Recent studies in AD mouse models have demonstrated an effect of APOE3Ch in reducing tau pathology and tau propagation, yet its effects on amyloid pathology and related toxicity are not fully understood. While prior studies have reported reduced amyloid pathology with APOE3Ch, we extended this knowledge by investigating how astrocyte-specific expression of APOE3Ch impacts amyloid pathology and related responses in 5xFAD mice, an amyloid mouse model. Using adeno-associated virus (AAV)-mediated gene delivery, we overexpressed APOE3 or APOE3Ch in astrocytes of 5xFAD mice at the neonatal stage, then analyzed their effects during the advanced stage of amyloid pathology. Astrocytic APOE expression significantly reduced amyloid burden, neuritic dystrophy, and gliosis compared to GFP controls. Notably, astrocytic APOE3Ch expression, relative to APOE3, markedly lowered oligomeric Aβ levels and promoted the formation of more compact, fibrillar plaques, suggesting a shift toward a less toxic aggregation profile. Transcriptomic profiling of cortical tissue revealed broad downregulation of immune-related and proteostatic pathways. These findings indicate that astrocytic APOE3Ch sufficiently attenuates Aβ pathology and related toxicity, supporting its potential as a therapeutic modifier for AD.},
}

Animals
*Astrocytes/metabolism
*Alzheimer Disease/genetics/pathology/metabolism
*Amyloid beta-Peptides/metabolism
Mice
Mice, Transgenic
Disease Models, Animal
*Brain/metabolism/pathology
*Apolipoprotein E3/genetics/metabolism
Plaque, Amyloid/pathology/metabolism
Humans

@article {pmid41916976,
year = {2026},
author = {Parent, O and Alasmar, Z and Osborne, S and Bussy, A and Costantino, M and Fouquet, JP and Quesada, D and Pastor-Bernier, A and Fajardo-Valdez, A and Pichet-Binette, A and McQuarrie, A and Maranzano, J and Devenyi, GA and Steele, CJ and Villeneuve, S and , and , and Dadar, M and Chakravarty, MM},
title = {Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70832-2},
pmid = {41916976},
issn = {2041-1723},
abstract = {White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.},
}

@article {pmid41917225,
year = {2026},
author = {Bonuck, K and Gao, Q and Congdon, S and Kim, RS},
title = {Long COVID disability burden in US adults.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {41917225},
issn = {2730-664X},
abstract = {BACKGROUND: Five years since the scientific and patient communities first identified the syndrome now known as Long COVID, affected individuals lack treatments, and the US lacks population-based data on its disability burden and correlation with National Institutes of Health (NIH) funding. Moreover, akin to other debilitating conditions it often co-occurs with, e.g., Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia, Long COVID disproportionately impacts females whose concerns are often marginalized.

METHODS: We quantify Long COVID years lived with disability (YLDs= prevalence x disability weight) in US adults and its actual/YLD-commensurate average annual NIH FY2022-2024 funding versus 68 comparator conditions, by sex predominance. We derive Long COVID prevalence from Census Bureau surveys (9/2022-8/2023) and apply disability weights from the Global Burden of Disease Study.

RESULTS: Long COVID YLDs approximate those of Alzheimer's and Asthma. Long COVID received 14% of its disability commensurate funding: $106 million vs. $739.8 million. ME/CFS is the most under-funded condition, receiving <1% of its YLD proportionate funding. Among conditions analyzed, 24 are female-predominant (we estimate Long COVID funding two ways), 12 male-predominant, and 33 show no sex predominance. Among the 12 below-median funded/above-median YLD conditions, 7/12 are female-predominant, none are male-predominant. Median funding/per YLD is 5.2 times higher for male- vs. female-predominant conditions (7.0 vs 1.3 million per YLD, p = 0.007). Overall, YLDs explain 6.5% of funding variance in a linear regression model using YLD as the sole predictor (Adjusted R-squared: 0.065).

CONCLUSIONS: With chronic conditions like Long COVID rising, disability burden merits greater consideration in funding decisions, as does biological sex.},
}

@article {pmid41917388,
year = {2026},
author = {Tachida, Y and Kitazume, S},
title = {Unique Expression and Glycosylation of Amyloid Precursor Protein in Alzheimer's Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1491},
number = {},
pages = {33-42},
pmid = {41917388},
issn = {0065-2598},
abstract = {Accumulation of amyloid β (Aβ) peptide in the brain is a characteristic pathological feature of Alzheimer's disease that occurs several decades before the onset of symptoms. Aβ is produced from the membrane-bound amyloid β precursor protein (APP) by β-secretase 1 (BACE1) and γ-secretase-mediated proteolytic cleavage. Alternatively, ADAM10/17 α-secretase and γ-secretase cleavage does not generate Aβ. Accumulating evidence indicates that intracellular trafficking of APP to each secretase determines the level of Aβ production. In this chapter, we summarize how glycosylation affects the Aβ production, possibly by modulating the intracellular localization of APP and its secretases.},
}

@article {pmid41917389,
year = {2026},
author = {Hane, M and Abe, C and Kitajima, K and Sato, C},
title = {Relationship Between Regulation of Polysialic Acid Expression and Brain Diseases.},
journal = {Advances in experimental medicine and biology},
volume = {1491},
number = {},
pages = {43-56},
pmid = {41917389},
issn = {0065-2598},
abstract = {This chapter reviews the relationship between polysialic acid (polySia), its biosynthetic enzyme ST8SIA2, and brain diseases, particularly psychiatric disorders such as schizophrenia, bipolar, and autism spectrum disorders, as well as neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. We also focus on the connection between inflammation and the polySia degradation enzyme, sialidase (neuraminidase).},
}

@article {pmid41907405,
year = {2026},
author = {Wei, Z and Zhou, X and Li, B and Gu, J and Ge, L and Tang, F and Lin, M and Jin, Y},
title = {Comparative analyses of regional and temporal transcriptomics of early human and mouse central nervous systems.},
journal = {iScience},
volume = {29},
number = {4},
pages = {115222},
pmid = {41907405},
issn = {2589-0042},
abstract = {The unique gene expression program driving early human brain development remains incompletely defined. In this study, we profile and compare transcriptomes of human and mouse embryo central nervous system (CNS) across Carnegie stages (CS) 11-14, a critical window spanning neural tube closure to early brain regionalization, including 4 CNS regions at CS13-14. Our analysis reveals that human CNS is less mature than mouse CNS at CS13-14. Extracellular matrix (ECM) organization/structure emerges as the most divergent biological process, underscoring species-specific ECM roles in early CNS development. Co-expression module analysis reveals CS14 as the most conserved stage, CS12-13 as the most divergent, and CS11 as encompassing both conserved and species-specific events. Early spinal cord development shares regulatory mechanisms between species. This study uncovers previously unrecognized spatiotemporal/species-specific gene expression features, offering a valuable resource for Alzheimer's disease (AD) developmental origin research and highlighting ECM pathways as promising regenerative medicine targets.},
}

@article {pmid41907455,
year = {2026},
author = {Hanes, DW and Clouston, SAP},
title = {Cognitive Aging in the Context of the Housing Crisis: Trends and Evidence From the Health and Retirement Study.},
journal = {Canadian studies in population},
volume = {53},
number = {1},
pages = {4},
pmid = {41907455},
issn = {0380-1489},
abstract = {UNLABELLED: The 21st Century has witnessed a global housing crisis, which is also occurring in the context of population aging. We hypothesized that housing instability may expose older adults to greater risk factors for onset of Alzheimer's disease and related dementias (ADRD). Using the Health and Retirement Study (HRS), a population-based study of older US adults, we analyzed whether changes to older adults' housing patterns were associated with earlier onset of accelerated cognitive decline consistent with ADRD. We first replicated results showing that renting is becoming more common over time in older adults, while homeownership is becoming less common both in subsequent years and among later-born cohorts. Next, using non-linear multivariate analyses we found, in separate analyses, that renting, moving more frequently, living with non-partner others, and greater housing stress were all associated with earlier onset of accelerated cognitive decline indicative of ADRD. Given the growing population of older adults, this study suggests that the housing crisis may also cause worsened cognitive health in old age. More research is warranted to determine whether other markers of housing affordability or quality might be associated with accelerated cognitive decline in older adults.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42650-026-00108-z.},
}

@article {pmid41907517,
year = {2026},
author = {Patoine, C and Sheffler, J and Sims, T and Gutierrez, V and Park, G and Mayonu, M and Wang, B and Nagpal, R},
title = {Obesity-associated gut microbiome influences diet-induced metabolic and cognitive outcomes in older adults.},
journal = {Gut microbes reports},
volume = {3},
number = {1},
pages = {2605879},
pmid = {41907517},
issn = {2993-3935},
abstract = {Obesity in older adults is a known risk factor for Alzheimer's disease and related dementias, potentially driven by metabolic dysfunction, inflammation and gut dysbiosis. The gut-brain axis, influenced by diet and the gut microbiome, is increasingly recognized as a contributor to neurodegeneration. In this sub-analysis of a 10-week randomized dietary education intervention (NCT06121986), we examined how obesity modulates gut microbiome, metabolome, and cognitive responses in 31 adults aged 55-85, with or without mild cognitive impairment. Participants received education on either a Mediterranean Diet or a Modified Mediterranean-Ketogenic Diet. Analyses were stratified by baseline obesity (BMI ≥30 kg/m[2]). Individuals with obesity exhibited lower microbial alpha-diversity, higher Bacteroides, and lower Akkermansia and Christensenellaceae_R-7_group, along with poorer memory and executive function. Only in the obese group did fat loss correlate with improvements in episodic memory and cognitive flexibility. In contrast, increased fat mass was associated with improved memory in non-obese participants. Gains in skeletal muscle mass predicted cognitive improvement in adults aged ≥73. Changes in gut (acetate, propionate, lactate) and plasma (acetate, pyruvate, citric acid) metabolites were linked to cognitive and body composition outcomes. These exploratory findings highlight the gut-muscle-brain axis as a modifiable target to enhance cognitive health in aging populations.},
}

@article {pmid41907581,
year = {2026},
author = {Kearney, S and Yang, S and Wen, Z and Lyu, W and Hou, B and Duong-Tran, D and Chen, T and Moore, JH and Ritchie, MD and Chen, C and Shen, L},
title = {Tabular LLMs for Interpretable Few-Shot Alzheimer's Disease Prediction with Multimodal Biomedical Data.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41907581},
issn = {2331-8422},
abstract = {Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.},
}

@article {pmid41907842,
year = {2026},
author = {Alhusaini, M and Mussa, BM and Ilce, BY and Alhaj, H and Hamoudi, R},
title = {Molecular mechanism of Alzheimer's disease using integrated multi-omics.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1735696},
pmid = {41907842},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD) is a devastating neurodegenerative disorder driven by complex interactions between neuroinflammation, immune dysregulation, metabolic impairment, and disrupted synaptic plasticity. Emerging evidence highlights maladaptive microglial activation, chronic cytokine signaling (including IL-1β, TNF-α, and IL-6), and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity as pivotal contributors to neuronal damage and cognitive decline. Genetic studies further underscore the importance of immune and metabolic pathways, implicating key risk genes such as APOE, TREM2, and CR1, while deficits in autophagy exacerbate pathological protein aggregation, including amyloid-β and tau, ultimately accelerating synaptic loss. In this review, we synthesize molecular, genetic, and cellular evidence to clarify the mechanisms driving AD pathogenesis. We discuss genome-wide association study (GWAS) findings that define the genetic architecture of the disease, the neuroimmune crosstalk affecting memory-related brain regions, the link between chronic stress and amyloid pathology through HPA-axis dysregulation, and metabolic reprogramming in neurons, astrocytes, and microglia. Together, these interconnected processes highlight how dysregulated immunity and impaired protein clearance contribute to neuronal dysfunction and the progressive cognitive decline characteristic of AD.},
}

@article {pmid41907843,
year = {2026},
author = {Yu, Y and Wang, Y and Guo, S and Zhang, J and Bai, Y and Liu, C and Liu, X and Li, X and Jiang, X and Liu, P and Ling, J and Zhao, J and Tang, C and Rong, P},
title = {40-Hz transauricular vagal nerve stimulation rescues cognition of 9-month-old APP/PS1 mice via inhibiting hippocampal P2X7 receptor signaling.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1766813},
pmid = {41907843},
issn = {1663-4365},
abstract = {The lack of any viable therapy for Alzheimer's disease (AD) evoked the study and utilization of neuromodulation. 40-Hz transauricular vagal nerve stimulation (taVNS) preliminarily showed effectiveness in mice with partial cognitive impairment in our previous work, yet 3 major problems remained unresolved. (1) Can 40-Hz taVNS rescue the cognition of mice exhibiting total cognitive impairment? (2) Are the cognition-rescuing effects of taVNS specific to 40 Hz stimulation? (3) Via P2X7R signaling? Thus, 3 parts were divided to address the above issues in this work using 9-month-old wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice. Behavioral examinations for cognition; western blotting (WB), enzyme-linked immunosorbent assays (ELISA) for Aβ load; WB and ELISA for the P2X7R signaling pathway; Nissl staining for neuroprotective effects were employed. 3 findings can be derived. (1) 40-Hz taVNS rescues cognition of the APP/PS1 mice aged 9 months (but is not effective in WT mice of the same age). (2) The cognition-rescuing effects of taVNS in APP/PS1 mice are frequency-specific, which is 40 Hz in this work (neither 8-Hz taVNS nor 80-Hz taVNS works). (3) The hippocampal P2X7R signaling is a critical mediator of the observed effects (inhibiting P2X7R had similar effects to 40-Hz taVNS, which counteracted activating P2X7R). Therefore, 40-Hz taVNS shows potential as a viable therapy option for AD, with the P2X7R being a prominent target.},
}

@article {pmid41907844,
year = {2026},
author = {Qu, G and Bi, Y and Wang, L and Xu, L and Zhang, Y and Ma, Y and Tian, C and Zhang, Z},
title = {Efficacy of Dang Gui Shao Yao San in treating vascular dementia in animal models: a systematic review and meta-analysis.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1701536},
pmid = {41907844},
issn = {1663-4365},
abstract = {BACKGROUND: Vascular dementia (VaD) is the second most prevalent form of dementia, following Alzheimer's disease (AD), and severely impacts life quality of patients. Currently, effective strategies to alleviate symptoms and delay disease progression remain unavailable. Animal studies indicate that Dang Gui Shao Yao San (DGSYS) may enhance cognitive function in VaD models through mechanisms such as antioxidation and the enhancement of cerebral blood flow. However, a systematic review of its neuroprotective effects and a comprehensive assessment of its translational potential in preclinical models are still lacking.

OBJECTIVE: This study seeks to synthesize evidence on the intervention effects and underlying mechanisms of DGSYS in animal models of VaD through a systematic review and meta-analysis, so as to offer preclinical evidence to inform future research.

METHODS: A comprehensive literature search was performed across eight databases: China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, Wanfang Data, SinoMed, Web of Science, Cochrane Library, PubMed, and EMBASE, to identify studies published from the inception to May 2025 on the effects of DGSYS in animal models of VaD. The primary outcomes were cognitive and behavioral assessments, histopathological alterations in brain tissue, and biomarkers of oxidative stress. The quality of the included studies was assessed using a 10-item checklist, and meta-analysis was conducted with RevMan 5.4 software.

RESULTS: Seven studies involving 420 rats and mice were included. DGSYS notably enhanced cognitive and behavioral performance in the animal models. Specifically, DGSYS significantly improved spatial learning and memory performance, as assessed by the Morris water maze, and attenuated oxidative stress-related pathological changes.

CONCLUSION: Current animal studies provide evidence for the multidimensional neuroprotective effects of DGSYS in VaD, with potential mechanisms involving antioxidative stress, inhibition of neuroinflammation, and enhancement of cerebral microcirculation. However, substantial heterogeneity across outcome measures and generally low methodological quality were observed. Overall, the available evidence suggests potential neuroprotective effects of DGSYS in preclinical models, warranting further standardized and rigorously designed studies before clinical translation can be considered.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251058443, identifier CRD420251058443.},
}

@article {pmid41907848,
year = {2026},
author = {Li, Q and Zhao, R and Tian, X and Xu, H},
title = {Molecular mechanisms underlying exercise-enhanced autophagy in improving neuroplasticity in Alzheimer's disease.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1780247},
pmid = {41907848},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by progressive memory impairment and cognitive dysfunction. The neuropathological hallmarks of this neurodegenerative disorder encompass two principal pathological features: extracellular deposition of amyloid-β (Aβ) plaques due to abnormal protein aggregation, and intracellular accumulation of neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau proteins (p-Tau). These pathological changes induce synaptic loss and neuronal apoptosis, which leads to impaired neuroplasticity and progressive deterioration of cognitive function. Autophagy, a critical mechanism in the central nervous system (CNS) responsible for clearing misfolded protein aggregates and damaged organelles, plays a pivotal role in maintaining neuronal homeostasis and synaptic plasticity. However, AD is associated with autophagy impairment, resulting in the accumulation of toxic protein aggregates and damaged organelles. These pathological changes disrupt protein homeostasis, thereby exacerbating neurodegenerative processes. Currently, AD therapeutic strategies remain limited. Emerging evidence indicates that exercise intervention mitigates cognitive decline and enhances synaptic plasticity, potentially through reducing Aβ deposition and pathological phosphorylation of tau proteins. However, the precise mechanisms through which these interventions act remain to be fully elucidated. Recent studies have shown that exercise can promote autophagosome formation, fusion, and lysosomal hydrolytic function, thereby ameliorating the pathological progression of AD. Despite these promising findings, the precise molecular targets and underlying signaling mechanisms through which exercise modulates autophagy in AD remain to be fully elucidated. The purpose of this study is to establish innovative therapeutic targets while identifying mechanistically actionable pharmacological targets to advance therapeutic development against AD pathogenesis.},
}

@article {pmid41907849,
year = {2026},
author = {Tavares, TG and Carvalho, I and Ramalho, MJ and Andrade, S and Pereira, MC and Loureiro, JA},
title = {Solid lipid nanoparticles as carriers for Ulva rigida peptide extract with demonstrated anti-β-amyloid and antioxidant properties.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1778124},
pmid = {41907849},
issn = {1663-4365},
abstract = {INTRODUCTION: Alzheimer's disease (AD) remains one of the greatest challenges in neurodegenerative research, largely due to the toxic aggregation of the β-amyloid (Aβ) peptide and the difficulty of delivering therapeutic compounds across the blood-brain barrier (BBB).

METHODS: This work explored Ulva rigida (U. rigida), a green macroalga rich in bioactive peptides, as a natural source of anti-amyloidogenic and antioxidant agents.

RESULTS: First, the peptides extraction process was optimized by design of experiments (DoE). Peptides extracted and hydrolyzed under optimized conditions showed antioxidant capacity (2.51 ± 0.18 μmolTrolox equivalent/ mghydrolyzed protein), and the fraction of peptides with a molecular weight lower than 3 kDa was able to reduce the aggregation of Aβ 1-42 peptide in vitro by around 60%. To overcome the issue of limited bioavailability, we encapsulated these peptides in solid lipid nanoparticles (SLNs). The developed nanoformulation displayed a size of 158 ± 14 nm, narrow polydispersity, and near-neutral zeta potential (-4.7 ± 0.6 mV), with an encapsulation efficiency (EE) of 54.1 ± 0.1% and suitable stability under simulated gastrointestinal and storage conditions.

DISCUSSION: By combining biological activity with a delivery platform, this study highlights the potential of Ulva rigida as a source of bioactive peptides with the potential to delay the progression of AD.},
}

@article {pmid41908279,
year = {2026},
author = {Alqarni, A and Alkhybari, E and Alshuhri, MS and Aljuhani, M and Hadadi, I and Alosaimi, MH and Alshaari, H and Alqahtani, MM and Abd-Elghany, AA and , },
title = {Sex-specific effect of cortisol on cerebral glucose metabolism across Alzheimer's disease spectrum: a neuroimaging study.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1680116},
pmid = {41908279},
issn = {1664-2295},
abstract = {Higher levels of cortisol can disrupt the normal patterns of cerebral glucose metabolism in the human brain. This study aims to investigate the effects of elevated cortisol levels on cerebral glucose metabolism in men and women across Alzheimer's disease spectrum. The data was derived from the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Eight hundred and twenty-two participants across varying diagnostic cognition status were included: 469 men (mean age of 74.14 ± 7.19 years) and 353 women (mean age of 72.31 ± 7.34 years). Main effect and interaction terms were used in generalized linear models to examine the association between elevated cortisol levels and cerebral glucose metabolism as measured by Fluorodeoxyglucose positron emission tomography (FDG-PET) in men and women across Alzheimer's disease spectrum. Sex-stratified analysis was conducted a priori based on established biological differences in HPA axis function between sexes. Elevated cortisol levels were negatively associated with brain glucose consumption in women, but not in men. Women with APOE4 alleles were at greater risk of brain hypometabolism. Diastolic blood pressure in men, but not women, was negatively associated with brain glucose consumption, an indication of higher vascular vulnerability in men. Notably, while sex-stratified analyses revealed these differential patterns, the formal cortisol[*]sex interaction term did not reach statistical significance (p = 0.157), potentially due to limited statistical power for detecting interactions. Larger studies are warranted to confirm these sex-specific findings. These findings suggest that cortisol may represent a modifiable risk factor warranting further investigation, particularly in postmenopausal women who experience estrogen decline, a known neuroprotective mediator.},
}

@article {pmid41908685,
year = {2026},
author = {Maddox, S and Puglisi, L and Darabifard, F and , and Sami, S and Ravi, D},
title = {Regional patch-based MRI brain age modeling with an interpretable cognitive reserve proxy.},
journal = {Pattern recognition letters},
volume = {199},
number = {},
pages = {219-224},
pmid = {41908685},
issn = {0167-8655},
abstract = {Accurate brain age prediction from MRI is a promising biomarker for brain health and neurodegenerative disease risk, but current deep learning models often lack anatomical specificity and clinical insight. We present a regional patch-based ensemble framework that uses 3D Convolutional Neural Networks (CNNs) trained on bilateral patches from ten subcortical structures, enhancing anatomical sensitivity. Ensemble predictions are combined with cognitive assessments to derive a cognitively informed proxy for cognitive reserve (CR-Proxy), quantifying resilience to age-related brain changes. We train our framework on a large, multi-cohort dataset of healthy controls and test it on independent samples that include individuals with Alzheimer's disease and mild cognitive impairment. The results demonstrate that our method achieves robust brain age prediction and provides a practical, interpretable CR-Proxy capable of distinguishing diagnostic groups and identifying individuals with high or low cognitive reserve. This pipeline offers a scalable, clinically accessible tool for early risk assessment and personalized brain health monitoring.},
}

@article {pmid41908799,
year = {2025},
author = {Feng, JX and Zheng, MQ and Tian, X and Zimmermann, A and Wang, AX and Meng, X},
title = {Ginkgo biloba extract EGb 761 in patients with dementia and a history of cerebral infarction-meta-analysis of pooled data from randomised clinical trials.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1658064},
pmid = {41908799},
issn = {1664-2295},
abstract = {INTRODUCTION: Ginkgo biloba leaf extracts belong to the most popular herbal medicines for the treatment of neurological disorders, including Alzheimer's disease (AD) or stroke. EGb 761, a proprietary ginkgo leaf extract, has been shown to improve brain cell energy supply, to enhance neurogenesis and neuroplasticity, to decrease blood viscosity and improve brain perfusion. Thereby it improves cognitive performance, neuropsychiatric symptoms and activities of daily living in patients with dementia or mild cognitive impairment. It has further been shown to be beneficial for patients after ischaemic stroke. Therefore, the aim of this meta-analysis was to evaluate the treatment effects of EGb 761 in patients who had developed dementia following a cerebral infarction.

METHODS: We performed a meta-analysis of pooled data from clinical trials with EGb 761 in mild to moderate dementia in the subgroup of patients who had a cerebral infarction. Four randomised, placebo-controlled trials with homogeneous patient selection and design were included. Previous stroke was diagnosed by neuroimaging. The analysis focused on the comparison of treatment effects in the domains of cognition, activities of daily living and global assessment.

RESULTS: The meta-analysis included data from 488 patients. Significant treatment effects of 240 mg EGb 761 daily versus placebo were found for cognition (p = 0.0467), activities of daily living (p = 0.0230), and global clinical impression (p = 0.0371). The rates of adverse events and adverse drug reactions in the EGb 761 group were like those in the placebo group.

CONCLUSION: The results of our meta-analysis of patients with mild to moderate dementia who had previously had a cerebral infarction verified by neuroimaging showed statistically significant and clinically relevant benefits of EGb 761. The drug was shown to be safe and well tolerated and is a promising treatment option for patients developing dementia after cerebral infarction. Further dedicated clinical trials are needed to confirm these results.},
}

@article {pmid41909127,
year = {2026},
author = {Sabbir, MG},
title = {Editorial: Cellular and molecular pathologies of Alzheimer's disease: understanding the link between different etiological factors for therapeutic exploitation.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1813923},
pmid = {41909127},
issn = {2296-634X},
}

@article {pmid41909487,
year = {2026},
author = {Gowdy, J and Ahn, J and Miller, RH and Islam, Y},
title = {Neurovascular dysfunction in the development and progression of neuroinflammatory diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1741928},
pmid = {41909487},
issn = {1662-5102},
abstract = {The neurovascular unit (NVU) is critical for brain homeostasis through its roles in maintenance of an effective blood brain barrier (BBB) and regulation of cerebral blood flow. Perturbation of the NVU is a hallmark of the pathology of multiple neurodegenerative diseases resulting in loss of BBB integrity, neuroinflammation and neuronal dysfunction. The NVU is a complex structure composed of endothelial cells, pericytes, as well as central nervous system (CNS) glial and neuronal components. While the importance of the CNS vasculature in health and disease is well established, the mechanisms underlying vascular pathology and its contributions to neurodegenerative diseases are less well defined. Neuroinflammation and reactive gliosis occurs in the majority of neurodegenerative diseases and recent studies suggest that immune mediated disruption of the BBB contributes to the induction of reactive gliosis and neuronal dysfunction. Potential consequences of NVU disruption include immune-driven vascular inflammation and leukocyte infiltration in Multiple Sclerosis (MS), protease-mediated tight junction degradation in ischemic stroke (IS), α-synuclein-associated endothelial dysfunction in Parkinson's Disease (PD), amyloid-β- and tau-induced pericyte injury in Alzheimer's Disease (AD), and complement-mediated vascular damage in Amyotrophic Lateral Sclerosis (ALS). Here we review the nature of NVU perturbations in these common neurodegenerative diseases, with an emphasis on the contribution of immune modulation of BBB disruption in neuropathology and disease progression.},
}

@article {pmid41909522,
year = {2026},
author = {Salini Jancy Rani, A and Balamurugan, BJ},
title = {Novel Roman domination-based graph energies for QSPR analysis of neuroprotective herbal compounds in Alzheimer's disease treatment.},
journal = {Frontiers in chemistry},
volume = {14},
number = {},
pages = {1731656},
pmid = {41909522},
issn = {2296-2646},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which U.S. Food and Drug Administration (FDA)-approved drugs provide only temporary symptomatic relief and often cause adverse effects. Plant-derived bioactive phytochemicals are emerging as promising alternatives due to their multi-targeted neuroprotective properties and reduced toxicity. In this article, herbal anti-Alzheimer's compounds are analyzed using a novel graph molecular modeling. In chemical graph theory, molecular structures are represented as isomorphic molecular graphs G V , E , where V and E denote the set of vertices (atoms) and edges (chemical bonds) respectively. Classical graph matrices such as adjacency and Laplacian matrices capture the molecular connectivity but fail to account for hierarchical differences in atomic influence. To address this limitation, Roman domination is employed to represent the hierarchical dominance of atoms within molecular structures. A Roman domination function (RDF) on a graph G V , E is a mapping f : V → 0 , 1 , 2 such that every atom v with f v = 0 has at least one adjacent atom u with f u = 2 , reflecting the hierarchical dominance within the isomorphic molecular graph. Based on this principle, the Roman domination-based matrices and corresponding graph energies are introduced in this article. Quantitative Structure-Property Relationship (QSPR) graph models are developed using the Roman energies through linear, quadratic and cubic regression analysis. The results demonstrate superior performance compared to classical approaches, with the quadratic regression showing the strongest correlations and lowest standard error. Internal validation through the Y-randomization and Leave-One-Out Cross-Validation methods confirmed the stability of the models, while external validation on the herbal compound Kaempferol (r = 0.993) further supported their predictive reliability. These findings underscore the robustness of Roman energies, establishing them as powerful molecular descriptors that offer enhanced accuracy in the QSPR analysis and hold promise for applications in drug design, materials informatics and computational chemistry.},
}

@article {pmid41909700,
year = {2026},
author = {Yu, J and Tang, B and Gu, Z and Wang, G and Liu, A},
title = {Organoid-microglia system for modeling the immune microenvironment of the brain and retina.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1747589},
pmid = {41909700},
issn = {1664-3224},
mesh = {Humans ; *Organoids/immunology/cytology ; *Microglia/immunology/metabolism ; *Retina/immunology/cytology ; Animals ; *Brain/immunology/cytology ; *Cellular Microenvironment/immunology ; },
abstract = {Glial cells play a critical role in neural development, function, and immune regulation, with microglia serving as the principal immune cells of the central nervous system and retina. Although microglia are central to neuroinflammation and disease progression, progress in understanding human microglial biology has been limited by the lack of physiologically relevant in vitro models. Stem cell-derived brain and retinal organoids provide three-dimensional systems that recapitulate human tissue architecture and developmental trajectories, offering new opportunities to study neuroimmune interactions. This review summarizes strategies for integrating microglia into neural organoids through co-differentiation and transplantation, and outlines methodologies for establishing humanized immune microenvironments and assessing microglial maturation, migration, phagocytic function, and inflammatory activation. We highlight applications of organoid-microglia models in neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder, Alzheimer's disease, and retinal diseases, as well as their potential in drug screening and microglia-targeted interventions. Additionally, emerging technologies-such as organ-on-a-chip platforms, spatial transcriptomics, and multi-omics analyses-are enhancing the physiological relevance and analytical power of these systems. Overall, organoid-microglia platforms bridge a critical gap between conventional cell culture and in vivo models, enabling deeper insights into neuroimmune interactions and accelerating the development of precise immunomodulatory therapies.},
}

Humans
*Organoids/immunology/cytology
*Microglia/immunology/metabolism
*Retina/immunology/cytology
Animals
*Brain/immunology/cytology
*Cellular Microenvironment/immunology

@article {pmid41909894,
year = {2025},
author = {Hensen, T and Ahmad, S and Kastenmüller, G and Kraaij, R and Ghanbari, M and Ikram, A and Kaddurah-Daouk, R and Thiele, I},
title = {In silico metabolic modelling links microbiome-derived metabolites to risk factors of Alzheimer's disease.},
journal = {Gut microbes reports},
volume = {2},
number = {1},
pages = {2443171},
pmid = {41909894},
issn = {2993-3935},
abstract = {The gut microbiome has become increasingly recognized for its role in the pathogenesis of Alzheimer's disease (AD) and is thought to influence AD pathogenesis via metabolic crosstalk with the host. However, mechanistic pathways connecting the gut microbiome to AD pathogenesis remain unknown. To explore potential mechanistic pathways in AD pathogenesis, we created host-microbiome whole-body metabolic models personalized with 16S rRNA microbiome data and predicted emergent metabolic contributions of gut microbiomes. We analyzed 63 metabolites in blood with previously known links with AD. These in silico predictions were then associated with major risk factors for AD in a cohort of 1,065 aging non-AD individuals and subsequently used to inform targeted analyses on serum metabolomics. Our analysis identified increased host-microbial production of L-arginine in older individuals. Lower production of deoxycholate correlated with the neuroprotective APOE E2 allele and it decreased with higher global cognition. Serum metabolomics from the same individuals of cholesterol products and bile acid metabolism corroborated the modeling predictions, suggesting a potential link between the APOE genotype and cognitive health. In conclusion, this study associated metabolic gut microbiome influences on human metabolism with risk factors for AD and identified cholesterol and bile acid metabolism to potentially link with AD pathogenesis.},
}

@article {pmid41909980,
year = {2026},
author = {Loukola, HR and Kärkkäinen, M and Selander, T and Honkalampi, K and Koivisto, AM and Saari, TT},
title = {Associations between apathy and global cognition in a 5-year follow-up of individuals with Alzheimer's disease.},
journal = {Journal of neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jnp.70044},
pmid = {41909980},
issn = {1748-6653},
support = {//Kuopion Yliopistollinen Sairaala/ ; //Päivikki ja Sakari Sohlbergin Säätiö/ ; },
abstract = {Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) associated with cognitive and functional impairment. Longitudinal studies have examined the associations between apathy and cognition in AD and other dementias, but more information is needed to understand whether the relationships are consistent longitudinally, and whether apathy relates to decline in AD-related cognitive domains or to drop-out rates in the follow-up. We used data from 236 people (age M = 75.15 and 51.3% female at baseline) with very mild or mild AD from the Finnish ALSOVA study with up to 5 years of follow-up. Global cognition was measured with the Consortium to Establish a Registry for Alzheimer's disease-Neuropsychological Battery, apathy with the Neuropsychiatric Inventory, and disease severity with the Clinical Dementia Rating-Sum of Boxes. Associations between cognition and apathy were examined with correlation analyses, linear regression analyses and linear mixed models. In longitudinal analyses, we found that apathy was associated with worse global cognition (B = -0.39, SE = 0.12, p = .001) after adjusting for disease severity. However, apathy and global cognition were not consistently associated with one another in cross-sectional analyses. Older age (OR = 0.95, p = .02), but not apathy, was associated with a lower likelihood of participating in the final follow-up visit. In conclusion, apathy associates with worse global cognition longitudinally, but when examined cross-sectionally, the apathy-cognition associations are inconsistent. Apathy at baseline does not seem to affect drop-out rates in a long follow-up of individuals with very mild or mild AD.},
}

@article {pmid41910174,
year = {2026},
author = {Öhman, F and Raket, LL and Schöll, M and , },
title = {Cognitive Trajectories from Preclinical Alzheimer's Disease to Dementia.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e18124},
doi = {10.1002/advs.202518124},
pmid = {41910174},
issn = {2198-3844},
support = {KAW2014.0363//Knut and Alice Wallenberg Foundation/ ; KAW2023.0371//Knut and Alice Wallenberg Foundation/ ; 2017-02869//Swedish Research Council/ ; 2021-02678//Swedish Research Council/ ; 2021-06545//Swedish Research Council/ ; 2023-06188//Swedish Research Council/ ; 101132933//European Union's Horizon Europe research and innovation program/ ; 101112145//European Union's Horizon Europe research and innovation program/ ; R01 AG081394-01/NH/NIH HHS/United States ; RS-2023-00263612//National Research Foundation of Korea/ ; ALFGBG-813971//Swedish state, the Swedish government and the County Councils, the ALF-agreement/ ; ALFGBG-965326//Swedish state, the Swedish government and the County Councils, the ALF-agreement/ ; FO2021-0311//Swedish Brain Foundation/ ; FO2024-0372//Swedish Brain Foundation/ ; AF-994900//Swedish Alzheimer Foundation/ ; //Sahlgrenska Academy at the University of Gothenburg/ ; VGFOUREG-995510//Västra Götaland Region R&D/ ; //Gates Ventures/ ; },
abstract = {Alzheimer's disease (AD) is marked by progressive cognitive decline, highlighting the importance of cognitive assessment in both clinical practice and research. This study investigates the temporal dynamics of cognitive decline and the differential sensitivity of cognitive measures across the AD spectrum. Cognitive measures, functional assessments, and amyloid-beta (Aβ) and tau positron emission tomography (PET) scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) are analyzed using a latent-time disease progression model. Data from 1,447 participants across cognitively normal, mild cognitive impairment, and dementia stages are positioned along an estimated AD timeline. The model estimates a ∼20-year progression from initial Aβ PET positivity to late-stage dementia. Cognitive trajectories reveal that cognitive measures deviate at different time points, with varying levels of abnormality across the disease continuum. These findings demonstrate that cognitive measures differ markedly in their sensitivity across the AD continuum. Characterizing when specific measures become abnormal provides a framework for stage-appropriate test selection in clinical practice, improving clinical interpretation while informing the choice of cognitive endpoints and inclusion criteria in clinical trials.},
}

@article {pmid41910248,
year = {2026},
author = {Kwetsie, H and Verberk, IMW and van Ool, JS and Rampen, AJJ and Rousset, RZ and Wolf, NI and Maes-Festen, DAM and van Karnebeek, CDM and Teunissen, CE and Boot, E and van Eeghen, AM},
title = {Serum NfL, GFAP, and p-tau217 in adults with drug-resistant epilepsy and intellectual disabilities: Signs of ongoing neural injury.},
journal = {Epilepsia},
volume = {},
number = {},
pages = {},
doi = {10.1002/epi.70218},
pmid = {41910248},
issn = {1528-1167},
support = {//'s Heeren Loo/ ; //EpilepsieNL/ ; },
abstract = {OBJECTIVE: Adults with epilepsy and intellectual disabilities (IDs) may be at increased risk of dementia, but clinical evaluation is complex and use of conventional biomarkers is often considered too invasive. We explored abnormality of serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau-217 (p-tau217) in these adults, and their associations with clinical outcomes.

METHODS: Serum biomarker levels were quantified with Single Molecule Array (Simoa) in 68 adults with co-occurring epilepsy and ID at a median age of 52.0 (range 24-76) years. Levels were classified normal/abnormal (>95th percentile) in comparison to reference data of age-matched healthy controls (NfL, GFAP) or Alzheimer's disease (AD)-specific cutoff (p-tau217). Associations with age were assessed with correlations and segmented regression analyses. Associations with adaptive decline, suspected dementia, ID, epilepsy, antiseizure medication, comorbidity, and mortality were explored using chi-square tests, Mann-Whitney U tests, log rank tests, and Cox regression analyses.

RESULTS: NfL levels were abnormal in 51.5%, GFAP in 63.2%, and p-tau217 in 2.9%. Age-corrected Z-scores of NfL were still significantly associated with age (r = .31, p = .01). Elevated NfL was associated with significant adaptive decline (χ[2] = 7.20, p = .007), suspected dementia (χ[2] = 10.73, p = .001), monthly seizure frequency (χ[2] = 5.21, p = .03), non-early seizure onset (U = 281, p < .001), carbamazepine use (χ[2] = 4.38, p = .04), and mortality (Log rank p = .04; hazard ratio [HR] p = .007). GFAP levels were significantly higher in severe ID (median Z = 2.5) compared to mild ID (median Z = 1.6) (U = 196, p = .02). Having abnormal levels of GFAP and NfL simultaneously was the most common biomarker profile in participants with suspected dementia (69.2%).

SIGNIFICANCE: NfL and GFAP were abnormal in many participants, coinciding with clinical decline. Findings are suggestive for ongoing neural injury, but not necessarily for AD.},
}

@article {pmid41910400,
year = {2026},
author = {Ma, L and Zheng, Y and Huang, J and Yang, X},
title = {Length-Dependent Aβ-Gelsolin Interactions Regulate Amyloid Aggregation in Alzheimer's Disease.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c06477},
pmid = {41910400},
issn = {1520-6882},
abstract = {The pathological involvement of β-amyloid (Aβ) protein variants in Alzheimer's disease (AD) progression manifests through distinct aggregation patterns, neurotoxic profiles, and spatial distributions contingent upon their polypeptide lengths. While gelsolin (GSN) has emerged as a potential regulatory factor in Aβ dynamics, the structural determinants governing its interaction with various Aβ isoforms remain poorly characterized. Building upon our previous demonstration of GSN-mediated inhibition of β-amyloid protein 1-42 (Aβ1-42) fibrillogenesis through monomer binding, we present the first systematic investigation of GSN interaction dynamics with Aβ fragments of varying lengths (Aβ1-42, Aβ1-40, Aβ9-37, Aβ1-16, and Aβ1-11) using dual polarization interferometry. Our experimental paradigm employed simultaneous real-time monitoring of three critical biophysical parameters (adsorbed mass, layer thickness, and density) for characterizing binding kinetics and conformational changes. This multiparametric analysis revealed a pronounced length-dependent mechanism underlying GSN-Aβ interactions. Through an integrated approach combining multiscale experimental dynamics with computational docking simulations, we elucidated the intricate relationship between interaction thermodynamics and structural complementarity. These findings established a theoretical framework for developing stage-specific therapeutic interventions in AD management while advancing our understanding of molecular determinants in protein chaperone systems.},
}

@article {pmid41910452,
year = {2026},
author = {He, N and Wu, H and An, N and Bu, J and Li, Y and Dai, Y and Ou, Y and He, F},
title = {Polygenic and polysocial risk scores in post-type 2 diabetes dementia: Risk stratification and predictive modeling in the UK Biobank cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435200},
doi = {10.1177/13872877261435200},
pmid = {41910452},
issn = {1875-8908},
abstract = {BackgroundDementia is a common complication of type 2 diabetes mellitus (T2DM), influenced by both genetic susceptibility and social disadvantages. While polygenic risk scores (PRS) have been widely applied to assess genetic vulnerability, the contribution of social determinants and their interaction with genetic risk are less understood.ObjectiveThis study aimed to investigate the independent and joint effects of PRS and polysocial risk scores (PsRS) on post-T2DM dementia risk.MethodsA prospective cohort study was conducted using UK Biobank data. PsRS and PRS were derived from multidimensional social and genetic indicators, respectively. Cox proportional hazards models were used to examine their associations with dementia outcomes. In genetically susceptible individuals, seven machine learning models were applied to predict dementia risk. SHAP and ALE were used to interpret feature importance.ResultsAmong 5,624 participants with T2DM, those in the highest PsRS group had a markedly elevated risk of all-cause dementia (HR = 2.738; 95% CI: 1.556-4.818, p < 0.001). This association persisted among genetically susceptible individuals. Machine learning analyses in the medium-to-high PRS group showed that eXtreme Gradient Boosting (XGBoost) achieved the best predictive performance (F1 = 0.735, AUC = 0.726). SHAP interpretation highlighted employment status (mean |SHAP value| = 0.45) and educational level (mean |SHAP value| = 0.19) as the strongest social contributors to dementia risk.ConclusionsBoth social disadvantages and genetic susceptibility contribute to dementia risk in individuals with T2DM. These findings underscore the importance of addressing modifiable social factors in targeted dementia prevention strategies for high-genetic-risk populations.},
}

@article {pmid41910458,
year = {2026},
author = {Levine, DA and Hayward, RA and Sussman, JB and Whitney, RT and Gałecki, AT and Briceño, EM and Gross, AL and Giordani, BJ and Elkind, MSV and Gaskin, DJ and Gottesman, RF and Sidney, S and Yaffe, K and Burke, JF},
title = {Alternative clinical trial designs to find a clinically important effect size of blood pressure-lowering on cognitive impairment and dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430953},
doi = {10.1177/13872877261430953},
pmid = {41910458},
issn = {1875-8908},
abstract = {BackgroundBlood pressure (BP) lowering might reduce the risk of cognitive impairment and dementia (CID), but more information is needed to design trials optimally.ObjectiveTo estimate trial sample sizes and durations for detecting BP-lowering effects on CID.MethodsWe estimated trial sample sizes and durations for finding an effect of a Systolic Blood PRessure INtervention Trial (SPRINT)-based BP-lowering strategy versus usual care on CID and global cognition using our MIchigan ChROnic Disease SIMulation Model (MICROSIM), which simulated adults with the US population's demographics and vascular risk factors and assumed BP-lowering's effect on CID and global cognition from our pooled cardiovascular cohort study.ResultsOver >139 million simulated trials across 78,000 parameters, the SPRINT-based BP-lowering strategy (versus usual care) resulted in a 2% CID relative risk reduction (RRR), much smaller than the CID RRR (15%) found in SPRINT Memory and Cognition IN Decreased Hypertension (MIND). Detecting a 2% CID RRR with >80% power would require 10-year trials with samples >50,000. Identifying the BP-lowering strategy's effect on mean global cognition would require trials of ≥10 years with >30,000 participants. However, trials of 5 years with 10,000 participants would have the power to detect the strategy's effect assuming a 15% CID RRR in SPRINT MIND.ConclusionsIn this microsimulation study, we found that trials would need to be large with long follow-ups to identify the causal effects of BP-lowering on CID and cognition. However, assuming the 15% CID RRR in SPRINT MIND, trials with more feasible sizes and durations could detect those effects.},
}

@article {pmid41910460,
year = {2026},
author = {Wang, X and Zhang, C and Liu, X and Tai, Y and Ma, G and Kong, M and Ba, M and , },
title = {Effects of APOE ε4 and amyloid pathology on longitudinal tau biomarkers, neurodegeneration, and cognitive decline in mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435429},
doi = {10.1177/13872877261435429},
pmid = {41910460},
issn = {1875-8908},
abstract = {BackgroundMild cognitive impairment (MCI) confers an increased risk of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for late-onset AD and is strongly associated with amyloid-β (Aβ) pathology. However, whether Aβ burden is associated with APOE ε4-related longitudinal changes in tau pathology, neurodegeneration, and cognitive decline in MCI remains incompletely understood.ObjectiveTo examine whether Aβ burden is associated with APOE ε4-related longitudinal changes in tau pathology, neurodegeneration, and cognition in MCI using ε4 carrier-based and genotype-stratified approaches.MethodsData from 396 individuals with MCI in the Alzheimer's Disease Neuroimaging Initiative were analyzed. Longitudinal changes in cerebrospinal fluid (CSF) tau biomarkers, neurodegeneration, and cognition were quantified using individual-specific slopes and examined in multiple linear regression models in relation to APOE ε4 carrier status and Aβ burden. Mediation analyses were used to quantify the associations between baseline Aβ burden and APOE ε4-related longitudinal changes across ε4 carrier-based and genotype-stratified analyses.ResultsAPOE ε4 carriers showed greater longitudinal increases in CSF tau and more pronounced declines in glucose metabolism, regional brain volumes, and cognition. Baseline Aβ burden showed associations with APOE ε4-related longitudinal changes in CSF tau, cerebral glucose metabolism, brain atrophy, and memory and global cognition. A similar pattern was also observed in genotype-stratified analyses.ConclusionsThese longitudinal findings suggest that Aβ burden is closely associated with APOE ε4-related tau accumulation, neurodegeneration, and cognitive decline in individuals with MCI.},
}

@article {pmid41910461,
year = {2026},
author = {Kong, X and Han, R and Fan, X and Wei, K and Ma, Z and Yang, G and Zhao, Y and Yang, Y and Yang, Y and Hong, J and Liu, J and Zhang, D and Ma, X},
title = {Acupuncture as an adjunct therapy for mild Alzheimer's disease: A randomized clinical trial.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435880},
doi = {10.1177/13872877261435880},
pmid = {41910461},
issn = {1875-8908},
abstract = {BackgroundPreclinical studies suggest acupuncture may offer symptomatic relief or modify disease progression in Alzheimer's disease (AD), yet clinical evidence remains limited.ObjectiveThis study evaluated whether adding acupuncture to cholinesterase inhibitors improves outcomes in patients with mild AD and whether any benefits persist after treatment ends.MethodsIn this randomized, single-blind trial, participants with mild AD received either active or sham acupuncture three times per week for 14 weeks in addition to ongoing donepezil therapy, followed by a 14-week washout phase during which acupuncture was discontinued while donepezil was maintained. The primary outcome was change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog12) from baseline.ResultsA total of 160 participants were enrolled, and 157 were included in the primary analysis (78 active, 79 sham). At week 14, the mean change in ADAS-cog12 was -1.20 for the active acupuncture group versus 0.36 for the sham acupuncture group, yielding a difference of -1.50 (p < 0.001). After washout, no significant difference remained (difference, -0.31; p = 0.54). Adverse events occurred in 37.2% of the active and 45.6% of the sham group. Donepezil-related adverse events were less frequent with active acupuncture (6.4% versus 16.5%; p < 0.05).ConclusionsAcupuncture, when added to donepezil, improved cognition during active treatment and was associated with fewer cholinergic side effects in patients with mild AD. The cognitive benefits did not persist after acupuncture was discontinued, suggesting that acupuncture serves as an adjunctive symptomatic therapy rather than a disease-modifying intervention.Trial registrationClinicalTrials.gov [NCT05078944].},
}

@article {pmid41910462,
year = {2026},
author = {Chi, L and Qiao, M and Huang, A and Chen, S and Yang, X and Wu, H and Lin, X and Chen, J and , },
title = {Longitudinal trajectories of amyloid-β-driven alterations in voxel-mirrored homotopic connectivity and cognitive decline in mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436704},
doi = {10.1177/13872877261436704},
pmid = {41910462},
issn = {1875-8908},
abstract = {BackgroundAmyloid-β (Aβ) deposition in mild cognitive impairment (MCI) disrupts interhemispheric homotopic connectivity, yet its longitudinal course is unclear.ObjectiveWe aim to characterize the longitudinal decay of voxel-mirrored homotopic connectivity (VMHC) in MCI patients, elucidate underlying Aβ-associated mechanisms, and link these processes to cognitive decline.MethodsEighty-three ADNI participants (60 MCI, 23 cognitively normal [CN]) underwent baseline and two-year follow-up. MCI cases were stratified by [18]F-AV45 PET into Aβ-positive (MCI-Aβ+, n = 44) and Aβ-negative (MCI-Aβ-, n = 16) subgroups. VMHC and corpus-callosum volume were compared across groups (ANOVA). Spearman correlations linked regional VMHC to cognition, cerebrospinal fluid (CSF) biomarkers, and callosal volume. Linear mixed-effects models tested group-by-time interactions; two-year VMHC change was related to parallel cognitive decline.ResultsAt baseline, MCI-Aβ- patients showed lower VMHC in the fusiform and postcentral gyri, whereas MCI-Aβ+ patients exhibited additional reductions in the precuneus, superior frontal gyrus, cerebellum, and superior occipital gyrus. Lower VMHC correlated with poorer cognition, corpus-callosum atrophy, and abnormal CSF profiles; callosal volume itself did not differ between groups. Longitudinally, MCI-Aβ+ participants exhibited a slower VMHC decline across the posterior cingulate, cerebellum and thalamus. Two-year cumulative change in VMHC inversely correlated with change in cognitive performance.ConclusionsAβ burden shapes distinct trajectories of interhemispheric connectivity loss in MCI. VMHC decline tracks multi-domain cognitive deterioration and may serve as a biomarker of progression toward Alzheimer's disease.},
}

@article {pmid41910470,
year = {2026},
author = {Ye, X and Hu, K and Liu, R},
title = {Aerobic exercise intervention in Alzheimer's disease: Proteomic insights into peripheral T cell-mediated immune pathways.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436840},
doi = {10.1177/13872877261436840},
pmid = {41910470},
issn = {1875-8908},
abstract = {BackgroundPhysical exercise shows neuroprotective and anti-inflammatory effects in Alzheimer's disease (AD) models, but whether it modulates neuroinflammation through regulation of peripheral T-cell activity is still unresolved.ObjectiveThe present study aimed to explore the mechanisms by which aerobic exercise regulates peripheral T cell-mediated immune responses and their potential contribution to neuroinflammation in AD.MethodsMale wild-type mice and APP/PS1 transgenic mice were divided into four groups: wild-type sedentary mice (WT-SE) group, wild-type exercise group (WT-EX), APP/PS1 transgenic AD sedentary mice (AD-SE) group, and APP/PS1 transgenic AD exercise mice (AD-EX) group. The sedentary groups received no exercise training, while the exercise groups underwent a 3-month treadmill aerobic exercise intervention. At the end of the intervention, T lymphocytes were isolated from spleens. Label-free proteomics combined with LC-MS/MS was used to identify differentially expressed proteins (DEPs) and perform functional and pathway enrichment analyses. Differentially expressed protein-coding genes were validated at the mRNA level using RT-qPCR.ResultsA total of 3399 proteins were quantified across the four groups. Applying a threshold of |log2 fold change| > 0.67 and q-value < 0.05, 913 DEPs were identified. These DEPs were significantly enriched in biological processes including immune system processes, protein-containing complexes, and structural molecule activity, as well as signaling pathways including AD, TGF-β, and apoptosis.ConclusionsOverall, HSP90AB1, HSP90AA1, BAG5, DNAJC8, CTSD, and ANXA1 may play a role in peripheral T-cell immune dysregulation in AD, with potential implications for central neuroinflammation. Furthermore, the beneficial effects of aerobic exercise on AD-related peripheral immune alterations, and its potential modulation of neuroinflammation, may be associated with expression changes in DEPs including Ppp2r1b, Pde2a, Casp8, Apaf-1, Dnajb11, and Dnajc13.},
}

@article {pmid41910471,
year = {2026},
author = {Shah, J and Karanja, W and Merali, Z and Ali, SK and Kalaria, RN},
title = {Trends and projections for Alzheimer's disease and other dementias in Kenya: Analysis of the global burden of disease data 1990-2021 in relation to Africa and the world.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261434256},
doi = {10.1177/13872877261434256},
pmid = {41910471},
issn = {1875-8908},
abstract = {BackgroundDementia, predominantly Alzheimer's disease, poses a growing public health challenge in low- and middle-income countries like Kenya. This is driven by rapid population aging and rising prevalence of non-communicable diseases. Understanding trends in dementia burden is essential for informing healthcare planning and preventive strategies.ObjectiveThis study aimed to analyze trends in dementia burden in Kenya from 1990 to 2021 using the Global Burden of Disease (GBD) data, comparing estimates with sub-Saharan Africa, Africa, and global benchmarks, while assessing modifiable risk factors and projecting to 2050.MethodsSecondary analysis of GBD 2021 data examined age-standardized incidence, prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) for Alzheimer's disease and other dementias in Kenya, disaggregated by age and sex. Joinpoint regression calculated average annual percent changes (AAPC); autoregressive integrated moving average (ARIMA) models forecasted prevalence, mortality, and DALYs to 2050.ResultsIn 2021, Kenya's age-standardized prevalence rate (ASPR) was 605.1 per 100,000 (95% UI: 525.2-689.5), exceeding SSA (529.5) and Africa (590.0) but below global (694.0); incidence was 105.1 (95% UI: 91.6-119.6). Females bore higher burdens across metrics (e.g., ASPR: 697.1 vs. 459.4 in males). From 1990-2021, ASPR and incidence declined (AAPC: -0.14% to -0.21%, p < 0.001), while DALYs (AAPC: 0.19%-0.23%, p < 0.001) and mortality (AAPC: 0.29%-0.36%, p < 0.001) rose, driven by YLLs.ConclusionsDespite declining age-standardized incidence and prevalence, rising mortality and DALYs signal escalating dementia burden in Kenya, amplified by metabolic risks and aging. Females face disproportionate impacts. Urgent integration of risk reduction into primary care, enhanced surveillance, and culturally tailored strategies per the Nairobi Declaration are needed to mitigate future challenges in low- and middle-income countries.},
}

@article {pmid41910476,
year = {2026},
author = {Baak, BN and de Boer, C and Nooralishahi, M and Adolfsen, PEA and Lemmens, L and van Harten, AC and Vijverberg, EGB and van der Flier, WM and Herings, RMC},
title = {The ABOARD-RWD infrastructure: Using linked real-world data to study the diagnosis and management of dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261429858},
doi = {10.1177/13872877261429858},
pmid = {41910476},
issn = {1875-8908},
abstract = {BackgroundResearch into Alzheimer's disease has primarily focused on clinical cohorts, yet many patients are diagnosed and followed in primary care. An infrastructure comprising routinely collected and linked electronic health records from primary care, hospitals, and pharmacies, i.e., real-world data (RWD), can provide insight into disease trajectories.ObjectiveWe aim to describe the ABOARD-RWD infrastructure, focusing on its design, data sources, representativeness, and potential applications.MethodsThe ABOARD-RWD infrastructure includes 79,114 Dutch adults with incident dementia (2011-2022), identified through dementia diagnoses, free-text mentions, or use of dementia-related drugs. Linked data includes general practitioner (GP), hospital care, outpatient pharmacy, laboratories, and specialized registries. Descriptive analyses assessed demographics, prevalence, and clinical characteristics.ResultsThe ABOARD-RWD Infrastructure (age 81 ± 9, 59% female) has a median 8.6-year look-back period (IQR 4.7-12.3) and 2.2-year follow-up (IQR 0.9-4.2) from first dementia diagnosis. Dementia was recorded in GP for 86%, hospitals for 34%, and 22% received dementia-related drugs. Dementia prevalence in 2022 was 9.3 per 1,000 (10.9 women, 7.6 men), aligning with national estimates. Mini-Mental State Examinations were recorded for 62%: 35% scored ≥24, 26% scored 18-23, 13% scored <18, and 25% had an unknown score. Cardiovascular disease was recorded in 48%, hypertension in 51%, diabetes in 23%, hypercholesterolemia in 19%, cerebrovascular disease in 20%, asthma/chronic obstructive pulmonary disease in 14%, psychiatric conditions in 17%, and sleep disturbances in 13%.ConclusionsThe ABOARD-RWD Infrastructure enables real-world, longitudinal dementia research across multiple healthcare settings. It captures representative patient journeys, supporting studies on risk factors, diagnosis, management, and outcomes.},
}

@article {pmid41910477,
year = {2026},
author = {Querry, M and Botzung, A and Mérignac, J and Demuynck, C and Gommel, G and Muller, C and Philippi, N and Ravier, A and Sanna, L and Blanc, F},
title = {What about emotions in prodromal and mild dementia with Lewy bodies? A behavioral study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435989},
doi = {10.1177/13872877261435989},
pmid = {41910477},
issn = {1875-8908},
abstract = {BackgroundA growing body of literature has documented emotional disorders in patients with dementia with Lewy bodies (DLB). While emotional symptoms have been well studied in Alzheimer's disease (AD) and Parkinson's disease (PD), no study to date has provided a comprehensive overview of emotional disturbances specifically associated with DLB.ObjectiveThis study aimed to investigate the emotional profile of patients with prodromal or mild DLB compared to healthy controls.MethodsBehavioral data were collected from 24 prodromal or mild DLB patients, and 24 healthy participants, matched for age, gender and educational level. Statistics, including group comparisons and correlation analyses, were conducted using the following measures: the Florida Affect Battery (FAB), the 20-item Toronto Alexithymia Scale (TAS-20), the Echelle d'Humeur Depressive (EHD), and the Generalized Anxiety Disorder 7-item (GAD-7) scale.ResultsPatients with DLB demonstrated significantly impaired performance on the FAB alongside elevated scores on the TAS-20, the EHD, and the GAD-7 compared to controls.ConclusionsThese findings highlight profound disruptions in internal emotional experience among patients with prodromal or mild DLB, notably marked by elevated alexithymic traits, altered emotional expression, emotional dyscontrol, anxiety, and impairments in automatic and implicit recognition of facial emotions. Our study supports the critical need for early detection, systematic evaluation, and personalized management of emotional symptoms through targeted interventions.},
}

@article {pmid41910496,
year = {2026},
author = {Jiang, Y and Zhu, X and Zhao, L and Du, Y and Wang, H and Fan, H and Ma, K and Lu, H and Ma, D and Qiu, J and Zhang, G},
title = {The atherogenic index of plasma and triglyceride glucose-body mass index are inversely associated with cognitive impairment in middle-aged and older Chinese adults: A community-based cohort study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261434985},
doi = {10.1177/13872877261434985},
pmid = {41910496},
issn = {1875-8908},
abstract = {BackgroundAlthough metabolic disorders are associated with cognitive dysfunction, the relationship with composite metabolic indices remains unclear.ObjectiveThis study aimed to examine the longitudinal associations of the atherogenic index of plasma (AIP) and the triglyceride-glucose body mass index (TyG-BMI) with incident cognitive impairment in a community-based cohort of middle-aged and older adults.MethodsThis prospective cohort study included 1492 cognitively normal adults (age ≥40 years). Baseline AIP and TyG-BMI were calculated from blood samples. Incident cognitive impairment was defined using education-specific Mini-Mental State Examination cut-offs at a 2-year follow-up. Associations were evaluated using multivariable logistic regression (adjusted for age, sex, education, apolipoprotein E ε4, and other confounders) and restricted cubic spline models.ResultsAmong participants, 59.4% were female, with a median age of 55 years (IQR, 48-63). Over a median follow-up of 2.02 years (IQR, 1.98-2.06), 133 participants (8.9%) developed cognitive impairment. After full adjustment, higher levels of AIP (OR = 0.21, 95% CI: 0.09-0.50) and TyG-BMI (OR = 0.99, 95% CI: 0.98-0.99) were inversely associated with the risk of cognitive impairment (both p < 0.001). A dose-response relationship was observed, with risk decreasing as index levels increased.ConclusionsIn this middle-aged and older Chinese cohort, higher AIP and TyG-BMI were associated with a reduced short-term risk of cognitive impairment. These findings highlight the complex, context-dependent nature of metabolic-cognitive associations, suggesting these indices may reflect a metabolic profile relevant to early cognitive maintenance.},
}

@article {pmid41910642,
year = {2026},
author = {Thorns, V and Mallory, M and Hansen, L and Masliah, E},
title = {Correction: Alterations in glutamate receptor 2/3 subunits and amyloid precursor protein expression during the course of Alzheimer's disease and Lewy body variant.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
doi = {10.1007/s00401-026-02997-5},
pmid = {41910642},
issn = {1432-0533},
}

@article {pmid41910646,
year = {2026},
author = {Sugiyama, K and Horvat, A and Dolinar, K and Pirkmajer, S and Furlani, B and Jorgačevski, J and Vardjan, N and Zorec, R},
title = {Dopamine-Induced L-Lactate Production in Cortical Astrocytes Cross-Reacts with β1-Adrenoceptor-Mediated cAMP Signalling.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1442},
pmid = {41910646},
issn = {2152-5250},
abstract = {Astrocytes maintain homeostasis of the central nervous system and supply neurons with metabolic substrates essential for synaptic plasticity and learning. Upon stimulation by noradrenaline (NA), released primarily by locus coeruleus (LC) neurons and acting via volume transmission, astrocytes enhance aerobic glycolysis and produce L-lactate, a process critical for energy support yet dependent on β-adrenoceptor-mediated cyclic adenosine monophosphate (cAMP) signalling. In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, early degeneration of the LC diminishes noradrenergic tone, potentially impairing astrocyte metabolic function. Dopamine (DA), acting via volume transmission like NA, released from the substantia nigra pars compacta, may also modulate astrocytic metabolism; however, this has not yet been investigated at the cellular level. Using fluorescence resonance energy transfer-based nanosensor imaging in cultured rat cortical astrocytes, we investigated DA-induced cAMP signalling and L-lactate production. DA elicited a dose-dependent increase in cytosolic cAMP (EC50 = 1.25 μM) and stimulated delayed L-lactate production in a receptor-mediated, cAMP-dependent manner. Knockdown of β1-adrenoceptors (Adrb1) significantly reduced these effects. At the same time, super-resolution stimulated emission depletion microscopy revealed minimal nanoscale colocalization between D1 and β1 receptors, suggesting that at least at higher DA concentrations, β1-adrenoceptors contribute to DA-mediated metabolic regulation. These findings identify a novel dopaminergic pathway for astrocytic glycolytic activation, informing future studies examining dysregulation of monoaminergic-astrocytic signalling in neurodegenerative diseases.},
}

@article {pmid41910650,
year = {2026},
author = {Aamir, SW and Huang, JW and Qadeer, A and Alzahrani, KJ and Alsharif, KF and Alzahrani, FM and Zaheen, S and Abuderman, A and Chen, CC and Hussain, S},
title = {Extracellular Vesicles as Key SASP Carriers Driving Cellular Senescence, Inflammaging, and Therapeutic Opportunities in Aging and Age-Related Diseases.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0134},
pmid = {41910650},
issn = {2152-5250},
abstract = {The progressive decline in physiological processes with aging is a complex biological process that increases susceptibility to age-related diseases. Cellular senescence is a primary contributor to this process, a state of sustained cell cycle arrest accompanied by a distinctive secretory profile known as the Senescence-Associated Secretory Phenotype (SASP). In recent years, extracellular vesicles (EVs), including exosomes and microvesicles (MVs), have emerged as key mediators of intercellular communication by carrying bioactive molecules, such as proteins, lipids, and nucleic acids. In this review, we describe how EVs are important SASP vectors that transmit senescent signals to nearby cells, driving immunosenescence, persistent inflammation (inflammaging), and other aging characteristics, such as stem cell exhaustion and genomic instability. Furthermore, we highlight the dual function of EVs as both pathogenic drivers of aging-related dysfunctions and promising therapeutic agents. In addition, we emphasize their potential as diagnostic biomarkers for age-related diseases, including cardiovascular disease, osteoporosis, and Alzheimer's disease. Finally, we explore the emerging therapeutic uses of EVs, particularly those derived from mesenchymal stem cells (MSCs), to promote tissue repair, reduce aging phenotypes, and serve as engineered drug-delivery systems. This study highlights the critical role of EVs in aging mechanisms and establishes them as potent diagnostic and therapeutic tools for anti-aging.},
}

@article {pmid41910654,
year = {2026},
author = {Yu, Z and Li, H and Wang, Y and Li, Y and Shen, F and Wang, Y},
title = {The Microglial Lactate-Lactylation Axis as a Metabolic-Epigenetic Driver of Alzheimer's Disease.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1487},
pmid = {41910654},
issn = {2152-5250},
abstract = {The idea of amyloid-β (Aβ) plaques and tau neurofibrillary tangles has long been central to framing an understanding of Alzheimer disease (AD), but emerging and growing evidence now points to bioenergetic failure and metabolic-epigenetic crosstalk as central to AD progression. Hai et al. summarize animal and human biofluid and neuroimaging data to carve out the pathophysiology of AD in relation to the role of disrupted glucose metabolism, lactate build-up and protein lactylation in glucose metabolism, in their comprehensive review "Lactate, Lactylation and Alzheimer Disease". Building on Hai et al.'s key contributions, we offer a complementary perspective. The microglial lactate-lactylation axis may be remodeled across disease stages during chronic neuroinflammation, potentially serving compensatory functions early but shifting toward maladaptive, pro-inflammatory amplification at later stages. In light of emerging evidence for tau lactylation in human AD brain tissue, we propose a testable hypothesis of intercellular metabolic crosstalk: lactate exported from highly glycolytic microglia may alter local lactate availability and provide an additional substrate for neuronal tau lactylation. Although the causal contribution of lactate from distinct cellular sources remains to be established, this framework provides a useful lens for interpreting coupled metabolic and epigenetic mechanisms in AD. Our future efforts should focus particularly on glycolytic flux, lactate, epigenetic writers/erasers, therapeutic approaches, and non-pharmacological approaches to stage- and cell-specific lactylation profiling, biomarker development, and the incorporation of metabolic and epigenetic endpoints into interventional studies.},
}

@article {pmid41910699,
year = {2026},
author = {Kushawaha, SK and Vashisht, K and Kumar, H and Anaklgi, AD and Ashawat, MS and Baldi, A},
title = {Sovateltide at the heart-brain axis crosstalk in Alzheimer's disease: a promising multi-target and cutting-edge therapeutic approach.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41910699},
issn = {1568-5608},
}

@article {pmid41910814,
year = {2026},
author = {Tripathi, P and Shah, J},
title = {Vitamin D3 Attenuates Alzheimer's Disease-Like Pathology via Remodeling Amyloid Protein Production and Clearance Pathway in Wistar Rats.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {},
pmid = {41910814},
issn = {1573-6903},
support = {GSBTM/MD/PROJECTS/SSA/4887/2016-17//Gujarat State Biotechnology Mission, Government of Gujarat, India/ ; },
mesh = {Animals ; *Alzheimer Disease/metabolism/drug therapy/pathology/chemically induced ; *Cholecalciferol/therapeutic use/pharmacology ; Male ; Rats, Wistar ; Rats ; *Amyloid beta-Peptides/metabolism ; Streptozocin ; Plaque, Amyloid/metabolism ; tau Proteins/metabolism ; },
abstract = {Alzheimer's disease widely affects millions of people worldwide, accounting for 60% of dementia cases. Clinically classified by the presence of cognition impairment, pathophysiological representation includes deposited senile plaques, neurofibrillary tangles, and neuroinflammation. The pathogenesis of Alzheimer's disease (AD) remains multifaceted and is governed by multiple hypotheses. However, it undeniably involves amyloid-β (Aβ) accumulation and hyperphosphorylated tau (p-tau) pathology as the crucial events in disease initiation. Substantial evidence has correlated Vitamin D3 as a vital supplementation for the prevention of dementia and delays the progression of AD. The presence of localized Vitamin D receptors (VDR) in the brain and their capacity to convert absorbed Vitamin D to its active form have established a robust link between Vitamin D3 and Alzheimer's disease. The current study aims to explore the role of Vitamin D3 on specific parameters related to Alzheimer's disease in the Streptozotocin ICV-induced sporadic AD rat model. The study protocol included a single bilateral ICV STZ intrahippocampal injection to induce AD, followed by 21 days of treatment with two different doses of Vitamin D3 or Calcitriol (1alpha,25-dihydroxyvitamin D3)i.e., 2.5 μg/kg and 5.0 μg/kg. Results demonstrated that Vitamin D3 attenuates AD-specific parameters of amyloid plaque (Aβ1-40 and Aβ1-42), p-tau, and BACE-1. Moreover, a significant increase in the levels of both neprilysin (NEP) and insulin-degrading enzyme (IDE) was observed, both of which play a crucial role in the clearance of senile plaques. Vitamin D3 treatment also demonstrated a significant improvement in cognitive performance, along with attenuation of neuroinflammatory and oxidative stress parameters. Conclusively, optimal levels of Vitamin D3 impart neuroprotection in AD by attenuating production and increasing clearance of amyloid proteins.},
}

Animals
*Alzheimer Disease/metabolism/drug therapy/pathology/chemically induced
*Cholecalciferol/therapeutic use/pharmacology
Male
Rats, Wistar
Rats
*Amyloid beta-Peptides/metabolism
Streptozocin
Plaque, Amyloid/metabolism
tau Proteins/metabolism

@article {pmid41910845,
year = {2026},
author = {Nekabari, MK and Ben-Azu, B and Chijioke, BS and Esuku, DT and Chidebe, EO and Friday, FB and Usin, SG and Iwhiwhu, P and Moses, AS and Diakparomre, O and Onyeukwu, OB},
title = {Lipopolysaccharide-induced Neuroimmune Alteration and Memory Decline in Aging Mice: The Role of Augmented Cellular Senescence.},
journal = {Neurotoxicity research},
volume = {44},
number = {2},
pages = {},
pmid = {41910845},
issn = {1476-3524},
}

@article {pmid41910849,
year = {2026},
author = {Akram, SW and K, C},
title = {Enhancing Parkinson's Disease Staging: An Integrative Deep Learning Framework for Multimodal Feature Selection.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {2},
pages = {},
pmid = {41910849},
issn = {1559-1166},
mesh = {Humans ; *Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis ; *Deep Learning ; Neuroimaging/methods ; Magnetic Resonance Imaging ; Male ; Female ; },
abstract = {Parkinson's disease (PD) affects 10 million globally, with accurate staging essential for personalized treatment planning. Current UPDRS assessments achieve < 93% accuracy due to subjective clinical judgment and unimodal data limitations, failing to capture complex genetic-neuroimaging-clinical interactions driving disease heterogeneity. This study introduces MAFNet, a novel deep learning framework pioneering Iterative Adaptive Vold-Kalman Filter (IAVKF) temporal denoising, Accelerated Binary Particle Swarm Optimization (ABPSO) swarm feature selection, Multilayer Perceptron-Lagrangian Support Vector Machine (MLP-LSVM) classification, and Graph-Attention Based Multimodal Fusion Network (GAMF). Applied to PPMI cohort (200 patients) with genetic SNPs (50), neuroimaging voxels (1,024), and UPDRS-III scores, the end-to-end pipeline delivers 97.6% accuracy, 98.2% precision, 96.8% recall, and 97.3% F1-score-outperforming CNN (92.4%), Autoencoder (90.8%), InceptoFormer (96.6%), and HCT (97.0%). IAVKF boosts SNR + 15.2dB (+ 2.9% accuracy vs. PCA/t-SNE); ABPSO reduces 1,276→340 features (73% reduction); regularization cuts overfitting gap to 0.9% (vs. 4.2% baseline). SHAP interpretability validates clinical plausibility (top predictors: LRRK2 SNPs, UPDRS-III tremor, hippocampal volume). Five-fold CV confirms stability with the Indian cohort external validation. Real-time inference (0.2s/patient, RTX 3090) enables clinical deployment. Future scope includes longitudinal temporal modelling, modality-agnostic fusion, edge deployment, federated learning, and extension to Alzheimer's/ALS. MAFNet transforms PD staging from subjective assessments to objective precision medicine, enabling biomarker discovery, progression forecasting, and personalized therapies across diverse global populations.},
}

Humans
*Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis
*Deep Learning
Neuroimaging/methods
Magnetic Resonance Imaging
Male
Female

@article {pmid41910964,
year = {2026},
author = {Banerjee, G and Mok, TH and Hyare, H and Cousins, O and Jaunmuktane, Z and Mead, S and Collinge, J},
title = {High-Level Alzheimer Disease Neuropathological Change Following Iatrogenic Exposure.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2026.0437},
pmid = {41910964},
issn = {2168-6157},
abstract = {IMPORTANCE: Alzheimer disease (AD) is pathologically characterized by the deposition of amyloid-β (Aβ) and hyperphosphorylated tau. Human transmission of Aβ pathology in a prion-like fashion has resulted in iatrogenic cerebral amyloid angiopathy. More recently, iatrogenic Alzheimer disease (iAD) was described in recipients of cadaveric pituitary-derived human growth hormone (c-hGH) contaminated with Aβ amyloid seeds.

OBJECTIVE: To describe the clinical and postmortem findings in iAD.

This case series describes 4 c-hGH recipients who were referred to the UK National Prion Clinic. Between February 2024 and February 2025, 14 c-hGH recipients had been referred to this service, with clinical assessments ongoing. The current study included 4 of 14 people treated with c-hGH who were referred since the original report. These data were analyzed during February and March 2025.

EXPOSURE: c-hGH contaminated with Aβ amyloid seeds.

MAIN OUTCOMES AND MEASURES: Clinical and histopathological description.

RESULTS: The study describes 4 males who developed dementia following confirmed or suspected c-hGH treatment in childhood (age at symptom onset between 47 and 60 years) with cognitive syndromes characterized by prominent language involvement. Results include clinical and postmortem findings for 1 patient (onset at age 47 years) in whom postmortem examination (at age 57 years) showed unequivocal neuropathological features of AD, including severe tauopathy. Brief descriptions of 3 additional patients with prominent language involvement are also provided.

CONCLUSIONS AND RELEVANCE: These results demonstrate that patients with iAD can have histopathological findings classically found in sporadic AD and that prominent language involvement might be an important phenotypic feature in this AD subtype.},
}

@article {pmid41910973,
year = {2026},
author = {Grill, JD and Raman, R and Wang, S and Ernstrom, K and Andrews, PS and Appleby, BS and Bhangu, J and Dhadda, S and Irizarry, M and Johnson, K and Lenio, S and MacDonald, S and Ramanan, VK and Rosenberg, PB and Weisman, D and Aisen, P and Sperling, R and Sultzer, D and Karlawish, J},
title = {Amyloid Imaging and APOE Genotype Disclosure and Short-Term Psychological Distress.},
journal = {JAMA network open},
volume = {9},
number = {3},
pages = {e263845},
doi = {10.1001/jamanetworkopen.2026.3845},
pmid = {41910973},
issn = {2574-3805},
mesh = {Humans ; Female ; Aged ; Male ; Middle Aged ; *Alzheimer Disease/genetics/psychology/diagnostic imaging ; Aged, 80 and over ; Positron-Emission Tomography ; Genotype ; *Apolipoproteins E/genetics ; *Psychological Distress ; Cohort Studies ; Biomarkers ; *Disclosure ; Amyloid ; },
abstract = {IMPORTANCE: Alzheimer disease (AD) biomarker and genetic testing results are increasingly disclosed to cognitively unimpaired adults in research and could in the future inform clinical treatment decisions in this population.

OBJECTIVES: To assess psychological outcomes after returning 3 categories of amyloid biomarker results as well as apolipoprotein E (APOE) genotypes.

This cohort study was a secondary analysis of data collected as part of screening for the multisite AHEAD preclinical AD trial. Participants were individuals aged 55 to 80 years undergoing screening from July 14, 2020, to October 15, 2024.

EXPOSURE: Participants were informed whether they had not-detected, intermediate, or elevated amyloid positron emission tomography levels, as well as their APOE genotype, which were categorized as noncarrier, ε4 heterozygote, or ε4 homozygote.

MAIN OUTCOMES AND MEASURES: Impact of Events Scale (IES; 15 items to assess intrusive thoughts and avoidance; each item is scored as not at all [0], rarely [1], sometimes [3], or often [5]; total range, 0-75), collected 24 to 72 hours after disclosure, and change in a scale measuring concerns about AD dementia (adapted scale using 6 items in which participants indicated their level of agreement with statements related to their perceived probability of developing AD dementia; items scored as strongly disagree [1] through strongly agree [5]; total range, 6-30), calculated by subtracting the score collected before biomarker testing from 1 collected after biomarker and genetic test results disclosure.

RESULTS: Among 3414 included individuals, the mean (SD) age was 68.8 (6.0) years and 2116 (62%) were female. Group mean IES scores were below clinically significant thresholds. Nevertheless, across genetic groups, learning an elevated amyloid result (1184 participants) was associated with higher IES (mean [SD], 10.5 [10.9]) than intermediate amyloid (482 participants; mean [SD] IES, 8.8 [9.8]), and intermediate amyloid was associated with higher scores than not-detected amyloid (1748 participants; mean [SD] IES, 6.5 [8.4]). Across amyloid groups, learning APOE ε4 homozygosity (337 participants) was associated with higher mean (SD) IES (12.7 [11.6]) than heterozygosity (1609 participants; 9.1 [10.2]), and heterozygosity was associated with higher IES than noncarrier status (1468 participants; mean [SD] IES, 6.2 [8.1]). Both types of information were significant in an analysis of covariance model; no interaction effect was observed. In contrast, only biomarker disclosure was associated with differential change in concerns about AD dementia. Those with elevated amyloid showed a mean (SD) increase in concern (0.8 [3.5]), those with intermediate amyloid showed a smaller increase (0.4 [3.7]), and those with not-detected amyloid showed decreased concerns (-1.1 [4.2]).

CONCLUSIONS AND RELEVANCE: In this cohort study of cognitively unimpaired adults, associations with intrusive thoughts were observed to differ among genetic and biomarker subgroups; such associations were limited to biomarker subgroups for measures of perceived dementia risk.},
}

Humans
Female
Aged
Male
Middle Aged
*Alzheimer Disease/genetics/psychology/diagnostic imaging
Aged, 80 and over
Positron-Emission Tomography
Genotype
*Apolipoproteins E/genetics
*Psychological Distress
Cohort Studies
Biomarkers
*Disclosure
Amyloid

@article {pmid41910991,
year = {2026},
author = {Appleby, BS and Cohen, ML},
title = {Signal, Speculation, and Standards of Proof in Iatrogenic Alzheimer Disease.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2026.0421},
pmid = {41910991},
issn = {2168-6157},
}

@article {pmid41911040,
year = {2026},
author = {Kaur, P and Kumari, S and Singh, AK and Koley, T and Rai, N and Samath, EA and Dey, S},
title = {Targeting GSK3β with a Synthetic Small Molecule Rescues Neurotoxicity in a Cellular Model of Alzheimer's Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00772},
pmid = {41911040},
issn = {1948-7193},
abstract = {The neuropathological presentation of Alzheimer's disease (AD) constitutes amyloid-β plaques and Tau tangles. Activation of GSK3β contributes to neurodegeneration by directly promoting tau hyperphosphorylation and amyloid-β formation. An earlier study also reported the overexpression of GSK3β in AD patients. This work designed and synthesized tetrapeptides [VYS(p)W, AKS(p)F, and DKS(p)F] containing a phosphate group attached to the serine residue, which mimicked the primed phosphorylated substrate of GSK3β. According to the network study, through interaction with various proteins and alteration of the molecular pathway of AD, the DKS(p)F peptide may exhibit a wide range of effects. The binding study of the peptide was performed by label-free surface plasmon resonance. The rescue effect of peptide on neurotoxicity was measured by MTT assay in SH-SY5Y cells. The peptide DKS(p)F was found to have the best docking score and binding energy with GSK3β. The low dissociation constant, (9.58 × 10[-8] M), indicates strongest binding capacity with GSK3β. The reduction in neurotoxicity of SH-SY5Y cells was observed after treatment with DKS(p)F by suppressing the levels of amyloid-β, Tau, and p-Tau proteins. This peptide can be one of the promising molecules for ongoing efforts to develop therapeutic molecules for the neurodegenerative disorder of Alzheimer's disease.},
}

@article {pmid41911062,
year = {2026},
author = {Rodwell-Bullock, J and Blau, E and Ganguly, A and Deaton, C and Johnson, GVW},
title = {BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00947.2025},
pmid = {41911062},
issn = {1522-1563},
support = {R01AG073121//HHS | NIH | National Institute on Aging (NIA)/ ; },
abstract = {Astrocytes maintain neuronal homeostasis by removing extracellular disease-relevant proteins, such as tau, to prevent their uptake by neurons. In Alzheimer's disease (AD), this astrocytic function is impaired, contributing to pathological tau accumulation. Many AD-associated risk genes are linked to endocytosis pathways, suggesting their role in AD pathogenesis. While astrocytes can internalize, degrade, and release tau, the mechanisms governing these processes remain unclear. Bcl2-associated athanogene 3 (BAG3), a multifunctional protein regulating vacuolar processes, interacts with components of clathrin-mediated endocytosis (CME), including clathrin heavy chain, dynamin, and AP-2 complex members. However, BAG3's role in astrocytic CME and tau processing is not fully understood. We demonstrate for the first time that BAG3 depletion in astrocytes reduces clathrin-AP-2 interactions, inhibits CME-dependent epidermal growth factor receptor internalization, and decreases tau uptake. Live-cell imaging reveals impaired CME dynamics with BAG3 depletion, marked by prolonged clathrin particle lifetimes. BAG3 depletion also increases Lamp1+ puncta and co-localization of tau with Lamp1-positive structures, indicating vacuolar disturbances beyond CME. These findings suggest BAG3 facilitates CME, tau uptake, and trafficking in astrocytes, playing a critical role in vacuolar processes and tau proteostasis. Alterations in astrocytic BAG3 may contribute to AD pathogenesis and other proteinopathies.},
}

@article {pmid41911088,
year = {2026},
author = {Kim, D and Lee, WJ and Jeon, DH and Lee, H and Kang, M and Park, M and Kim, M and Ha, S and Cho, K},
title = {Correlational Validity and Biomarker Associations of the Korean Computerized Cognitive Function Test (CFT-S) Relative to the Seoul Neuropsychological Screening Battery in MCI and Alzheimer's Disease.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000551744},
pmid = {41911088},
issn = {1421-9824},
abstract = {INTRODUCTION: This study evaluates the clinical validity of the Korean Computerized Cognitive Function Test (CFT-S) by comparing its domain-specific scores with those of the Seoul Neuropsychological Screening Battery-II (SNSB-II) in patients with Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD).

METHODS: A total of 300 participants (MCI: n = 163; AD: n = 137) from Severance Hospital completed both CFT-S and SNSB-II assessments within a two-week interval, along with brain MRI and APOE genotyping. Pearson correlations and multiple regression analyses examined relationships between cognitive scores and biomarker variables. Receiver operating characteristic curves assessed diagnostic accuracy. Bland-Altman plots evaluated agreement across five shared cognitive domains.

RESULTS: CFT-S index scores showed significant positive correlations with SNSB-II in attention, language, visuospatial, and executive domains (r = 0.59-0.71, p < 0.001). The memory domain showed a lower correlation in AD patients (r = 0.28), reflecting limitations under severe impairment. Hippocampal volume was positively associated with MMSE (r = 0.54), CFT-S memory (r = 0.50), and SNSB memory scores (r = 0.52). Education correlated with MMSE (r = 0.32) but not with CFT-S or SNSB, suggesting minimal education bias. APOE-ε4 carriers had smaller hippocampal volumes, higher FBB-PET BAPL scores, and poorer cognitive outcomes. The Bland-Altman plots demonstrated acceptable agreement at the group level between CFT-S and SNSB-II across all cognitive domains, with small mean biases and symmetric distributions despite relatively wide limits of agreement.

CONCLUSION: CFT-S index scores and Bland-Altman plot analysis demonstrated validity relative to SNSB-II, with significant associations to hippocampal atrophy and genetic risk factors. The findings support CFT-S as a viable and efficient cognitive assessment tool for diagnosing MCI and AD.},
}

@article {pmid41911308,
year = {2026},
author = {Xiong, X and Wang, X and Zhu, C and He, J and , },
title = {Disease progression modeling of Alzheimer's disease based on variational probability principal component analysis.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0342549},
doi = {10.1371/journal.pone.0342549},
pmid = {41911308},
issn = {1932-6203},
mesh = {Humans ; *Alzheimer Disease/pathology/diagnostic imaging/diagnosis/cerebrospinal fluid ; Disease Progression ; Male ; Aged ; Female ; *Principal Component Analysis ; Bayes Theorem ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Biomarkers/cerebrospinal fluid ; Aged, 80 and over ; Cognitive Dysfunction ; Neuroimaging ; Middle Aged ; Probability ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia. Early diagnosis and monitoring of disease progression are crucial for effective intervention. This study presents a novel disease progression model based on Variational Probabilistic Principal Component Analysis (VPPCA), which uses a Bayesian framework for dimensionality reduction and uncertainty quantification. By analyzing 1,021 amyloid-positive patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we extracted 25 features, including CSF (ABETA, TAU, PTAU), PET (FDG, AV45), and MRI volumetrics, along with cognitive and functional assessments. VPPCA compresses these multi-modal biomarkers into a single first principal component score (VPPCA1), which serves as a measure of disease progression. To ensure biological grounding and avoid circularity, we demonstrated that a VPPCA1 model using only non-cognitive features (CSF, PET, MRI, demographics) correlates strongly with cognitive decline (r = 0.658 with ADAS-Cog13), confirming that it captures genuine pathological progression rather than simply reflecting cognitive assessments. Block-wise feature ablation revealed that multi-modal integration is essential, with cognitive features showing the highest importance (0.1064), though all modalities contribute complementarily. In classification tasks, VPPCA exhibited strong performance with ROC-AUC values of 0.990 (CN vs Dementia), 0.774 (CN vs MCI), and 0.785 (MCI vs Dementia). A Bayesian hierarchical longitudinal model effectively captured patient-specific progression trajectories, offering personalized predictions of future disease states. VPPCA outperforms Probabilistic PCA (PPCA) by providing uncertainty quantification, with patient-specific confidence levels (σ = 0.086-0.136), which correlate with data quality, enabling automatic risk stratification. This work demonstrates that VPPCA offers a robust, biologically-grounded framework for modeling AD progression, providing actionable uncertainty quantification that improves clinical decision support and facilitates personalized care.},
}

Humans
*Alzheimer Disease/pathology/diagnostic imaging/diagnosis/cerebrospinal fluid
Disease Progression
Male
Aged
Female
*Principal Component Analysis
Bayes Theorem
Magnetic Resonance Imaging
Positron-Emission Tomography
Biomarkers/cerebrospinal fluid
Aged, 80 and over
Cognitive Dysfunction
Neuroimaging
Middle Aged
Probability

@article {pmid41911320,
year = {2026},
author = {Ali, S and Kuo, YF and Shan, Y and Tzeng, HM and Raji, MA},
title = {Impact of annual wellness visits on preventing falls and fractures for Alzheimer's disease and related dementias older adults.},
journal = {Age and ageing},
volume = {55},
number = {3},
pages = {},
doi = {10.1093/ageing/afag065},
pmid = {41911320},
issn = {1468-2834},
mesh = {Humans ; *Accidental Falls/prevention & control/statistics & numerical data ; Aged ; Female ; Male ; United States/epidemiology ; *Alzheimer Disease/complications/diagnosis/epidemiology ; Aged, 80 and over ; *Fractures, Bone/prevention & control/epidemiology/etiology ; Medicare ; Risk Factors ; *Dementia/complications ; Risk Assessment ; },
abstract = {BACKGROUND: Falls and fractures are leading causes of disability and premature death among older adults with Alzheimer's Disease and Related Dementias (ADRD). Annual Wellness Visits (AWVs), which Medicare reimburses, can screen and manage fall/fracture-related risk factors. This study evaluates the association between AWV and falls/fractures prevention among Medicare beneficiaries with ADRD.

METHODS: We analysed a cohort of Medicare beneficiaries in 2017 aged ≥68 years with ADRD and continuous enrollment from 2014 to 2016 (n = 1 610 637). AWV recipients were stratified by the number of visits before 2017 (0, 1, 2 or ≥ 3). Kaplan-Meier methods estimated rates of falls and fractures. Patients were censored at end of study (12/31/2021), if they lost Medicare coverage, or switched to HMO. We used inverse probability treatment weighting (IPTW) with propensity score in Cox proportional hazards models to assess the effect of AWVs.

RESULTS: AWVs were associated with reduced risks for falls (HR: 0.976 for 2 AWVs; 0.936 for ≥3 AWVs) and fractures (HR: 0.978 for 1 AWV; 0.960 for 2 AWVs; 0.927 for ≥3 AWVs), with greater reductions observed with more AVWs. Time-dependent models revealed AWV in follow-up period had stronger effects on fall and fracture risk (HR: 0.921 and 0.929, respectively). In subgroup analyses, AWV risk reduction was weaker for falls in Black and rural residents with no significant fracture risk reduction.

CONCLUSIONS: Our studies indicate more AWVs are associated with greater risk reduction of falls/fractures in older adults with ADRD. This study emphasizes expanding awareness of AWVs to prevent falls/fractures in this population.},
}

Humans
*Accidental Falls/prevention & control/statistics & numerical data
Aged
Female
Male
United States/epidemiology
*Alzheimer Disease/complications/diagnosis/epidemiology
Aged, 80 and over
*Fractures, Bone/prevention & control/epidemiology/etiology
Medicare
Risk Factors
*Dementia/complications
Risk Assessment

@article {pmid41911326,
year = {2026},
author = {Garcia Olivera, F},
title = {Proteome-based investigation of O-GlcNAcylation in a C. elegans model of ageing and Alzheimer's disease: Functional support for earlier hypothesis-generating findings.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0344865},
doi = {10.1371/journal.pone.0344865},
pmid = {41911326},
issn = {1932-6203},
mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics ; *Aging/metabolism ; *Proteome/metabolism ; *Acetylglucosamine/metabolism ; Disease Models, Animal ; *Caenorhabditis elegans Proteins/metabolism/genetics ; Protein Processing, Post-Translational ; Proteomics/methods ; tau Proteins/metabolism/genetics ; Animals, Genetically Modified ; Humans ; },
abstract = {O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins. The identity of O-GlcNAcylated proteins during ageing and neurodegenerative disease remains incompletely defined. Thus, animal models play a crucial role for the systematic characterization and cataloguing of O-GlcNAc-modified proteins. In this study, proteomic analysis was performed to identify O-GlcNAc-modified proteins in both L1 larval and adult stages of wild-type N2 and of aex-3p::Tau(V337M) transgenic Caenorhabditis elegans, a nematode model of ageing and Alzheimer's disease (AD) using high-resolution nano-LC-ESI mass spectrometry. O-GlcNAcylated proteins identified in the N2 strain were mapped to nuclear- and RNA-related processes in both stages. In the tau-expressing strain, functional enrichment analysis of the identified proteins indicated a predominance of stress-response-related pathways. Together, these data present an analysis of O-GlcNAc-modified proteins across early development, adulthood, and a tau-related C. elegans model, providing a resource for future functional and comparative studies of O-GlcNAcylation in ageing and AD.},
}

Animals
*Caenorhabditis elegans/metabolism/genetics
*Alzheimer Disease/metabolism/genetics
*Aging/metabolism
*Proteome/metabolism
*Acetylglucosamine/metabolism
Disease Models, Animal
*Caenorhabditis elegans Proteins/metabolism/genetics
Protein Processing, Post-Translational
Proteomics/methods
tau Proteins/metabolism/genetics
Animals, Genetically Modified
Humans

@article {pmid41911332,
year = {2026},
author = {Zhu, Z and Song, H and Liu, W and Tian, M and Hoang, T and Reddiar, SB and Trevaskis, NL and Han, S and Hu, L},
title = {Cervical Lymph Duct-Cannulated Rat Model for Assessing Lymphatic Transport from the Head and Brain.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {229},
pages = {},
doi = {10.3791/70217},
pmid = {41911332},
issn = {1940-087X},
mesh = {Animals ; Rats ; *Brain/metabolism ; *Lymphatic Vessels/physiology/metabolism ; *Head ; Neck ; Rats, Sprague-Dawley ; Models, Animal ; Male ; },
abstract = {Lymph flows from the central nervous system (CNS) via a series of lymphatic vessels (LVs) and lymph nodes that converge at the cervical lymph ducts. In addition to maintaining fluid balance, these lymphatic ducts play a key role in transporting a wide array of substances, including endogenous metabolites, signaling molecules, immune cells, and small and macromolecular drugs. This is critical for physiological homeostasis and immune function in both intracranial (e.g., brain) and extracranial regions (e.g., nasal and oral cavities). Impaired lymphatic drainage from the brain has increasingly been linked to a range of neurological and neurodegenerative disorders. Cervical lymph duct cannulation enables the collection of lymph draining the head and brain, allowing the measurement of the concentration and transport rate of various substances via the lymphatic system. Changes in these factors in response to different challenges (e.g., drugs, stress, trauma) and diseases (e.g., stroke, infection, Alzheimer's disease) can also be determined. Here, we describe an anesthetized, deep cervical lymph duct cannulated rat model that enables lymph collection for several hours following surgery. The method may be combined with imaging and multi-omics technologies for the measurement of a wide range of parameters of interest in the lymph. This facilitates fundamental physiological and pathophysiological research of the head and neck region, as well as pharmacokinetic/pharmacodynamic studies of drugs, particularly for the treatment of CNS diseases.},
}

Animals
Rats
*Brain/metabolism
*Lymphatic Vessels/physiology/metabolism
*Head
Neck
Rats, Sprague-Dawley
Models, Animal
Male

@article {pmid41911434,
year = {2026},
author = {Brotherhood, EV and El Baou, C and Fearn, C and Hayes, O and Zimmermann, N and Tsipa, A and Crutch, SJ and Stott, J},
title = {Factors Associated With the Use of Digital Health and Well-Being Resources in Non-Memory-Led Dementias: Quantitative Survey Study.},
journal = {JMIR aging},
volume = {9},
number = {},
pages = {e85863},
doi = {10.2196/85863},
pmid = {41911434},
issn = {2561-7605},
mesh = {Humans ; Male ; Female ; *Dementia/psychology/therapy ; Aged ; Middle Aged ; Surveys and Questionnaires ; Caregivers/psychology ; Aged, 80 and over ; Telemedicine ; Digital Health ; },
abstract = {BACKGROUND: Digital platforms disseminating health information and providing support for the experience of non-memory-led dementias (NMLDs) are invaluable. However, the factors influencing engagement with these resources in people affected by NMLDs are poorly understood. We conducted the world's largest survey exploring the experience of digital access in NMLDs to learn directly from people with a diagnosis, their care partners, and NMLD health care professionals (HCPs).

OBJECTIVE: This study aimed to determine factors associated with digital health and well-being resource use in people with NMLD and their care partners and investigate differences in digital health and well-being resource use according to NMLD subtype.

METHODS: Individuals diagnosed with NMLD-for example, those with frontotemporal lobar degeneration, posterior cortical atrophy (PCA), and primary progressive aphasia (PPA)-their care partners, and NMLD HCPs (N=450) responded to the survey. A subset of care partners provided two responses (carer-related and proxy), generating 4 survey groups with responses (N=538). The survey included demographics and basic clinical information, the outcome measure of usage behavior, and factors including constructs from the Short Senior Technology Acceptance Model (Short STAM) and additional constructs informed by a combination of previous literature and consultation with NMLD experts-by-experience (anxiety and depression [Patient Health Questionnaire-4-item], instrumental activities of daily living, web-related privacy and security concerns, and digital health literacy). Separate multiple linear regressions were run for each survey group to elucidate which variables predicted higher use of digital health and well-being resources. The use of digital resources for health and well-being was also explored across 3 NMLD subtypes: frontotemporal dementia (FTD), PPA, and PCA.

RESULTS: Attitudinal belief was consistently the strongest predictor of digital health and well-being resource use in people with NMLD as well as caregivers and proxy respondents. Control belief was significantly associated with higher digital health and well-being resource use in the NMLD and proxy groups; a trend was observed in the carer group. The adjusted R² range (63.0%-70.8%) denotes the variance in digital health and well-being resource use accounted for in the 3 models. Lower digital health and well-being resource use was associated with FTD diagnosis and caregiver groups relative to PPA and PCA.

CONCLUSIONS: Collectively, these findings indicate several factors are critical to consider when designing digital health and well-being resources for people with NMLD and their caregivers, in particular targeting practical and emotional perceptions of digital resource use for health and well-being. This should be undertaken in combination with design considerations that address condition-specific cognitive profiles encountered by those living with NMLD diagnoses and those who care for them.},
}

Humans
Male
Female
*Dementia/psychology/therapy
Aged
Middle Aged
Surveys and Questionnaires
Caregivers/psychology
Aged, 80 and over
Telemedicine
Digital Health

@article {pmid41911661,
year = {2026},
author = {Martínez, RF and Sánchez-Gallardo, M and Cintas, P},
title = {Memantine: A look ahead. Insights into structure, syntheses, receptor binding mechanisms, drug hybrids and formulations, and potential repurposing.},
journal = {European journal of medicinal chemistry},
volume = {310},
number = {},
pages = {118791},
doi = {10.1016/j.ejmech.2026.118791},
pmid = {41911661},
issn = {1768-3254},
abstract = {Since its approval for clinical use more than two decades ago, memantine has become a blockbuster drug against Alzheimer's disease (AD). Unlike other FDA approved small molecules for the treatment of AD, essentially acetyl cholinesterase inhibitors, memantine behaves as N-methyl-d-aspartate (NMDA) receptor antagonist. However, it is a weak and non-specific NMDA receptor channel blocker that has shown to be safe in slowing the decline of moderate to advanced AD symptoms. In fact, those of us familiarized with AD, are aware of clinical protocols where memantine is usually prescribed to mitigate late stages of this neurological disorder, following previous treatment with donepezil and other inhibitors. The role of memantine for either preventing or disrupting amyloid formation, yet promising, remains unconclusive. The pharmacological basis and mode of action of memantine are well known and have been reviewed from different standpoints, often within the context of adamantane scaffolds. In recent times, further analyses combining experiment and computational simulation have disclosed subtle features of memantine-receptor interactions and previously unrecognized mechanistic insights, which are summarized herein. Likewise, there is a growing interest in memantine derivatives, not only against neurodegeneration, but also versus unrelated pathologies. Such studies arising from lab observations and preclinical assessments at most, point to memantine's repurposing and open the door to further explorations and translation. It is noteworthy that some structural aspects of memantine, including crystal packing and polymorphism, are usually overlooked. This review pays attention to such key elements and updates synthetic protocols, including the first preparation of memantine in continuous flow.},
}

@article {pmid41912089,
year = {2026},
author = {Hoveizi, E and Karimi, A and Khajehpour, L and Ghotbeddin, Z and Pyecroft, S},
title = {Astrocyte-Derived Exosomes in Cognitive Recovery: A Comparative Assessment of Neurobehavioral, Molecular, and Electrophysiological Dimensions.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116196},
doi = {10.1016/j.bbr.2026.116196},
pmid = {41912089},
issn = {1872-7549},
abstract = {BACKGROUND: Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments in terms of efficacy, safety, and durability of effect. This study aimed to compare the therapeutic potential of astrocyte cells and their derived exosomes (AS-Exos) in restoring cognitive function in a mouse model of AD.

METHODS: AD model was induced by bilateral electrical lesioning of the nucleus basalis of Meynert (NBM). Astrocytes were isolated from neonatal rat brains, and AS-Exos were harvested from astrocyte-conditioned media using an AnaCell extraction kit. Seven days after lesion induction, astrocytes and AS-Exos were stereotaxically injected into the NBM. Four weeks later, behavioral assessments (passive avoidance and locomotor activity), electrophysiological recordings (EEG), and biochemical measurements of hippocampal brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels were performed.

RESULTS: AS-Exos were confirmed as cup-shaped vesicles (30-150nm) expressing the exosomal surface markers CD9, CD63, and CD81. NBM lesions significantly reduced step-through latency (STL), hippocampal BDNF and ACh levels, and disrupted EEG oscillatory patterns. Treatment with AS-Exos markedly improved STL and produced greater increases in hippocampal BDNF and ACh levels compared with AD and AD+saline groups. EEG analysis also revealed enhanced beta, alpha, and gamma power, with the most robust normalization observed in the AS-Exos group.

CONCLUSIONS: AS-Exos demonstrated superior biochemical and electrophysiological benefits compared with astrocyte transplantation and provided equal or greater improvement in behavioral outcomes. These findings highlight AS-Exos as a promising cell-free therapeutic strategy for alleviating cognitive deficits associated with AD.},
}

@article {pmid41912201,
year = {2026},
author = {Sabry, HH and Kadhum, BQ and Abdulmohsin, GN and El-Ghafar, AOA and Mahmoud, MM and Shams, GM},
title = {Cognitive Decline and Neurodegenerative Markers in Psoriasis: The Role of APOE4 and Beta-Amyloid.},
journal = {Dermatology practical & conceptual},
volume = {16},
number = {1},
pages = {},
doi = {10.5826/dpc.1601a5957},
pmid = {41912201},
issn = {2160-9381},
abstract = {INTRODUCTION: Psoriasis vulgaris (PV) is a chronic inflammatory skin disease increasingly recognized as a systemic disorder with potential cognitive implications. Amyloid beta (Aβ) and apolipoprotein E (APOE) are key proteins involved in Alzheimer's disease (AD) and neurodegeneration.

OBJECTIVES: This study investigated the relationship between PV, cognitive function, and serum levels of Aβ and APOE4.

METHODS: This case-control study was conducted on 80 participants: 50 PV patients and 30 age- and sex-matched controls. Clinical assessments included Psoriasis Area and Severity Index (PASI). Depression severity was assessed with Beck Depression Inventory-II (BDI-II), while cognitive function was evaluated using Montreal Cognitive Assessment (MoCA). Serum APOE4 and Aβ levels were measured using ELISA.

RESULTS: Patients with PV exhibited significantly higher levels of APOE4 (1125.5 ± 232.1 ng/ml vs. 821.8 ± 266 ng/ml, P<0.001) and Aβ (21.4 ± 2.2 ng/ml vs. 18.7 ± 1.4 ng/ml, P<0.001) compared to controls. ROC analysis identified APOE4 (AUC=0.80, P<0.001) and Aβ (AUC=0.86, P<0.001) as significant predictors of PV. MoCA scores were significantly lower in PV patients (median=22 vs. 28, P<0.001), particularly in those with severe disease. APOE4 and Aβ levels negatively correlated with cognitive function (r= -0.418, P=0.003), and (r= -0.399, P=0.004) respectively.

CONCLUSIONS: PV is associated with elevated Aβ and APOE4 levels, potentially linking chronic inflammation to neurodegeneration. The observed cognitive dysfunction in PV individuals underscores the importance of integrating neurological assessments into routine clinical evaluations.},
}

@article {pmid41912358,
year = {2026},
author = {Gai, J and Sharma, H and Kaskie, B and Jogerst, GJ},
title = {Evaluating the Effect of National Background Check Program on Nursing Home Deficiency Citations.},
journal = {Health services research},
volume = {61},
number = {2},
pages = {e70108},
doi = {10.1111/1475-6773.70108},
pmid = {41912358},
issn = {1475-6773},
support = {R21 AG082047/AG/NIA NIH HHS/United States ; },
mesh = {*Nursing Homes/standards/statistics & numerical data/organization & administration ; Humans ; United States ; *Elder Abuse/prevention & control/statistics & numerical data ; Aged ; *Quality of Health Care/statistics & numerical data ; Alzheimer Disease ; Dementia ; *Homes for the Aged/standards/statistics & numerical data ; Female ; },
abstract = {OBJECTIVE: To evaluate the impact of the National Background Check Program (NBCP) on nursing home (NH) health deficiencies and citations related to abuse, neglect, and exploitation.

STUDY SETTING AND DESIGN: This study uses the Callaway and Sant'Anna Difference-in-Differences (CSDID) quasi-experimental method to analyze data from US nursing homes from 2009 to 2016. The study includes nursing homes from 18 states that received NBCP grants as treatment group and nursing homes from 24 states that did not receive NBCP grants as control group. We exclude eight pilot NBCP states.

We used facility-level deficiency data from NH Care Compare (CC), NH characteristics data from Certification and Survey Provider Enhanced Reports (CASPER), and Alzheimer's Disease and Related Dementias diagnosis data from Minimum Data Set (MDS) assessments, covering 96,261 nursing home-year observations.

PRINCIPAL FINDINGS: Overall, NBCP implementation was associated with a significant reduction in health deficiencies (-0.760, p < 0.01) and a decrease in the probability and number of citations for abuse, neglect, and exploitation (-0.029, p < 0.01; -0.048, p < 0.01). Subgroup analyses showed that NBCP was associated with reductions in health deficiencies in nursing homes, regardless of whether they had a high or low census of residents with Alzheimer's Disease and Related Dementias, and in both metropolitan and nonmetropolitan areas. However, the effects varied across states depending on when they adopted NBCP.

CONCLUSIONS: Our findings suggest that NBCP is an effective regulatory tool for improving nursing home deficiencies and reducing incidents of abuse-related violations. We need more research to assess if background check programs improve nursing home quality using resident-level outcomes.},
}

*Nursing Homes/standards/statistics & numerical data/organization & administration
Humans
United States
*Elder Abuse/prevention & control/statistics & numerical data
Aged
*Quality of Health Care/statistics & numerical data
Alzheimer Disease
Dementia
*Homes for the Aged/standards/statistics & numerical data
Female

@article {pmid41912419,
year = {2026},
author = {Garcia, MA and Tarraf, W and Chiu, CT and Thierry, AD and Saenz, JL and Reyes, AM and Thorpe, RJ},
title = {A Comparison of Dementia-free Life Expectancy Estimates Across Competing Algorithmic Classifications: New Knowledge and Considerations from the Health and Retirement Study.},
journal = {The journals of gerontology. Series B, Psychological sciences and social sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/geronb/gbag051},
pmid = {41912419},
issn = {1758-5368},
abstract = {OBJECTIVES: To create new dementia-free life expectancy estimates based on three competing algorithmic classifications of dementia and compare these estimates with dementia-free life expectancy estimates based on the well-established Langa-Weir (LW) dementia classification to ascertain the consistency of competing algorithmic methods on the overall burden of quality of life measured by the number of years lived dementia-free and the proportion of late-life years dementia-free to total life expectancy.

METHODS: Data from the Health and Retirement Study (1998-2016) are used to estimate Sullivan-based life tables of dementia-free life expectancies by race/ethnicity, nativity, and gender for adults aged 70 and older. Dementia ascertainment was operationalized using the Langa-Weir (LW), Expert, Hurd, and LASSO classifications. We test for both within-group differences (i.e., nativity for Latinos) and gender differences to comprehensively document the overall burden of dementia among at-risk populations.

RESULTS: Expert, LASSO, and Hurd competing algorithm estimates were generally equal to the LW estimates for dementia prevalence after age 70, with a few exceptions. White men and women, and Black women exhibit better cognitive functioning in the LW model, whereas the results for other race/ethnic and nativity groups are more consistent across models.

DISCUSSION: Small differences in population-level estimates across algorithmic classification are observed; however, these small differences may be important for understanding disparities across groups. Therefore, more work is needed 1) to understand for whom and which models are most accurately identifying dementia and 2) to place these models relative to gold-standard adjudicated dementia assessments.},
}

@article {pmid41912452,
year = {2026},
author = {Duncan, S and Rehman, S and Segen, V and Choi, I and Lawrence, S and Kalani, O and Gold, L and Goldman, L and Ramlo, S and Stickel, K and Layfield, D and Wolbers, T and Tiganj, Z and Newman, EL},
title = {rTCT: Rodent Triangle Completion Task to Facilitate Reverse Translational Study of Path Integration.},
journal = {Hippocampus},
volume = {36},
number = {3},
pages = {e70090},
doi = {10.1002/hipo.70090},
pmid = {41912452},
issn = {1098-1063},
support = {R01 AG076198/NH/NIH HHS/United States ; //Indiana University Office for Vice President for Research bridge funding/ ; //Lilly Endowment, Inc., Indiana University Pervasive Technology Institute/ ; },
mesh = {Animals ; *Alzheimer Disease/physiopathology/psychology ; Male ; Rats ; *Spatial Navigation/physiology ; Disease Models, Animal ; Rats, Inbred F344 ; Translational Research, Biomedical/methods ; *Spatial Memory/physiology ; Maze Learning/physiology ; },
abstract = {Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimer's disease. In rodents, however, path integration is assessed using a wide variety of tasks, but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study, we developed and tested a novel rodent version of the triangle completion task to enhance cross-species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimer's disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.},
}

Animals
*Alzheimer Disease/physiopathology/psychology
Male
Rats
*Spatial Navigation/physiology
Disease Models, Animal
Rats, Inbred F344
Translational Research, Biomedical/methods
*Spatial Memory/physiology
Maze Learning/physiology