Journal of Alzheimer's Disease最新文献

{"title":"Decreased cerebrospinal fluid NDRG2 is associated with non-Alzheimer's disease derived mild cognitive impairment.","authors":"Qing-Ning Zhang, Wei Wu, Yong-Ming Zhou, Lan-Ke Yu, Xin-Yuan Zhang, Jia-Lin Wu, Si-Yuan Song, Zhao-Hui Yao","doi":"10.1177/13872877261477113","DOIUrl":"10.1177/13872877261477113","url":null,"abstract":"<p><p>BackgroundMild cognitive impairment (MCI) lacks clear clinical biomarkers. N-Myc downstream-regulated gene 2 (NDRG2) is predominantly localized in astrocytes and is implicated in cognitive function.ObjectiveThis study aims to explore whether cerebrospinal fluid (CSF) NDRG2 could predict MCI and investigate its underlying mechanisms of cognitive decline.MethodsA total of 650 CSF samples were collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, comprising 157 normal individuals, 366 MCI patients, and 127 Alzheimer's disease (AD) patients. One-way analysis of covariance (ANCOVA) was employed to assess differences in CSF NDRG2 levels among groups. Linear regression was used to analyze the correlation between NDRG2 and amyloid-β (Aβ), phosphorylated tau (p-tau), ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET), albumin quotient (Qalb), and growth-associated protein 43 (GAP43). Receiver operating characteristic (ROC) curves were used to examine the diagnostic performance of NDRG2 for MCI.ResultsCSF NDRG2 levels were significantly reduced in MCI, most prominently in non-Aβ and non-tau subgroups. NDRG2 discriminated Aβ-negative MCI with an area under the curve (AUC) of 0.719, but showed limited discriminatory capacity in Aβ+, tau+, and apolipoprotein E ε4 (<i>APOE</i> ε4) carrier groups. Furthermore, CSF NDRG2 levels were positively correlated with GAP-43, a marker of synaptic plasticity.ConclusionsThe present study demonstrates that NDRG2 is a potential biomarker for non-AD derived MCI and suggests its involvement in synaptic plasticity impairment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261477113"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of television viewing, computer use, and Alzheimer's disease among United States adults: A cross-sectional study of NHANES.","authors":"Bei Li, Jie Han, Meidi Yang, Wen Yang, Lihui Wang","doi":"10.1177/13872877261476960","DOIUrl":"10.1177/13872877261476960","url":null,"abstract":"<p><p>BackgroundElectronic screen use has become increasingly prevalent in modern society; however, its relationship with Alzheimer's disease (AD) remains unclear and insufficiently characterized.ObjectiveTo examine the associations of television (TV) viewing time and computer use with AD among United States (U.S.) adults.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2011-2016. A total of 12,165 participants aged ≥45 years were included. Survey-weighted logistic regression models were used to evaluate the associations between screen time and AD. Restricted cubic spline (RCS) analyses were performed to explore potential nonlinear relationships.ResultsLonger TV viewing time was significantly associated with higher odds of AD (OR 1.18, 95% CI: 1.08-1.29, <i>p_FDR</i> = 0.002). Computer use was not significantly associated with AD in the main models. RCS analyses showed that computer use had a significant nonlinear U-shaped association with AD (<i>p</i> for nonlinear <0.001), with the lowest odds observed at approximately two hours per day.ConclusionsAmong U.S. adults aged ≥45 years, longer TV viewing time was associated with higher odds of AD, whereas computer use showed a nonlinear association with the lowest odds observed at around two hours per day.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476960"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAIN-Diabetes: Acceptability of an adapted FINGER multidomain intervention among adults living with type 2 diabetes in rural border regions across the island of Ireland.","authors":"Rebecca F Townsend, Lesley L Hamill, Dominic N Farsi, Geraldine McCarthy, Catherine Dolan, Bernadette McGuinness, Sean P Kennelly, Joanne Regan-Moriarty, Frank Kee, Peter Passmore, Jayne V Woodside, Claire T McEvoy","doi":"10.1177/13872877261471915","DOIUrl":"10.1177/13872877261471915","url":null,"abstract":"<p><p>BackgroundIndividuals with type 2 diabetes mellitus (T2DM) face increased risk of cognitive decline and dementia. Multidomain lifestyle interventions offer a non-pharmacological strategy to support brain health in this high-risk group.ObjectiveThis study examined the acceptability of a culturally adapted FINGER-based intervention among adults living with T2DM in rural border regions of Ireland (BRAIN-Diabetes Trial).MethodsA 6-month pilot randomized controlled trial was conducted. The intervention group received a multidomain program targeting diet, physical activity, and computerized cognitive training (CCT). The control group received standard care. Acceptability was assessed using questionnaires (all participants) and semi-structured interviews (intervention participants). Quantitative data were analyzed descriptively and qualitative data using template analysis, guided by four a-priori themes: trial participation and engagement, dietary behavior change, exercise behavior change, and CCT behavior change.ResultsQuestionnaire data (intervention: n = 28; control: n = 36) indicated high overall acceptability. Dietary and exercise components were rated most positively, while CCT component was less well received. Interviews (n = 25) highlighted facilitators to trial engagement, including perceived health improvements, and social connection, with time constraints and limited personalization as barriers. Dietary change was supported by tailored guidance but hindered by cost and availability. Facilitators for exercise included accessible resources and perceived benefits, with barriers including competing priorities. CCT engagement was mixed, with challenges including digital access and repetitiveness.ConclusionsThe Brain-Diabetes intervention was acceptable and feasible among adults with T2DM. Personalized support and accessible resources were key to engagement. Future work should refine delivery to enhance scalability and long-term adherence among high-risk groups.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261471915"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an amyloid PET dementia of the Alzheimer's type (DAT) score.","authors":"Mitchell Edema, Karteek Popuri, Hyunwoo Lee, Lei Wang, Mirza Faisal Beg","doi":"10.1177/13872877261476273","DOIUrl":"10.1177/13872877261476273","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) can be debilitating if left untreated, but its progression may be altered through early detection.ObjectiveTo develop and evaluate a convolutional neural network (CNN) for detecting AD from amyloid PET brain images and to investigate the regions contributing to model predictions.MethodsA 3D CNN with residual connections was developed to classify amyloid PET brain volumes. Amyloid PET data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with approximately 600 images from cognitively normal control (NC) and dementia of the Alzheimer's type (DAT) participants used for training, validation, and testing. Performance was assessed using repeated 5-fold cross-validation (10 total folds). The model was also evaluated across the AD continuum, including unstable normal control (uNC), progressive normal control (pNC), stable mild cognitive impairment (sMCI), progressive mild cognitive impairment (pMCI), and early DAT (eDAT). Saliency and class activation maps were generated to identify regions contributing to predictions.ResultsThe model achieved a mean testing accuracy of 92% across the 10 folds. Across the disease continuum, accuracies were 76% for uNC, 78% for sMCI, 24% for pNC, 65% for pMCI, and 78% for eDAT. Saliency and class activation maps highlighted the putamen, thalamus, hippocampus, corpus callosum, and posterior cingulate cortex, regions previously implicated in AD pathology.ConclusionsThe proposed 3D CNN accurately distinguished DAT from cognitively normal controls using amyloid PET imaging and showed promising performance across the AD continuum. Model interpretation identified biologically relevant brain regions, supporting the potential of deep learning for early AD detection and clinical decision support.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476273"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bypassing the bottleneck: Gamma-glutamylcysteine supplementation for brain glutathione enrichment in Alzheimer's disease.","authors":"Pravat K Mandal, George Perry, Joseph C Maroon, Patricia Corby, Riddhi Patira, Oscar L Lopez","doi":"10.1177/13872877261474009","DOIUrl":"10.1177/13872877261474009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a major neurodegenerative disorder affecting more than 7 million Americans. Extensive studies have identified various factors associated with the development of AD, but the actual cause remains unknown. Transgenic mouse model and human studies strongly indicate that oxidative stress precedes amyloid-β plaque formation and tau phosphorylation in AD. GSH loss itself raises the Abeta42/Abeta40 ratio and promotes tau aggregation [5], placing GSH depletion upstream of classical AD pathology. Subsequently, the role of the master antioxidant, glutathione (GSH), came into focus for brain GSH level enrichment through supplementation with γ-glutamylcysteine (GGC), the immediate precursor of GSH. We present that GGC has an excellent safety record and bioavailability. GGC is a strong candidate to investigate for brain GSH enrichment (target engagement hippocampus, anterior cingulate cortex etc.) and subsequent cognitive enhancement for patients with mild cognitive impairment (MCI).</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261474009"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental illness among persons with and without dementia in continuing care: A multi-jurisdictional, repeated cross-sectional study.","authors":"Joey Champigny, David B Hogan, Ruth Ann Marrie, Jin Luo, Xueyi Chen, Okechukwu Ekuma, Randy Walld, Erind Dvorani, James M Bolton, Zahra Goodarzi, Ping Li, Dallas Seitz, Andrea Gruneir, Matthias Hoben, Nathan Herrmann, Luke Mondor, Colleen J Maxwell","doi":"10.1177/13872877261476238","DOIUrl":"10.1177/13872877261476238","url":null,"abstract":"<p><p>BackgroundLimited epidemiologic data exists for mental illnesses among at-risk home care (HC) and residential long-term care (LTC) recipients.ObjectiveTo estimate the annual prevalence (April 1, 2012-March 31, 2023) of various mental illnesses among HC and LTC populations (versus matched comparators) with and without dementia in the Canadian provinces of Ontario, Alberta, and Manitoba.MethodsParallel repeated cross-sectional studies were conducted in each province using linked health administrative data. HC and LTC recipients aged ≥18 years were matched to comparators on demographics, dementia and comorbidity. Prevalence estimates were derived using validated case definitions for any mental illness, mood/anxiety disorders, depression and anxiety (with/without drug claims), schizophrenia, bipolar disorder and suicide attempt. Prevalence ratios (95% CIs) were estimated with modified Poisson regression models.ResultsIncluded were 682,466 HC clients and 233,499 LTC residents. Mental illnesses were common in HC and LTC settings across all three provinces. Prevalence estimates were typically higher among care recipients versus matched comparators and among persons with versus without dementia. Up to 70% of HC clients and 80% of LTC residents with dementia had any mental illness; in both settings, 40% had mood/anxiety disorders, 4% bipolar disorders, and between 2%-6% schizophrenia. Suicide attempts were rare (0.5-0.6%). Prevalence varied by province and was higher for case algorithms including drug claims.ConclusionsThe high prevalence of mental illness and its common co-occurrence with dementia in HC and LTC recipients illustrates the complexity and challenges of care in these populations and raises concerns about potential unmet mental health needs.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476238"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence from European ancestry genome-wide association studies and a case-control study suggests several selenoproteins are linked to a decreased risk of Alzheimer's disease.","authors":"Peixin Jiang, Sibo Peng, Yanling Huang, Leyi Wang, Yufei Lan, Yang Li, Chenyang Wang, Cailing Feng, Haiting Xie, Leiyuan Liu, Hongbo Guo, Xiaoya Gao","doi":"10.1177/13872877261476713","DOIUrl":"10.1177/13872877261476713","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder resulting from a complex interplay of multiple factors. Recent hypotheses suggest a potential role of selenium and selenoproteins in AD pathogenesis. However, the causality relationship between them remains to be elucidated.ObjectiveThis study investigates the causal link between selenoproteins and AD risk.MethodsWe analyzed the data by leveraging genome-wide association studies from European cohorts (90,338 AD patients and 1,036,225 controls) and expression quantitative trait loci (eQTLs) from eQTLGen (31,684 individuals) and GTEx v8 (838 individuals). Mendelian randomization and summary data-based Mendelian randomization were applied to assess the potential causal associations between selenoproteins and AD. To further confirm these genetic associations at the clinical level, we conducted a case-control study to evaluate the levels of four differentially expressed selenoproteins in peripheral blood in individuals with AD and cognitively normal controls.ResultsOur analysis revealed that four selenoproteins, including selenoprotein S (SEPH2) and selenoprotein M (SELENOM), glutathione peroxidase 4 (GPX4) and thioredoxin reductase 2 (TXNRD2), were correlated with a decreased risk of AD. The levels of GPX4, SELENOM, and TXNRD2 were found to be significantly downregulated in AD patients compared to controls in the case-control validation study, supporting the change identified in our genetic analysis.ConclusionsThis study provides genetic and clinical evidence that specific selenoproteins are associated with a decreased risk of AD. The findings highlight the potential role of these proteins in AD pathophysiology and suggest their promise as biomarkers or therapeutic targets, warranting further investigation.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476713"},"PeriodicalIF":3.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression from mild cognitive impairment to dementia in Alzheimer's disease: Whole cortex voxelwise functional connectivity analysis with multivariate distance matrix regression.","authors":"Luiz Kobuti Ferreira, Eric Westman, Lars-Olof Wahlund, Rosaleena Mohanty","doi":"10.1177/13872877261477016","DOIUrl":"10.1177/13872877261477016","url":null,"abstract":"<p><p>BackgroundDifferentiating individuals with mild cognitive impairment who convert to dementia due to Alzheimer's disease (MCI-C) from those who do not convert (MCI-NC) is increasingly important. Functional connectivity (FC) derived from resting state functional MRI (rs-fMRI) has been investigated as a potential biomarker. However, improved data analysis strategies are needed. One underexplored approach is pairwise voxel-to-voxel analysis.ObjectiveTo describe differences in FC between amyloid positive MCI-C and MCI-NC using a whole-cortex voxel-to-voxel pairwise approach.MethodsBaseline rs-fMRI from the Alzheimer's Disease Neuroimaging Initiative was retrieved for amyloid positive MCI participants. Voxel-to-voxel, pairwise, cortical FC was computed. Multivariate distance matrix regression was used to identify voxels presenting FC patterns that were significantly different between MCI-C and MCI-NC.Results21 MCI-C and 28 MCI-NC were included. The primary analysis with voxel-level threshold at p < 0.001 combined with cluster-level p < 0.05 yielded no significant results. At voxel-level p < 0.01 and the same cluster-level threshold, three significant clusters on the right visual cortex were found. These clusters, however, were not robust to head motion, fMRI protocol and additionally clinical or biological severity.ConclusionsProgression from Alzheimer-related MCI to dementia was not significantly associated with FC in the primary analysis. However, a less stringent threshold yielded FC differences in the occipital lobe in alignment with previous studies but were not robust to methodological and biological covariates between groups. Our findings highlight the need for larger samples and careful control of covariates to identify robust FC alterations related to dementia conversion.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261477016"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation analysis between complement proteins and Alzheimer's disease.","authors":"Ying-Tong Lu, Zi-Ming Guo, Meng-Yuan Liu, Cheng-Hong Ji, Yu-Ting Luo, Shu-Yun Zhou, Tao Ma, Xi-Chen Zhu","doi":"10.1177/13872877261475358","DOIUrl":"10.1177/13872877261475358","url":null,"abstract":"<p><p>BackgroundThe prominent pathological features of Alzheimer's disease (AD) are amyloid-β (Aβ) plaques and tau pathology. The complement cascade is closely related to AD-associated pathological processes; however, the precise mechanisms underlying its contributions remain incompletely elucidated.ObjectiveWe aim to investigate the changes in complement protein expression during AD progression.MethodsThis study enrolled 285 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were classified into biomarker-defined groups based on predefined cutoff values for Aβ₄₂ and phosphorylated tau (P-tau). We compared cerebrospinal fluid (CSF) levels of complement proteins (C1q, C2, C3, C4a, C5, C6, C8b, and factor B) across these subgroups. Furthermore, we explored their associations with core AD biomarkers (Aβ₄₂, P-tau, and T-tau) and clinical characteristics. Additionally, we investigated age-related changes in complement gene expression within the cerebral cortex of 3xTg mice using single-nucleus RNA sequencing.ResultsComplement protein levels in the CSF of A + subjects were significantly lower than those in A- subjects, and complement protein levels were positively correlated with Aβ pathology. Complement protein levels were influenced by factors such as age, gender, body mass index, <i>APOE</i> genotype, and hypertension. Compared with control mice, the complement gene C1qa in microglia was upregulated throughout the entire pathological cycle in 3xTg AD mice.ConclusionsComplement proteins undergo significant changes during the pathogenesis of AD, and alterations in their levels may reflect early pathological changes in AD and warrant further investigation. Notably, our findings suggest that microglia may contribute to complement-mediated pathological processes associated with AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261475358"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of previous parity in the relationship between lifetime physical activity and later life cognition: The Rancho Bernardo study.","authors":"Vanja Petrović, Emilie T Reas, Raylene A Reimer, Cindy K Barha","doi":"10.1177/13872877261477010","DOIUrl":"10.1177/13872877261477010","url":null,"abstract":"<p><p>BackgroundParity history influences dementia risk and cognitive aging, and recent evidence suggests it may also influence the association between physical activity and cognition in later life.ObjectiveTo examine associations between total lifetime and life-stage-specific physical activity and later life cognition in postmenopausal females with differing parity histories.MethodsThis cross-sectional analysis using data from the Rancho Bernardo Study included 867 postmenopausal females with complete data, categorized into three parity groups (number of pregnancies >6-months): nulliparous, 1-2 pregnancies, and grand-multiparous (≥3 pregnancies). Cognitive outcomes included executive functions and memory. Physical activity was assessed using a self-report questionnaire capturing retrospective activity during adolescence, age 30, age 50, and current activity in later life. Covariates included age, education, health composite score, body mass index, and hysterectomy status. Linear models examined associations between physical activity and domain-specific later life cognitive outcomes stratified by parity.ResultsGreater total lifetime physical activity was associated with higher executive functions in nulliparous and grand-multiparous females. Moderate activity in nulliparous females and high activity in grand-multiparous females during adolescence and at age 30 were associated with higher executive functions. High physical activity at age 50 and currently was associated with higher executive functions in nulliparous females.ConclusionsThe findings suggest the relationship between self-reported physical activity and cognition was strongest in the two groups at greater risk for cognitive decline and Alzheimer's disease, the nulliparous and grand-multiparous groups. Further research is needed to understand the mechanisms driving parity differences.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261477010"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}