@article {pmid41538772,
year = {2026},
author = {Liao, YS and Wai, T and Liao, TY and Chang, HL and Chang, YL and Fu, LC},
title = {Mild Cognitive Impairment Detection System Based on Unstructured Spontaneous Speech: Longitudinal Dual-Modal Framework.},
journal = {JMIR medical informatics},
volume = {14},
number = {},
pages = {e80883},
doi = {10.2196/80883},
pmid = {41538772},
issn = {2291-9694},
mesh = {Humans ; *Cognitive Dysfunction/diagnosis ; Aged ; Male ; Female ; Longitudinal Studies ; *Speech ; Aged, 80 and over ; Memory, Episodic ; China ; },
abstract = {BACKGROUND: In recent years, the incidence of cognitive diseases has also risen with the significant increase in population aging. Among these diseases, Alzheimer disease constitutes a substantial proportion, placing a high-cost burden on health care systems. To give early treatment and slow the progression of patient deterioration, it is crucial to diagnose mild cognitive impairment (MCI), a transitional stage.

OBJECTIVE: In this study, we use autobiographical memory (AM) test speech data to establish a dual-modal longitudinal cognitive detection system for MCI. The AM test is a psychological assessment method that evaluates the cognitive status of subjects as they freely narrate important life experiences.

METHODS: Identifying hidden disease-related information in unstructured, spontaneous speech is more difficult than in structured speech. To improve this process, we use both speech and text data, which provide more clues about a person's cognitive state. In addition, to track how cognition changes over time in spontaneous speech, we introduce an aging trajectory module. This module uses local and global alignment loss functions to better learn time-related features by aligning cognitive changes across different time points.

RESULTS: In our experiments on the Chinese dataset, the longitudinal model incorporating the aging trajectory module achieved area under the receiver operating characteristic curve of 0.85 and 0.89 on 2 datasets, respectively, showing significant improvement over cross-sectional, single time point models. We also conducted ablation studies to verify the necessity of the proposed aging trajectory module. To confirm that the model not only applies to AM test data, we used part of the model to evaluate the performance on the ADReSSo dataset, a single time point semistructured data for validation, with results showing an accuracy exceeding 0.88.

CONCLUSIONS: This study presents a noninvasive and scalable approach for early MCI detection by leveraging AM speech data across multiple time points. Through dual-modal analysis and the introduction of an aging trajectory module, our system effectively captures cognitive decline trends over time. Experimental results demonstrate the method's robustness and generalizability, highlighting its potential for real-world, long-term cognitive monitoring.},
}

Humans
*Cognitive Dysfunction/diagnosis
Aged
Male
Female
Longitudinal Studies
*Speech
Aged, 80 and over
Memory, Episodic
China

@article {pmid41538578,
year = {2026},
author = {Khan, M and Saeed, U and Piracha, ZZ and Ozsahin, I and Shao-Chun, C},
title = {Innovative public-health strategies for neurodegenerative disease: leveraging diversified ultraviolet irradiation as a next-generation therapy.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {85},
number = {},
pages = {e297765},
doi = {10.1590/1519-6984.297765},
pmid = {41538578},
issn = {1678-4375},
mesh = {Humans ; *Neurodegenerative Diseases/radiotherapy/therapy ; *Ultraviolet Therapy/methods ; *Ultraviolet Rays ; *Public Health ; Oxidative Stress/radiation effects ; },
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis are escalating worldwide, straining healthcare systems and leaving patients with therapies that are largely palliative. Emerging evidence positions diversified ultraviolet (UV) irradiation as a groundbreaking, non-invasive strategy to counter these disorders. Beyond its traditional use in sterilization, specific UV spectra, UV-B (280-320 nm), UV-C (200-280 nm), and far-UV (207-222 nm), are now recognized for modulating oxidative stress, restoring mitochondrial function, correcting apoptotic dysregulation, and enhancing DNA repair. Innovative approaches such as riboflavin-mediated phototherapy and photobiomodulation (PBM) show the capacity to disaggregate toxic protein aggregates like β-amyloid and α-synuclein, boost antioxidant defenses, stimulate neurotrophic factors, and quell neuroinflammation. Preclinical models and early clinical trials reveal preserved cognition, enhanced neurogenesis, and reduced disease biomarkers, suggesting real translational promise. From a public-health perspective, UV-based interventions offer a cost-effective, scalable option for aging populations and resource-limited settings, especially when integrated with community-level health technologies and remote delivery platforms. Continued investigation of optimal dosing, long-term safety, and mechanistic pathways will be pivotal to unlock the full therapeutic and population-wide impact of this novel modality.},
}

Humans
*Neurodegenerative Diseases/radiotherapy/therapy
*Ultraviolet Therapy/methods
*Ultraviolet Rays
*Public Health
Oxidative Stress/radiation effects

@article {pmid41538324,
year = {2026},
author = {Dunn, LN and Niemeyer, BF and Eduthan, NP and Schade, KA and Waugh, KA and Brown, C and Rachubinski, AL and Timkovich, AE and Orlicky, DJ and Galbraith, MD and Espinosa, JM and Sullivan, KD},
title = {Altered hepatic metabolism in Down syndrome.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116835},
doi = {10.1016/j.celrep.2025.116835},
pmid = {41538324},
issn = {2211-1247},
abstract = {Trisomy 21 (T21) gives rise to Down syndrome (DS), the most commonly occurring chromosomal abnormality in humans. T21 affects nearly every organ and tissue system in the body, predisposing individuals with DS to congenital heart defects, autoimmunity, and Alzheimer's disease, among other co-occurring conditions. Here, using multi-omic analysis of plasma from more than 400 people, we report broad metabolic changes in the population with DS typified by increased bile acid levels and protein signatures of liver dysfunction. In a mouse model of DS, we demonstrate conservation of perturbed bile acid metabolism accompanied by liver pathology. Bulk RNA sequencing revealed widespread impacts of the Dp16 model on hepatic metabolism and inflammation, while single-cell transcriptomics highlighted cell types associated with these observations. Modulation of dietary fat profoundly impacted gene expression, bile acids, and liver pathology. Overall, these data represent evidence for altered hepatic metabolism in DS that could be modulated by diet.},
}

@article {pmid41537514,
year = {2025},
author = {McGoldrick, KE},
title = {Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.},
journal = {Anesthesiology},
volume = {143},
number = {6},
pages = {1672-1673},
pmid = {41537514},
issn = {1528-1175},
}

@article {pmid41537461,
year = {2026},
author = {Choi, KY and Kang, S and Cook, S and Li, D and Choi, YY and Seo, EH and Han, X and Park, JE and Lee, S and Lee, S and Chung, JY and Chong, A and Choi, SM and Ha, JM and Song, MK and Lee, JS and Choo, IH and Kim, JH and Song, HC and Kim, BC and Kim, H and Farrer, LA and Gim, J and Jun, GR and Lee, KH},
title = {The Gwangju Alzheimer's & Related Dementias (GARD) cohort: Over a decade of Asia's largest longitudinal multimodal study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70981},
doi = {10.1002/alz.70981},
pmid = {41537461},
issn = {1552-5279},
support = {25-BR-03-05//the KBRI Basic Research Program through the Korea Brain Research Institute, funded by the Ministry of Science and ICT/ ; NRF-2014M3C7A1046041//the Original Technology Research Program for Brain Science of the National Research Foundation funded by the Korean government, MSIT/ ; RS-2024-00407198//Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea/ ; 2023-ER1007-01//Korea National Institute of Health research project/ ; //by the Technology Innovation Program (20022810, Development and Demonstration of a Digital System for the evaluation of geriatric Cognitive impairment) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea)/ ; RS-2024-00433283//the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy, Republic of Korea/ ; HR22C141105//Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea/ ; },
mesh = {Humans ; Longitudinal Studies ; Male ; *Alzheimer Disease/epidemiology/diagnostic imaging/genetics/diagnosis ; Female ; Aged ; *Cognitive Dysfunction/epidemiology/diagnostic imaging ; Disease Progression ; Republic of Korea/epidemiology ; Cohort Studies ; Middle Aged ; Biomarkers ; Magnetic Resonance Imaging ; Aged, 80 and over ; Neuroimaging ; Proteomics ; Genomics ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a major public health concern in Korea, with a high prevalence among older adults. A community-based longitudinal study is essential for tracking disease progression, identifying biomarkers, and developing targeted prevention and treatment strategies. The Gwangju Alzheimer's & Related Dementias (GARD) cohort was established to address these needs through a multimodal approach.

METHODS: Participants aged ≥60 years undergo comprehensive clinical evaluations, neuroimaging, and biospecimen collection for multi-omics analyses (genomics, transcriptomics, proteomics, and metagenomics) at baseline and systematic follow-up visits.

RESULTS: From over 17,000 screened individuals, 12,877 were enrolled. Baseline diagnoses include 5,123 cognitively unimpaired (CU), 3,250 mild cognitive impairment (MCI), and 2,125 AD dementia. The resource includes magnetic resonance imaging scans (n = 10,843) and extensive multi-omics data: genomic (n = 10,775), proteomic (n = 116), and microbiome (n = 595).

DISCUSSION: The integrated GARD dataset provides a powerful and scalable resource for identifying novel biomarkers, understanding disease heterogeneity, and advancing precision medicine for AD.

HIGHLIGHTS: Gwangju Alzheimer's & Related Dementias (GARD) is a large-scale, longitudinal, community-based cohort study in South Korea. The study focuses on early detection and monitoring of dementia progression. GARD includes cognitive testing, imaging, biospecimens, and multi-omics data. We aim to identify Korean-specific biomarkers predictive of cognitive decline. Supports East Asian insights and fills gaps in global Alzheimer's research.},
}

Humans
Longitudinal Studies
Male
*Alzheimer Disease/epidemiology/diagnostic imaging/genetics/diagnosis
Female
Aged
*Cognitive Dysfunction/epidemiology/diagnostic imaging
Disease Progression
Republic of Korea/epidemiology
Cohort Studies
Middle Aged
Biomarkers
Magnetic Resonance Imaging
Aged, 80 and over
Neuroimaging
Proteomics
Genomics

@article {pmid41537459,
year = {2026},
author = {Ren, J and Pan, W},
title = {Large-Scale Genotype-Based Trait Imputation With Multi-Ancestry GWAS Data.},
journal = {Genetic epidemiology},
volume = {50},
number = {1},
pages = {e70030},
doi = {10.1002/gepi.70030},
pmid = {41537459},
issn = {1098-2272},
support = {U01 AG073079/NH/NIH HHS/United States ; R01 AG065636/NH/NIH HHS/United States ; RF1 AG067924/NH/NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; Alzheimer Disease/genetics ; Genotype ; Polymorphism, Single Nucleotide ; Models, Genetic ; Phenotype ; United Kingdom ; White People/genetics ; },
abstract = {Genome-wide association studies (GWAS) have been instrumental in identifying genetic variants associated with complex traits and diseases, including Alzheimer's disease (AD). However, traditional GWAS approaches often focus on European populations, which may lead to loss of power and limit the generalizability of findings across diverse ancestries. On the other hand, LS-Imputation, a nonparametric trait imputation method, leverages GWAS summary statistics and genotype data to impute missing traits, which can then be used for GWAS and other downstream analyses. Although LS-Imputation has been applied successfully to European populations, its performance in non-European populations would be hindered by smaller sample sizes, leading to reduced imputation accuracy. To address these limitations, we propose two novel variants of LS-Imputation-LS-Imputation-Combined and LS-Imputation-Transfer-designed to integrate multi-ancestry GWAS data and enhance imputation performance. LS-Imputation-Combined optimally combines GWAS summary statistics from multiple ancestries, while LS-Imputation-Transfer sequentially refines imputed trait values across ancestries using stochastic gradient descent. We evaluate these methods using data from the UK Biobank and the Alzheimer's Disease Sequencing Project (ADSP), first applying them to high-density lipoprotein (HDL) cholesterol levels as a proof-of-concept before focusing on imputing AD status in Black individuals for genetic association analysis. Our results demonstrate that integrating multi-ancestry GWAS data improves trait imputation accuracy, with LS-Imputation-Transfer achieving the highest performance.},
}

Humans
*Genome-Wide Association Study/methods
Alzheimer Disease/genetics
Genotype
Polymorphism, Single Nucleotide
Models, Genetic
Phenotype
United Kingdom
White People/genetics

@article {pmid41537452,
year = {2026},
author = {Herd, P and Sicinski, K and Williams, V and Asthana, S and Engelman, M},
title = {Early-life influences on the risk for later-life Alzheimer's and non-Alzheimer's dementia: A nearly full life course prospective cohort study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70967},
doi = {10.1002/alz.70967},
pmid = {41537452},
issn = {1552-5279},
support = {/NH/NIH HHS/United States ; 2R01AG060737//National Institute on Aging "Initial Lifetime Incidence of Alzheimer's Disease in the Wisconsin Longitudinal Study/ ; R24AG077433//"Network on Education, Biosocial Pathways, and Dementia across Populations/ ; R24AG077433/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology ; Female ; Male ; Risk Factors ; Prospective Studies ; Educational Status ; Longitudinal Studies ; Aged ; *Dementia/epidemiology ; Cognitive Reserve ; Wisconsin/epidemiology ; Aged, 80 and over ; Middle Aged ; Cohort Studies ; },
abstract = {BACKGROUND: Dementia prevention research has largely used educational attainment as a proxy for early-life. Given the known influence of early-life exposures on brain development, more attention to early-life exposures is warranted.

METHODS: We employ the Wisconsin Longitudinal Study, a nearly full life course cohort study, to examine the influence of prospectively measured early-life risk factors for dementia in later life.

RESULTS: We find that early-life risk factors that precede high school completion, rather than early adulthood post-secondary schooling, exert influence on later-life dementia. Household parental resources influence non-Alzheimer's disease (AD), but not AD, dementia risk. In contrast, markers for adolescent cognitive reserve (cognitive and academic performance measures) influence AD dementia risk, in part, by modifying genetic risk.

DISCUSSION: Using education as a proxy for early-life exposures conceals specific mechanisms that influence distinct dementia etiologies and are separately intervenable. Education's influence may be confined to the early-life and adolescent period, where brain development is especially malleable.

HIGHLIGHTS: Educational attainment is commonly used as a proxy for early-life risk factors for dementia. Given known early-life influences on brain development, more attention to the period is warranted. Early-life parental income influences non-AD dementia risk. Early-life cognition and academic performance influence AD dementia risk. Using educational attainment as a proxy for early-life exposures conceals separate intervenable risk factors.},
}

Humans
*Alzheimer Disease/epidemiology
Female
Male
Risk Factors
Prospective Studies
Educational Status
Longitudinal Studies
Aged
*Dementia/epidemiology
Cognitive Reserve
Wisconsin/epidemiology
Aged, 80 and over
Middle Aged
Cohort Studies

@article {pmid41537429,
year = {2026},
author = {Zhang, S and Liesz, A},
title = {Trained immunity in acute and chronic neurological diseases.},
journal = {eLife},
volume = {15},
number = {},
pages = {},
doi = {10.7554/eLife.106037},
pmid = {41537429},
issn = {2050-084X},
support = {EXC 2145 SyNergy//German Research Foundation/ ; Consolidator GRANT TRAINED ID 101229857/ERC_/European Research Council/International ; },
mesh = {Humans ; *Immunity, Innate ; *Nervous System Diseases/immunology ; Animals ; Chronic Disease ; Brain/immunology/pathology ; Acute Disease ; Trained Immunity ; },
abstract = {Trained immunity, the long-term reprogramming of innate immune cells to elicit an enhanced response upon subsequent challenges, has become a key concept in understanding a wide range of pathologies, including both acute and chronic inflammatory disorders. Recent evidence suggests that trained immunity also plays a significant role in the development and progression of various neurological disorders and related comorbidities, in which brain pathology can lead to trained immunity. This review summarizes the current understanding of trained immunity within both brain-resident immune cells and myeloid-derived innate immune cells, focusing on their roles in neurological disorders, such as ischemic brain injury, Parkinson's disease, and Alzheimer's disease. Additionally, we explore the heterogeneity of trained immunity across different conditions and its potential applications in clinical neurology.},
}

Humans
*Immunity, Innate
*Nervous System Diseases/immunology
Animals
Chronic Disease
Brain/immunology/pathology
Acute Disease
Trained Immunity

@article {pmid41537338,
year = {2026},
author = {Hibar, DP and Bauer, A and Rabe, C and Borlinghaus, N and Jethwa, A and Kollmorgen, G and Di Domenico, A and Zetterberg, H and Blennow, K and Masters, CL and Sperling, RA and Bittner, T},
title = {Elecsys pTau217 plasma immunoassay detection of amyloid pathology in clinical cohorts.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71009},
doi = {10.1002/alz.71009},
pmid = {41537338},
issn = {1552-5279},
support = {#2023-00356//Swedish Research Council/ ; #2022-01018//Swedish Research Council/ ; #2019-02397//Swedish Research Council/ ; 101053962//European Union's Horizon Europe Research and Innovation Programme/ ; #ALFGBG-71320//Swedish State Support for Clinical Research/ ; //F. Hoffmann-La Roche Ltd./ ; },
mesh = {Humans ; *tau Proteins/blood ; Female ; Male ; Immunoassay/methods ; Aged ; Cohort Studies ; Positron-Emission Tomography ; *Cognitive Dysfunction/blood/diagnosis ; Biomarkers/blood ; Phosphorylation ; Aged, 80 and over ; *Alzheimer Disease/blood/diagnosis ; *Amyloid beta-Peptides ; Middle Aged ; },
abstract = {INTRODUCTION: We evaluated the clinical performance of the fully automated, high-throughput, prototype Elecsys[®] Phospho-Tau (217P) plasma immunoassay (Roche Diagnostics) for detecting amyloid pathology.

METHODS: Plasma tau phosphorylated at threonine 217 (pTau217) levels were determined in samples from cognitively impaired and unimpaired individuals from five cohorts (N = 2148) using the pTau217 plasma immunoassay. Clinical performance was evaluated against amyloid positron emission tomography.

RESULTS: For cognitively impaired, mean plasma pTau217 levels for amyloid-positive (A+) individuals were higher (n = 394; 0.835 pg/mL) than amyloid-negative (A-) individuals (n = 144; 0.361 pg/mL); similarly, for cognitively unimpaired, A+ (n = 224; 0.516 pg/mL) and A- individuals (n = 1386; 0.220 pg/mL). Area under the curve was 0.878 (95% confidence interval [CI] 0.840, 0.915; impaired) and 0.907 (95% CI 0.885, 0.929; unimpaired). A cutoff < 0.189 pg/mL reliably ruled out individuals without amyloid pathology. High negative predictive values (92.51% [impaired]; 98.60% [unimpaired]) were observed with sensitivity/specificity of 98.98%/29.17% and 95.54%/50.72%, respectively.

DISCUSSION: The pTau217 plasma immunoassay accurately detects amyloid pathology, irrespective of cognitive status.

TRIAL REGISTRATION NUMBER: A4, NCT02008357; SKYLINE, NCT05256134; AIBL, SAGE Project ID Number: 2022/PID06188; SVHM Local Ref ID: HREC 028/06; CREAD, NCT02670083; CREAD2, NCT03114657 HIGHLIGHTS: The Elecsys[®] pTau217 plasma immunoassay (Roche Diagnostics) was evaluated across five cohorts. The pTau217 plasma immunoassay demonstrated high performance in detecting amyloid pathology in both cognitively impaired and unimpaired individuals. The pTau217 plasma immunoassay had a high negative predictive value which supports its utility as a pre-screening tool for Alzheimer's disease (AD). The pTau217 plasma immunoassay cutoffs identified are suitable for use as rule-out pre-screener tools in clinical trials. These findings reinforce the value of the high-throughput pTau217 plasma immunoassay measurements to aid AD diagnosis.},
}

Humans
*tau Proteins/blood
Female
Male
Immunoassay/methods
Aged
Cohort Studies
Positron-Emission Tomography
*Cognitive Dysfunction/blood/diagnosis
Biomarkers/blood
Phosphorylation
Aged, 80 and over
*Alzheimer Disease/blood/diagnosis
*Amyloid beta-Peptides
Middle Aged

@article {pmid41537308,
year = {2026},
author = {Yao, M and Tian, P and Li, X and Bian, S and Wang, G and Gu, Y and Navas-Acien, A and Vardarajan, BN and Belsky, DW and Miller, GW and Baccarelli, AA and Liu, Z},
title = {CoxMDS: multiple data splitting for high-dimensional mediation analysis with survival outcomes in epigenome-wide studies.},
journal = {Briefings in bioinformatics},
volume = {27},
number = {1},
pages = {},
doi = {10.1093/bib/bbaf730},
pmid = {41537308},
issn = {1477-4054},
support = {R01AG086379/NH/NIH HHS/United States ; },
mesh = {Humans ; *DNA Methylation ; Lung Neoplasms/genetics/mortality ; *Epigenome ; CpG Islands ; Proportional Hazards Models ; Alzheimer Disease/genetics/mortality ; *Epigenomics/methods ; Survival Analysis ; Genome-Wide Association Study ; Smoking/genetics/adverse effects ; *Mediation Analysis ; },
abstract = {Causal mediation analysis investigates whether the effect of an exposure on an outcome operates through intermediate variables known as mediators. Although progress has been made in high-dimensional mediation analysis, current methods do not reliably control the false discovery rate (FDR) in finite samples, especially when mediators are moderately to highly correlated or follow non-Gaussian distributions. These challenges frequently arise in DNA methylation studies. We introduce CoxMDS, a multiple data splitting method that uses Cox proportional hazards models to identify putative causal mediators for survival outcomes. CoxMDS ensures finite-sample FDR control even in the presence of correlated or non-Gaussian mediators. Through simulations, CoxMDS is shown to maintain FDR control and achieve higher statistical power compared with existing approaches. In applications to DNA methylation data with survival outcomes, CoxMDS identified eight CpG sites in The Cancer Genome Atlas that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on lung cancer survival, and two CpG sites in the Alzheimer's Disease Neuroimaging Initiative that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on time to Alzheimer's disease conversion.},
}

Humans
*DNA Methylation
Lung Neoplasms/genetics/mortality
*Epigenome
CpG Islands
Proportional Hazards Models
Alzheimer Disease/genetics/mortality
*Epigenomics/methods
Survival Analysis
Genome-Wide Association Study
Smoking/genetics/adverse effects
*Mediation Analysis

@article {pmid41536850,
year = {2026},
author = {Okhravi, HR and Fang, F and Hunter, MP and Sheehan, BE},
title = {Effect of antipsychotic medication use and type on mortality and cardiovascular risks in nursing home patients with dementia.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70247},
doi = {10.1002/dad2.70247},
pmid = {41536850},
issn = {2352-8729},
abstract = {INTRODUCTION: Antipsychotic medication (APM) use in nursing home (NH) patients with dementia is common but carries risks. This study assessed the association between APM use and mortality, stroke, and myocardial infarction (MI) compared to non-use, as well as differences between first- and second-generation APMs.

METHODS: A serial cross-sectional study using Medicare data examined outcomes from 2012 to 2015 in a national sample of 328,138 US NH residents aged 50 and older with dementia. Multivariate logistic regressions were used to analyze risk.

RESULTS: APM use was associated with increased mortality in all years (odds ratio [OR] range: 2.39 to 1.23, all p < 0.001) and stroke risk from 2012 to 2014 (OR range: 1.17 to 1.10, p < 0.01) but not MI. First-generation APMs posed a higher mortality risk than second-generation APMs, with no significant stroke or MI differences.

DISCUSSION: Findings highlight the need for cautious APM use in dementia patients in NHs due to elevated mortality and stroke risks.

HIGHLIGHTS: Study provides insights into APM risks in underrepresented nursing home (NH) dementia population.APM use in NH dementia patients is linked to higher death risk.First-generation APMs showed higher mortality risk than second-generation APMs.Overall, APM use is associated with increased stroke risk.No association was found between APM use and MI risk overall.},
}

@article {pmid41536849,
year = {2026},
author = {Nakashima, S and Sato, K and Niimi, Y and Ihara, R and Ikeuchi, T and Ishii, K and Ito, K and Iwata, A and Kasuga, K and Kato, T and Kowa, H and Nakase, T and Senda, M and Suzuki, K and Tomita, N and Tsukamoto, T and Yoshiyama, K and Toda, T and Iwatsubo, T},
title = {Characterizing Japanese older adults without dementia by amyloid PET status: A comparative study of amyloid-positive and amyloid-negative groups from Japanese trial-ready cohort study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70242},
doi = {10.1002/dad2.70242},
pmid = {41536849},
issn = {2352-8729},
abstract = {INTRODUCTION: This study aimed to identify demographic and cognitive differences based on amyloid status in older Japanese adults without dementia, addressing the lack of data in East Asian populations for early Alzheimer's disease (AD) detection.

METHODS: Analyzed baseline data from 630 participants from the Japanese Trial-Ready Cohort (J-TRC) study, all with a Clinical Dementia Rating-Global Score (CDR-GS) of 0 or 0.5. Amyloid status (Aβ+ or Aβ-) was determined by amyloid positron emission tomography (PET) scans.

RESULTS: Among participants, 24.8% were Aβ+. In the cognitively unimpaired (CDR-GS 0) group, Aβ+ individuals reported slightly greater self-perceived cognitive concerns (Cognitive Function Instrument [CFI-self]). For those with mild impairment (CDR-GS 0.5), Aβ+ status was associated with worse clinical scores, greater cognitive complaints, more depressive symptoms, and poorer memory and global cognition.

DISCUSSION: These findings align with major Western studies, emphasizing that CFI-self is a valuable tool for identifying early AD pathology across diverse populations.

HIGHLIGHTS: Comparing characteristics by amyloid status in Japanese non-demented older adults.Positron emission tomography-positive (PET+) scans in cognitively unimpaired individuals were associated with Cognitive Function Instrument-negative (CFI-) participants.PET+ in mild cognitive impairment (MCI) was linked to functional, cognitive, and affective decline.CFI- participants will aid early Alzheimer's pathology detection in diverse groups.},
}

@article {pmid41536772,
year = {2025},
author = {He, C and Zhou, Y and Chen, Y and Jing, Y},
title = {Research on interpretable machine learning models for diagnosis and staging of mild cognitive impairment.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1708525},
doi = {10.3389/fneur.2025.1708525},
pmid = {41536772},
issn = {1664-2295},
abstract = {BACKGROUND: Mild cognitive impairment (MCI) is a critical prodromal stage of Alzheimer's disease (AD), further categorized into early MCI (EMCI) and late MCI (LMCI). Early and accurate diagnosis is essential for effective prevention and intervention of AD. This study aims to develop an accessible and interpretable machine learning model to facilitate early diagnosis and subtype staging of MCI.

METHODS: A total of 268 participants were recruited from the ADNI, including cognitively normal individuals (CN, n = 132), EMCI (n = 95), and LMCI (n = 41). Participants were randomly divided into training (80%) and testing (20%) cohorts. Multimodal data encompassing whole-brain T1-WI MRI radiomics, clinical neuropsychological scales and plasma protein biomarkers were collected. Logistic regression (LR) and random forest (RF) algorithms were employed to construct six unimodal models based on above three categories of features, as well as a combined model combining all features. Diagnostic performance for the three-class classification task (CN, EMCI, LMCI) was evaluated using receiver operating characteristic (ROC) curve. Furthermore, SHapley Additive exPlanations (SHAP) were applied to quantify the contribution of individual features within the integrated model.

RESULTS: The combined model significantly outperformed unimodal models across all metrics, achieving macro_AUC = 0.92, micro_AUC = 0.91, and ACC = 0.81 in the training set, and macro_AUC = 0.87, micro_AUC = 0.87, and ACC = 0.76 in the testing set. The LR-based radiomics model ranked second. Models based solely on clinical neuropsychological scales or plasma protein biomarkers demonstrated comparatively lower classification performance. SHAP analysis highlighted neuropsychological scales (ADAS-Cog, MoCA) and radiomic features from critical brain regions (hippocampus, middle temporal gyrus, entorhinal cortex) as pivotal contributors to model efficacy.

CONCLUSION: The integration of whole-brain structural MRI (sMRI) radiomics, neuropsychological scales, and plasma protein biomarkers significantly improves the precision of diagnosing and staging mild cognitive impairment (MCI). Radiomic characteristics derived from critical cerebral regions yield valuable pathological information that facilitates clinical interpretation. This methodology presents a promising strategy for the early identification and individualized management of MCI.},
}

@article {pmid41536422,
year = {2025},
author = {Thaliath, A and Pillai, JA},
title = {Non-Cognitive Symptoms in Alzheimer's Disease and Their Likely Impact on Patient Outcomes. A Scoping Review.},
journal = {Current treatment options in neurology},
volume = {27},
number = {},
pages = {},
doi = {10.1007/s11940-025-00852-8},
pmid = {41536422},
issn = {1092-8480},
abstract = {PURPOSE OF REVIEW: Increased understanding of the pathophysiology of Alzheimer's disease (AD) has led to development of disease modifying therapies. The therapies primarily target measures of cognitive decline since AD has been thought of as a cognitive disorder. However, the non-cognitive symptoms seen in AD contribute to overall quality-of-life. This scoping review was undertaken to further our understanding of the non-cognitive features of AD.

RECENT FINDINGS: The non-cognitive symptoms in AD range from changes in sensory perception, systemic changes, and neuropsychiatric manifestations. We targeted the following non-cognitive domains: vision, olfaction, GI, muscle, sleep, circadian rhythm, immune and behavioral symptoms as it relates to AD for this review. Non-cognitive features impact the ability of individuals to perform their activities of daily living, have safety implications and lead to increased caregiver burden. The review explores non-pharmacological and pharmacological measures targeted at the non-cognitive changes in AD.

SUMMARY: Non-cognitive symptoms contribute to significant disease burden in Alzheimer's disease. It is important to screen for and provide supportive care for these symptoms to help improve clinical care. Incorporation of non-cognitive features of AD in clinical trials will help ascertain the true societal and economic impact of AD and that of potential therapeutics.

OPINION STATEMENT: Alzheimer's disease (AD) is primarily recognized as a disorder of cognition; however, non-cognitive symptoms significantly contribute to disease burden and clinical presentation. These manifestations particularly behavioral symptoms and systemic changes beyond the central nervous system impact patients' quality of life and increase caregiver stress. Often, such symptoms necessitate a transition from home-based care to more intensive settings, such as memory care facilities. As AD prevalence rises alongside an aging population, the shortage of dedicated memory care providers in community settings challenges access and quality of care. Improved awareness and early recognition of non-cognitive features among healthcare professionals can aid identification of modifiable systemic issues and allow timely behavioral management during clinical encounters. Treatment of these symptoms requires a multifaceted approach, incorporating pharmacological and non-pharmacological strategies. Non-pharmacological interventions, including tailored behavioral approaches and environmental modifications, can enhance quality of life for individuals with AD and reduce caregiver burden especially where specialized medical resources are limited.},
}

@article {pmid41536252,
year = {2026},
author = {Yaskolka Meir, A and Wang, X and Tasaki, S and Sarsani, V and Buchman, AS and Arnold, SE and Bennett, DA and Petyuk, VA and Liang, L and Capuano, AW and Arvanitakis, Z},
title = {Brain-peripheral proteome crosstalk in Alzheimer's disease with and without diabetes mellitus.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70959},
doi = {10.1002/alz.70959},
pmid = {41536252},
issn = {1552-5279},
support = {/AG/NIA NIH HHS/United States ; R01NS084965/NS/NINDS NIH HHS/United States ; RF1AG059621/NS/NINDS NIH HHS/United States ; R01AG074549/NS/NINDS NIH HHS/United States ; P30AG10161/NS/NINDS NIH HHS/United States ; P30AG072975/NS/NINDS NIH HHS/United States ; R01AG017917/NS/NINDS NIH HHS/United States ; U01AG61356/NS/NINDS NIH HHS/United States ; //Council for Higher Education/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology/complications ; Male ; Female ; *Proteome/metabolism ; *Diabetes Mellitus/metabolism/pathology ; Aged ; *Brain/metabolism/pathology ; Aged, 80 and over ; },
abstract = {BACKGROUND: Although considerable research has investigated diabetes mellitus (DM) as a risk factor for Alzheimer's disease (AD) dementia, the mechanistic understanding of the associations between peripheral and central biological processes in AD and AD within DM remains limited.

METHODS: We performed tandem mass tag-based phosphoproteome profiling on postmortem prefrontal cortex (n = 191), deltoid muscle (n = 191), and antemortem serum (n = 96) from older adults with/without pathologic AD and with/without DM (DM/NDM).

RESULTS: We observed significant brain-muscle and brain-serum correlations in phosphorylated and unphosphorylated peptides. Among individuals with DM, 59 were with AD and 36 were without. Among NDM, 63 were with AD and 33 were without. In a differential expression analysis, muscle phosphorylated seryl-tRNA synthetase 2 (SARS2)-S126 was significantly expressed in pathologic AD, whereas relative abundance of serum alpha-2-HS-glycoprotein (AHSG)-S346 and insulin-like growth factor binding protein 2 (IGFBP2)-S142 showed marginal expression for AD within the DM strata.

CONCLUSIONS: Elucidating central and peripheral proteome crosstalk is valuable for uncovering potential AD biomarkers in accessible (peripheral) biospecimens.

HIGHLIGHTS: We profiled peptides in brain, muscle, and serum biosamples. The study design allowed discovery of diabetes-associated peptides in Alzheimer's disease (AD). Strong brain-muscle, but weaker brain-serum peptide correlations were identified. Muscle seryl-tRNA synthetase 2-S126 was linked to AD pathology. Serum insulin-like growth factor binding protein 2-S142 and alpha-2-HS-glycoprotein-S346 were linked to AD in persons with diabetes.},
}

Humans
*Alzheimer Disease/metabolism/pathology/complications
Male
Female
*Proteome/metabolism
*Diabetes Mellitus/metabolism/pathology
Aged
*Brain/metabolism/pathology
Aged, 80 and over

@article {pmid41536249,
year = {2026},
author = {Ali, A and DeLong, A and Williams, LA and Henry, AP and Thorpe, R and Turner, RW},
title = {Lessons learned in the recruitment and retention of Black males in informal dementia caregiving research.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70939},
doi = {10.1002/alz.70939},
pmid = {41536249},
issn = {1552-5279},
support = {//the National Institute on Aging/ ; //3K01AG054762-03S1/ ; P30AG059298//the NIA/ ; P30AG059298/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Caregivers/psychology ; Male ; *Black or African American ; Middle Aged ; *Patient Selection ; *Dementia ; *Biomedical Research ; Pilot Projects ; Aged ; *Alzheimer Disease/nursing ; COVID-19 ; White ; },
abstract = {INTRODUCTION: Black American men are underrepresented in Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research. This article aims to provide a framework for recruiting Black men in biomedical research, particularly for AD/ADRD caregiver studies.

METHODS: We combined multiple recruitment strategies, both virtual, due to the COVID-19 pandemic, and in-person, that focused on a culturally informed community engagement approach. Through partnerships with local organizations, including faith-based groups, we developed recruitment strategies based on their expert recommendations.

RESULTS: Of the n = 180 participants recruited, n = 77 participated in this study, n = 37 caregivers and n = 40 non-caregivers. The mean age of participants was 58.17 years, and the average participant had earned a master's degree.

DISCUSSION: This pilot study encompassed a synergistic strategy approach that combined three methods to recruit, engage, and retain Black men in biomedical research. By recruiting underrepresented groups, we can gain insights into the unique needs these populations may face, leading to the development of more tailored interventions.

HIGHLIGHTS: To address barriers to participation, a culturally informed, community-based, relationship-guided approach guided by the health belief model was utilized. Focused recruitment, engagement, and retention efforts in the Washington, DC, metropolitan area attracted n = 180 Black male adults for an AD/ADRD informal caregiver research project. Through partnerships with local organizations, including faith-based organizations, we curated recruitment strategies based on their expert recommendations. We continuously foster cross-collaboration with participants to educate the public and ensure that vital information is included in the interpretation of results from a layman's perspective.},
}

Humans
*Caregivers/psychology
Male
*Black or African American
Middle Aged
*Patient Selection
*Dementia
*Biomedical Research
Pilot Projects
Aged
*Alzheimer Disease/nursing
COVID-19
White

@article {pmid41536214,
year = {2026},
author = {Wu, J and Su, B and Fan, Z and Zhan, H},
title = {Genetically Predicted HDL Traits and Pan-Disease Risk: A Systematic Review.},
journal = {Epidemiologic reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/epirev/mxag001},
pmid = {41536214},
issn = {1478-6729},
abstract = {High-density lipoprotein nHDL) is a highly heterogeneous lipoprotein with multiple physiological functions. However, observational studies present conflicting evidence regarding its association with various diseases. This study systematically summarizes evidence from Mendelian randomization (MR) studies to investigate the causal relationships between HDL-related biomarkers and a wide spectrum of disease outcomes. We systematically searched multiple databases up to November 2024. The causal relationship between HDL and 158 diseases was studied. Findings reveal that the role of HDL is highly disease-specific. Genetically predicted higher HDL levels are protective against the majority of circulatory and digestive system diseases. Conversely, they are associated with an increased risk of certain conditions, including breast cancer, intracerebral hemorrhage, and age-related macular degeneration. MR analyses revealed inconsistent and sometimes conflicting findings for several disease outcomes, notably including Alzheimer's disease. This review underscores the context-dependent nature of HDL's effects, which may be driven by factors like HDL particle heterogeneity and functional transformation into a pro-inflammatory state. Future research should move beyond concentration-based metrics to focus on HDL functionality and precise subtyping to fully understand its role in disease etiology.},
}

@article {pmid41536056,
year = {2026},
author = {Dong, J and Xu, L and Xu, X and Shi, B and Wang, Q and Xu, J and Xu, C and Kuang, H and Qu, A},
title = {Chiral Spindle-like Nanorods Reprogram Neuroinflammation by Catalyzing α-Ketoglutarate Biosynthesis.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c19753},
pmid = {41536056},
issn = {1520-5126},
abstract = {Alzheimer's disease (AD) is the most prevalent cause of dementia worldwide, and breakthroughs in effective intervention strategies are urgently needed. Here, we report that chiral spindle-like Fe7Se8 nanorods (NRs) promote α-ketoglutarate (AKG) biosynthesis, providing a new potential route for AD intervention through modulation of neuroimmune homeostasis. Oral administration of L-NRs significantly restored intestinal microbiota homeostasis in 3 × Tg AD model mice, markedly enriched Lactobacillus johnsonii, and enhanced biosynthesis of the metabolite AKG, which reversed cognitive impairment and neuronal degeneration in 5 × FAD mice. Moreover, AKG levels in the clinical serum and cerebrospinal fluids were found to be significantly lower in patients with AD than in healthy controls. Mechanistic studies revealed that L-NRs efficiently promoted AKG biosynthesis through scavenging reactive oxygen species (ROS) to restore the activities of three enzymes in the biosynthesis pathway. Crucially, these NRs are broken down by gastric juice into smaller nanoparticles and subsequently into ions in the intestines. Further studies explored that AKG crossed the blood-brain barrier via cooperatively mediated transport proteins, targeted microglial phenotypic switching, reprogrammed the neuroinflammatory microenvironment, and ultimately ameliorated cognitive deficits and neuronal pathological alterations. Our findings suggest that AKG might serve as a therapeutic drug for the precise treatment of neurodegenerative diseases.},
}

@article {pmid41536026,
year = {2026},
author = {Zhang, JY and Dregni, AJ and Hong, M},
title = {Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils.},
journal = {Journal of the American Chemical Society},
volume = {148},
number = {1},
pages = {1623-1637},
doi = {10.1021/jacs.5c18540},
pmid = {41536026},
issn = {1520-5126},
mesh = {*tau Proteins/chemistry/genetics/metabolism ; Humans ; Nuclear Magnetic Resonance, Biomolecular ; *Amyloid/chemistry ; },
abstract = {The β-sheet core of many amyloid proteins in neurodegenerative diseases is surrounded by dynamically disordered segments that contact cellular species. Recent data suggest that this "fuzzy coat" may also regulate the prion-like propagation of amyloid proteins. Here we report the site-specific dynamics of the fuzzy coat of a full-length tau fibril, assembled without anionic cofactors in the presence of four phospho-mimetic glutamate mutations at the PHF1 epitope of Alzheimer's disease tau. The rigid core structure of this 4E tau was recently determined to consist of three β-strands, resembling the structure of three-layered tau aggregates in certain tauopathies. Using solid-state and solution NMR, we measured chemical shifts, peak intensities, and motional amplitudes of the dynamic residues in this 4E tau fibril and investigated the polarization transfer between the dynamic and the rigid segments. These data indicate that the 4E tau fuzzy coat contains three types of dynamic residues: type-1 residues undergo fast large-amplitude motion, type-2 residues undergo fast but intermediate-amplitude motion, and type-3 residues undergo microsecond motion. We estimate the number of residues in each category and propose the likely model for the packing of this fuzzy coat around the rigid core. A truncated tau fibril with the same rigid-core structure as 4E tau shows different fuzzy coat dynamics, indicating that the rigid-core structure is insufficient for defining all the properties of the fibrils. Our fuzzy coat model provides insight into the potential mechanism of prion-like propagation of tau aggregates and suggests how cellular species bind pathological tau aggregates.},
}

*tau Proteins/chemistry/genetics/metabolism
Humans
Nuclear Magnetic Resonance, Biomolecular
*Amyloid/chemistry

@article {pmid41535911,
year = {2026},
author = {Ang, K and Chiu, FY and Lim, GZ and Chen, SJY and Lum, E},
title = {Adoption, scale-up, and sustainability of a neuropalliative care model: qualitative exploration of pre-implementation barriers and enablers.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-025-13835-x},
pmid = {41535911},
issn = {1472-6963},
abstract = {BACKGROUND: People with long-term neurological conditions such as Alzheimer's dementia and Parkinson's disease live with these increasingly debilitating conditions for years. However, palliative care is provided only towards the end of life. To address the gap between patient needs and services provided, we piloted an early neuro-palliative model of care - Neurosupport. In this study, we explored pre-implementation barriers and enablers for the adoption, scale-up, and sustainability of Neurosupport.

METHODS: We conducted semi-structured interviews using an interview guide based on the Theoretical Domains Framework. Participants were neurologists and healthcare professionals involved in the care of patients with long-term neurological conditions. Interviews were conducted between May and December 2021. We used deductive and inductive coding followed by code-mapping to arrive at themes.

RESULTS: Twenty-one participants were interviewed, comprising 12 neurologists, four neurology nurses, and five allied healthcare professionals (two speech therapists, one physiotherapist, one medical social worker, and one psychologist). Five themes were generated: (I) build rapport and support patients and families/caregivers; (II) current challenges, foreseeable barriers, and mitigation strategies; (III) unclear value-add of Neurosupport; (IV) integration of health and social services; and (V) implementing and sustaining Neurosupport.

CONCLUSION: This study elicited critical gaps and issues regarding the value proposition, workflows, and resources relevant to the implementation of Neurosupport. Future scale-up and sustainability of Neurosupport depend on these short-comings being addressed.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid41535718,
year = {2026},
author = {Silva-Spínola, A and Durães, J and de Oliveira, JPG and Tábuas-Pereira, M and Lima, M and de Mendonça, A and Santana, I and Baldeiras, I},
title = {Plasma p-tau217, quantified by the fully automated LUMIPULSE G platform, outperforms p-tau181 in predicting amyloid pathology in cognitive complaints patients.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-34241-7},
pmid = {41535718},
issn = {2045-2322},
support = {PT0056.A.02//Universidade de Coimbra/ ; EXPL/MEC-NEU/0192/2021//Fundação para a Ciência e a Tecnologia/ ; },
}

@article {pmid41535708,
year = {2026},
author = {Yu, MJ and Xiong, RQ and Wu, JW and Li, YC and Xie, JX and Zhou, HP and Ye, GY and Chang, Y and Huang, KB and Pan, SY},
title = {β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral edema in mice after ischemic stroke.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
pmid = {41535708},
issn = {1745-7254},
abstract = {Cerebral edema is a severe complication following ischemic stroke. Recent studies have highlighted the crucial role of the glymphatic system (GS) in the clearance of water and macromolecules. GS dysfunction involving the disorders of AQP4 polarization may be crucial in the pathophysiology of cerebral edema. β-Hydroxybutyrate (BHB), the main component of the ketone body, has been shown to alleviate neurological deficits by restoring GS function in subarachnoid hemorrhage models and to reduce Aβ deposition in Alzheimer's disease models. In this study we investigated the effects of BHB on cerebral edema following ischemic stroke and its mechanisms. The mice were fed a ketogenic diet (KD) or a normal diet for 4 weeks before transient middle cerebral artery occlusion (MCAO). Alternatively, the mice received BHB (5 g·kg[-1]·d[-1]) or vehicle post-MCAO. By using brain section analysis, transcranial macroimaging, two-photon in vivo imaging and MRI, we demonstrated that both KD and BHB treatment significantly enhanced GS function under normal and MCAO conditions. BHB reduced cerebral edema and infarct volume post-MCAO. Notably, delayed BHB treatment initiated 10 h post-MCAO still improved GS function, but did not influence infarct volume. Furthermore, we revealed that BHB increased α1-syntrophin expression and H3K27ac levels in α1-syntrophin (Snta1) enhancer, restoring AQP4 polarization. In addition, BHB also reduced HDAC3 expression and elevated p300 expression. These results suggest that a KD and BHB treatment enhance GS function in mice and that BHB also mitigates brain edema after MCAO. The potentiation of GS function by BHB is likely mediated by the inhibition of HDAC3 activity and the increase in p300 activity, which upregulate α1-syntrophin expression and restore AQP4 polarization.},
}

@article {pmid41535685,
year = {2026},
author = {Tognoni, CM and Ghosh Biswas, R and Suar, ZM and Carreras, I and Dedeoglu, A and Jenkins, BG},
title = {Protection of multiple aspects of Alzheimer's disease pathology using dietary supplementation with taurine.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-32797-y},
pmid = {41535685},
issn = {2045-2322},
support = {MFE-194064/CAPMC/CIHR/Canada ; 1RF1AG069228 ; 5R01AG070257/NH/NIH HHS/United States ; },
}

@article {pmid41535445,
year = {2026},
author = {Schnieder, M and von Arnim, CAF},
title = {[Polypharmacy in patients with neuropsychiatric symptoms].},
journal = {Innere Medizin (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {41535445},
issn = {2731-7099},
abstract = {Dementia, delirium, and depression are the main geriatric psychiatric syndromes, and their prevalence is increasing significantly due to demographic aging. At the same time, multimorbidity and polypharmacy lead to increased interaction rates and a higher frequency of side effects, as well as reduced adherence. In Germany, the number of dementia cases is projected to rise from the current 1.8 million to 2.8 million by 2050. The most common etiologies are Alzheimer's disease and vascular dementia. Progressive cognitive and motor function loss often results in apraxia and dysphagia, which complicate pharmacotherapy. Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine are used therapeutically. Newly approved amyloid antibodies (lecanemab, donanemab) show efficacy in the early stages of Alzheimer's disease, but carry the risk of amyloid-associated imaging abnormalities (ARIA). Dementia is considered a predisposing risk factor for delirium, which is characterized by fluctuations in attention and consciousness. Delirogenic factors include polypharmacy as well as other medications such as opioids and benzodiazepines. Due to the increased risk of mortality and stroke, neuroleptics should only be administered to geriatric patients when strictly indicated, in minimal doses, and for a limited duration. Non-pharmacological interventions take precedence. Selective serotonin reuptake inhibitors (SSRIs) are considered the first-line treatment for depressive disorders in older adults, while tricyclic antidepressants should be avoided. Regular medication reviews, reduction of anticholinergic burden, and technical aids to facilitate medication intake are essential for optimizing treatment adherence.},
}

@article {pmid41534833,
year = {2026},
author = {Mon, F and Straub, JE},
title = {Structural and mechanistic characterization of heparin interactions with tau fibrils.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111153},
doi = {10.1016/j.jbc.2026.111153},
pmid = {41534833},
issn = {1083-351X},
abstract = {Soluble microtubule-associated tau protein can misfold and assemble into stable, insoluble amyloid fibrils. The accumulation of tau amyloid fibrils within neurons is a primary feature in the progression of neurodegenerative diseases including Alzheimer's disease. Tau fibrils have been observed to colocalize with glycosaminoglycans such as heparan sulfate in vivo. Heparin is a highly sulfated analogue of heparan sulfate that has been commonly used in vitro to accelerate tau aggregation. Binding of heparin to tau fibrils inhibits fibril uptake by neighboring cells, whereas heparan sulfate on the cell surface modulates this uptake. Understanding the molecular interactions of heparin and heparan sulfate with tau fibrils is important in developing therapeutic targets that can slow the progression of neurodegeneration. In this multiscale computational study, we employ a combination of Brownian dynamics and molecular dynamics to simulate heparin binding to two tau fibril polymorphic structures. Our simulations lead to the de novo prediction of heparin binding to basic residue ladders organized along the tau fibril axis. The mechanism of binding is facilitated by long-range electrostatic steering of the polyanionic heparin to the tau fibril surface, followed by the refinement of favorable short-range heparin-tau interactions. The identified binding sites are located in regions of excess densities in cryo-EM maps of the tau fibrils, providing support for the computational predictions. Our findings provide a structural and mechanistic framework for a better understanding of fibril-glycan interactions and how they influence the overall mechanism of tau fibril propagation.},
}

@article {pmid41534832,
year = {2026},
author = {Han, L and Galizia, S and Pan, J and Bhattacharjee, M and Lagerlöf, O},
title = {O-GlcNAcase promotes dendritic spine morphogenesis while downregulating their GluA2-containing AMPA receptors.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111157},
doi = {10.1016/j.jbc.2026.111157},
pmid = {41534832},
issn = {1083-351X},
abstract = {Dendritic spines are essential for synaptic transmission, neural circuit organization, and cognitive function. Their morphology and density influence synaptic plasticity, learning, and memory. Many proteins in dendritic spines are modified with O-GlcNAc, a monosaccharide that can be attached and removed from serines and threonines. O-GlcNAc has been implicated in multiple brain disorders, yet the role of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc modification from proteins, in dendritic spine regulation remains unclear. This study examines the role of OGA in spine and synapse morphogenesis. Immunohistochemical and biochemical analyses reveal that OGA is present in dendritic spines. Functional assays show that OGA promotes spine maturation, increases spine density, and alters synapse size. Additionally, OGA modulates the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), down-regulating GluA2-containing receptors in developing and mature neurons. These findings highlight OGA as a key regulator of excitatory synaptic remodeling and a therapeutic target for synapse-related pathologies such as Alzheimer's disease and autism.},
}

@article {pmid41534821,
year = {2026},
author = {Cadaxo, AS and Cotrin, JC and Valente, AP and Lopes, FG and Veras, RP and Torres, DS and Molina da Costa, RQ and Dos Santos Junior, GC and Santos Rebouças, CB},
title = {Multi-biofluid metabolomics coupled with gene network reveals stage-specific alterations in mild cognitive impairment and Alzheimer's disease in an ethnically mixed cohort.},
journal = {Brain research},
volume = {},
number = {},
pages = {150167},
doi = {10.1016/j.brainres.2026.150167},
pmid = {41534821},
issn = {1872-6240},
abstract = {Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide. A prodromal stage, often manifested as Mild Cognitive Impairment (MCI), can precede dementia onset. Metabolomics provides a powerful approach to detect metabolic alterations capturing combined genetic, epigenetic, dietary, gut microbiota, and environmental influences on AD pathogenesis and progression from MCI to AD. In this study, we analysed plasma, urine, and saliva metabolomes of 94 ethnically diverse Brazilian individuals (30 AD, 16 MCI and 48 healthy controls), all comorbidity-free, using Nuclear Magnetic Resonance (NMR)-based metabolomics. Cross-sectional analysis employed multivariate modelling (PLS-DA) and univariate Mann-Whitney U tests. We identified distinct group-specific metabolic signatures involving amino acids (phenylalanine, glutamine, asparagine, valine, alanine), energy-related metabolites (pyruvate, citrate, glucose), compounds linked to lipid/redox pathways (acetate, glutamate, aspartate), epigenetic regulation (betaine), neuroinflammation, immune fitness, and gut microbiome-influenced metabolites (scyllo-inositol). Valine increased progressively (controls < MCI < AD), while alanine showed a biphasic pattern (reduced in MCI, elevated in AD). These consistent, biofluid-spanning alterations highlight their potential as minimally invasive biomarkers for diagnosis and monitoring. Integration of metabolite data with AD-associated genes from genome-wide association studies (GWAS) revealed six genes (CYCS, NFAT5, GRIN2B, SLC43A2, MAPT, and SLC38A1) common to all biofluids, reinforcing convergent systemic pathways. Collectively, these findings underscore the importance of integrating metabolomics with genetic networks to enhance understanding of AD pathophysiology, identify potential therapeutic targets, and guide future clinical validation and precision medicine strategies for dementia in ethnically mixed populations.},
}

@article {pmid41534749,
year = {2026},
author = {Yadav, V and Das, S and Murmu, A and Matore, BW and Satpathy, S and Mandal, V and Roy, PP and Singh, J and Patra, A},
title = {Therapeutic potential of Oxalis corniculata in circumventing Alzheimer's disease through in vitro and in silico investigations.},
journal = {Journal of ethnopharmacology},
volume = {360},
number = {},
pages = {121178},
doi = {10.1016/j.jep.2026.121178},
pmid = {41534749},
issn = {1872-7573},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disease wherein loss of memory and cognition is very common. Oxidative stress, lack of acetylcholine, and inflammation in brain tissues are characteristics of AD. Development of natural remedies such as medicinal plants for management of AD is a viable strategy.

AIM OF THE STUDY: In the present study, methanolic extract of Oxalis corniculata (MEOC) was examined for its beneficial role in management of AD by integrating in vitro and in silico experiments.

MATERIALS AND METHODS: MEOC was prepared from the leaves of O. corniculata, analyzed for total phenolic and flavonoid content, and subjected to GCMS and LC/MS-MS analyses for identification of various chemical compounds. The identified compounds were screened for antioxidant and cholinesterase inhibition potential by molecular docking analysis. In vitro antioxidant activity by free radical scavenging assay (DPPH assay), acetylcholinesterase (AChE) inhibition, and cytotoxicity in SHSY-5Y cells by MTT assay, of MEOC was evaluated. Furthermore, measurement of reactive oxygen species (ROS), NF-kB inhibition, level of glutathione, superoxide dismutase (SOD), malonaldehyde (MDA) and catalase in MEOC treated Lipopolysaccharide (LPS)-stimulated SHSY-5Y cells was also determined.

RESULTS: MEOC contained 41.22 mg of GAE/g and 82.12 mg of QE/g of MEOC of total phenolics and flavonoids, respectively. GCMS analysis revealed the presence of 48 compounds in MEOC, and LC/MS-MS analysis confirmed the presence of 18 phenolic acids and 15 flavonoids. MEOC did not show significant neurotoxicity in SHSY-5Y cells up to a dose of 1200 μg/mL but possessed prominent antioxidant and acetylcholinesterase inhibition property. MEOC significantly reduced the level of ROS, NF-kB and MDA, however, the level of glutathione, SOD and catalase increased significantly in LPS-stimulated SHSY-5Y cells. Molecular docking studies were performed against the targets 4EY7 (AChE receptor), 4TPK (butyrylcholinesterase, BuChE receptor), and 2BXK (antioxidant receptor). Among the compounds identified through GC-MS analysis, squalene exhibited the highest docking scores across all targeted proteins. In contrast, among the flavonoids identified by LC-MS, rutin showed the strongest binding affinities toward the active sites of 4EY7 and 4TPK, with LibDock scores of 144.525 and 148.499, respectively, whereas myricetin recorded the highest docking score (125.097) against 2BXK. Among the phenolic acids identified by LC-MS, chlorogenic acid exhibited the highest binding affinities for AChE and BuChE, with docking scores of 130.868 (4EY7) and 125.387 (4TPK), respectively, while ferulic acid showed the strongest binding affinity toward the antioxidant receptor 2BXK.

CONCLUSION: The findings indicate that MEOC is a rich source of phytoconstituents having antioxidant and cholinesterase inhibitory properties and may be useful in circumventing AD. It can be concluded that the leafy vegetable, O. corniculata is beneficial in AD and may be explored in the future for its mechanism of action through in vivo studies.},
}

@article {pmid41534661,
year = {2026},
author = {Costa, I and Barbosa, DJ and Remião, F and Sousa, ME and Silva, R},
title = {A dive into the untapped potential of marine compounds in counteracting neurodegeneration.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108982},
doi = {10.1016/j.pharmthera.2026.108982},
pmid = {41534661},
issn = {1879-016X},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are characterized by the progressive breakdown and eventual loss of synapses and neurons, primarily driven by the accumulation of pathologically altered proteins within the brain and spinal cord. These diseases have complex and multifactorial etiologies, involving a broad spectrum of pathophysiological mechanisms, many of which remain incompletely understood. Nonetheless, several key pathways are consistently implicated across these conditions, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. Given their rising prevalence and the persistent lack of effective disease-modifying therapies, the development of novel therapeutic strategies capable of targeting multiple pathophysiological processes is of critical importance for delaying or halting disease progression. In this context, marine natural compounds have emerged as promising candidates for counteracting neurodegeneration, owing to their ability to modulate key pathophysiological hallmarks of distinct neurodegenerative diseases. Derived from a wide range of marine organisms - including algae, sponges, fungi, and cyanobacteria - these bioactive molecules possess unique chemical structures and exhibit a broad spectrum of neuroprotective effects. Many have demonstrated potent antioxidant, anti-apoptotic, and mitochondrial-stabilizing activities in preclinical models. This review highlights recent advances in the discovery and characterization of marine-derived compounds with therapeutic potential in neurodegenerative diseases, contextualizing their pathologic mechanisms.},
}

@article {pmid41534646,
year = {2026},
author = {Liu, D and Yang, H and Feng, X and Hou, M and Fu, X and Li, X and Hong, W and Chen, L and Li, J and Ma, L and Liao, Q and Liu, Y and Lu, J and Wang, D and Zhou, H and Zhou, R},
title = {Probucol attenuates bone loss in APP/PS1 mice and ameliorates Aβ42-induced osteoblast dysfunction by regulating AKT/FOXO3a signaling pathway.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {113034},
doi = {10.1016/j.exger.2026.113034},
pmid = {41534646},
issn = {1873-6815},
abstract = {BACKGROUND: Alzheimer's disease (AD) and osteoporosis are common age-related degenerative diseases. Emerging evidence suggests that amyloid-β (Aβ) deposition may contribute to the pathogenesis of both conditions. This study investigated whether probucol could alleviate AD-associated bone loss and Aβ42-induced osteoblast dysfunction, and further explored the underlying mechanisms.

METHODS: Female mice were divided into four groups (n = 5 per group): C57BL/6 wild-type (WT), WT treated with probucol (WT + PBC), APP/PS1 transgenic (AD) mice, and AD treated with probucol (AD+PBC). Bone mineral density (BMD) was assessed by micro-CT. Levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) along with bone metabolism markers including fibroblast growth factor 23 (FGF23), sclerostin, and brain-derived neurotrophic factor (BDNF) in bone and brain tissues were measured by ELISA. FOXO3a was knocked down in the bone marrow of APP/PS1 mice via stereotactic injection of lentiviral vectors. Expression of APP and FOXO3a in bone tissue was evaluated using RT-qPCR and Western blotting (WB). Mitochondrial damage in osteoblasts and neuronal cells was assessed by transmission electron microscopy (TEM). In vitro study, osteoblast differentiation and mineralization deficits were evaluated using Alizarin Red staining. WB was used to measure the expression of AKT, FOXO3a, autophagy and apoptosis related proteins.

RESULTS: Probucol attenuated bone loss and mitochondrial damage in both APP/PS1 and FOXO3a-knockdown APP/PS1 mice, and improved cognitive impairment and neuronal ultrastructure in APP/PS1 mice. Furthermore, probucol attenuated Aβ42-induced osteoblast differentiation and mineralization via the AKT/FOXO3a signaling pathway in vitro.

CONCLUSION: These findings demonstrate that probucol ameliorates AD-associated bone loss and Aβ42-induced osteoblast impairments by regulating AKT/FOXO3a signaling pathway.},
}

@article {pmid41534360,
year = {2026},
author = {Cecchetti, G and Lanzone, J and Zanchi, L and Rugarli, G and Basaia, S and Cursi, M and Coraglia, F and Spinelli, EG and Ghirelli, A and Canu, E and Sibilla, E and Caso, F and Santangelo, R and Curti, D and Fanelli, GF and Bellini, A and Magnani, G and Agosta, F and Filippi, M},
title = {Resting-State EEG captures functional network correlates of plasma p-Tau-217 in Alzheimer's disease.},
journal = {NeuroImage. Clinical},
volume = {49},
number = {},
pages = {103947},
doi = {10.1016/j.nicl.2026.103947},
pmid = {41534360},
issn = {2213-1582},
abstract = {BACKGROUND: Scalable biomarkers are needed for early Alzheimer's disease (AD) detection. Plasma p-tau217 reflects AD pathology, while resting-state EEG captures functional brain alterations. Their relationship remains unclear.

METHODS: We enrolled 128 patients with subjective cognitive decline (SCD), mild cognitive impairment due to AD (AD-MCI), or AD dementia (AD-DEM), who underwent 32-channel EEG and plasma biomarker assessment. EEG features included spectral, aperiodic, phase-amplitude coupling, and complexity metrics. Machine learning was used to classify p-tau217 positivity.

RESULTS: AD-MCI and AD-DEM patients showed increased p-tau217 and spectral slowing (higher theta, lower alpha). While no correlations survived correction for multiple comparisons, stage-specific analyses revealed positive associations between theta power and p-tau217 in AD-MCI and AD-DEM. A random forest classifier achieved an AUC of 0.75 in predicting p-tau217 positivity.

CONCLUSIONS: EEG captures functional alterations reflecting AD pathology beyond molecular measures, supporting its value as a complementary, non-invasive biomarker for early stratification in clinical settings.},
}

@article {pmid41534330,
year = {2025},
author = {Cheng, N and Li, G and Liang, Y and Qiu, Y and Song, X and Hu, H and Tan, EL and Wang, T and Wang, S and Xiao, X and Zhao, S and Lei, B},
title = {Early Alzheimer's disease classification via structure and feature-based graph attention network from multi-center data.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {198},
number = {},
pages = {108530},
doi = {10.1016/j.neunet.2025.108530},
pmid = {41534330},
issn = {1879-2782},
abstract = {With the increasing Alzheimer's disease (AD) prevalence, morbidity, and mortality, its early diagnosis is particularly important. The multi-modal data can be used to analyze intermodal feature relationships and enhance the feature expression ability related to AD. The stable and discriminative features are obtained by fusing multiple regions of interest among different modalities. In this paper, a novel graph attention network is proposed that integrates image as well as non-image information for each subject, leveraging a structure-based, and feature-based approach. Initially, we devise a group sparse representation approach that takes into account the strength of the connections among the blood-oxygen-level-dependent (BOLD) signals in the corresponding brain regions of subjects, which constrains the correlation between brain functional networks. We utilize structural networks as a means of supervising the construction of functional networks to obtain brain networks, considering their biological significance. Then, the construction of the sparse graph involves incorporating gender and age information of the subjects with multi-center neuroimaging features. Eventually, the information on individual and common embedding is extracted from existing node features for classification. The diagnostic performance is improved by utilizing fused weight information obtained through the use of topological structure and its combination, parameter sharing, and attention mechanism. We evaluate the proposed method using both the public Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and the in-house dataset. The comprehensive experimental results indicate that our approach surpasses the conventional methods.},
}

@article {pmid41534153,
year = {2026},
author = {Lozupone, G and Bria, A and Fontanella, F and Meijer, FJA and De Stefano, C and Huisman, H},
title = {Latent diffusion autoencoders: Toward efficient and meaningful unsupervised representation learning in medical imaging - a case study on Alzheimer's disease.},
journal = {Medical image analysis},
volume = {109},
number = {},
pages = {103932},
doi = {10.1016/j.media.2026.103932},
pmid = {41534153},
issn = {1361-8423},
abstract = {This study presents Latent Diffusion Autoencoder (LDAE), a novel encoder-decoder diffusion-based framework for efficient and meaningful unsupervised learning in medical imaging, focusing on Alzheimer's disease (AD) using brain MRI from the ADNI database as a case study. Unlike conventional diffusion autoencoders operating in image space, LDAE applies the diffusion process in a compressed latent representation, improving computational efficiency and making 3D medical imaging representation learning tractable. To validate the proposed approach, we explore two key hypotheses: (i) LDAE effectively captures meaningful semantic representations on 3D brain MRI associated with AD and ageing, and (ii) LDAE achieves high-quality image generation and reconstruction while being computationally efficient. Experimental results support both hypotheses: (i) linear-probe evaluations demonstrate promising diagnostic performance for AD (AUROC: 90%, ACC: 84%) and age prediction (MAE: 4.1 years, RMSE: 5.2 years); (ii) the learned semantic representations enable attribute manipulation, yielding anatomically plausible modifications; (iii) semantic interpolation experiments show strong reconstruction of missing scans, with SSIM of 0.969 (MSE: 0.0019) for a 6-month gap. Even for longer gaps (24 months), the model maintains robust performance (SSIM > 0.93, MSE < 0.004), indicating an ability to capture temporal progression trends; (iv) compared to conventional diffusion autoencoders, LDAE significantly increases inference throughput (20 × faster) while also enhancing reconstruction quality. These findings position LDAE as a promising framework for scalable medical imaging applications, with the potential to serve as a foundation model for medical image analysis. Code is publicly available at https://github.com/GabrieleLozupone/LDAE.},
}

@article {pmid41534107,
year = {2025},
author = {Zeng, X and Deek, RA and Nafash, MN and Gu, JM and Choity, L and Lafferty, TK and Farinas, MF and Bedison, MA and Mercurio, RB and Matan, C and Gogola, A and Kofler, JK and Tudorascu, DL and Shaaban, CE and Lingler, JH and Pascoal, TA and Klunk, WE and Villemagne, VL and Ikonomovic, MD and Berman, SB and Sweet, R and Snitz, BE and Cohen, AD and Kamboh, MI and Lopez, OL and Karikari, TK},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 2},
number = {},
pages = {e106702},
doi = {10.1002/alz70856_106702},
pmid = {41534107},
issn = {1552-5279},
mesh = {Humans ; Female ; *Biomarkers/blood ; Male ; *tau Proteins/blood ; Aged ; Cross-Sectional Studies ; *Alzheimer Disease/blood/diagnosis ; *Cognitive Dysfunction/blood/diagnosis ; Glial Fibrillary Acidic Protein/blood ; Cohort Studies ; Middle Aged ; Neuropsychological Tests ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: Plasma biomarkers have demonstrated excellent performances in detecting AD/ADRD-related brain pathology. However, their relationship with cognitive decline remains unclear. We examined this in a large memory clinic cohort with baseline plasma biomarkers and repeated cognitive assessments over approximately three decades.

METHOD: Participants at the University of Pittsburgh Alzheimer's Disease Research Center underwent blood collection and Clinical Dementia Rating (CDR) Sum of Boxes-based cognitive assessment cross-sectionally, followed by annual CDR assessments for up to 29 years (3.0 [IQR 1.9-5.9]). Plasma p-tau181, p-tau217, brain-derived tau (BD-tau), GFAP and NfL, were measured using SIMOA assays. Linear/logistic regression and Fisher's exact were employed for statistical inference.

RESULT: We included 4,073 participants (59.9% female; 90.2% self-identified non-Hispanic White), aged 71.9 ± 9.8 years, with 2160 being non-demented (CDR≤0.5) at baseline. Cross-sectionally, higher levels of all biomarkers were significantly associated with worse CDR scores. Longitudinally, baseline p-tau181 and GFAP levels best predicted cognitive decline at 0-2, 2-5, 5-10, and >10 years. In contrast, p-tau217 was superior at predicting whether cognitive decline would happen at all within 2, 5, or 10 years, with AUCs up to 0.810. Participants with above-median p-tau217 levels had the highest odds of cognitive decline (2.57, 4.53, and 10.34 times within 2, 5 and 10 years, respectively). p-tau217, and p-tau217/BD-tau ratio accounting for CNS-derived p-tau217, were most effective in predicting cognitive decline in participants who were cognitively non-demented at baseline. Importantly, cognitively stable individuals had lower levels of all plasma biomarkers vs. progressors, with p-tau217 best at separating these groups.

CONCLUSION: Leveraging a large cohort with extensive longitudinal data, our findings underscore the significant value of blood-based biomarkers in predicting cognitive decline to aid personalized clinical management and ultimately improve patient outcomes.},
}

Humans
Female
*Biomarkers/blood
Male
*tau Proteins/blood
Aged
Cross-Sectional Studies
*Alzheimer Disease/blood/diagnosis
*Cognitive Dysfunction/blood/diagnosis
Glial Fibrillary Acidic Protein/blood
Cohort Studies
Middle Aged
Neuropsychological Tests
Neurofilament Proteins/blood

@article {pmid41533676,
year = {2026},
author = {Serio, G and Pacelli, C and Piccoli, C and Capitanio, N and Cibelli, G and Valenzano, AA and Landini, F and Carlucci, L and Palladino, P},
title = {Faster but less accurate: An explorative study on the effects of three weeks of ketogenic diet on cognitive functions in undergraduate students.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0338877},
doi = {10.1371/journal.pone.0338877},
pmid = {41533676},
issn = {1932-6203},
mesh = {Humans ; *Diet, Ketogenic/psychology ; *Cognition/physiology ; Female ; Male ; *Students/psychology ; Young Adult ; Adult ; Neuropsychological Tests ; Memory, Short-Term ; Universities ; Anxiety ; },
abstract = {The ketogenic diet (KD) is a low-carbohydrate diet that induces and sustains a ketosis state and minimizes somatic glucose levels. Several psychological studies have described the positive effects of ketosis on cognitive functions for a wide range of neuropsychiatric conditions (e.g., Alzheimer's disease; epilepsy), leading to greater interest in the KD today. However, the psychological and cognitive effects of inducing ketosis via diet remain unclear, especially in healthy people. From an initial pool of thirty participants, eight undergraduate students performed a cognitive assessment before (baseline) and after three weeks (follow-up) of an isocaloric ketogenic diet. Several neuropsychological measures and psychometric tests have been administered to investigate psychological chronotype, sleep quality, eating habits, anxiety and cognitive components of attention, inhibition, and memory. Non-parametric Bayesian analysis showed that the ketogenic diet affected cognitive functions. Participants performed cognitive tests faster at follow-up than at baseline, showing improvements in visual-motor cognitive and processing speed components. However, they were less accurate on working memory tasks, suggesting a decreasing performance of higher cognitive functions. Finally, no differences in anxiety levels were found between baseline and follow-up. The results could have significant implications for identifying specific cognitive models of students based on specific lifestyle habits and nutritional patterns, allowing the implementation of targeted interventions to improve university learning conditions.},
}

Humans
*Diet, Ketogenic/psychology
*Cognition/physiology
Female
Male
*Students/psychology
Young Adult
Adult
Neuropsychological Tests
Memory, Short-Term
Universities
Anxiety

@article {pmid41533472,
year = {2026},
author = {Shah, A and Kalu, U and Chen, D and Slomkowski, M and Hobart, M and Such, P and Grossberg, GT},
title = {Brexpiprazole side-effect profile in people with agitation in Alzheimer's dementia: a plain language summary.},
journal = {Current medical research and opinion},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/03007995.2025.2608578},
pmid = {41533472},
issn = {1473-4877},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SETTING: An urban university research center.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Humans
*Dementia/diagnosis/complications/psychology
*Cognition

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

Humans
*Dementia/diagnosis
Argentina
Algorithms

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

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

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

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

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

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