Journal of Alzheimer's Disease最新文献

{"title":"Greater amyloid burden in cognitive networks in preclinical Alzheimer's disease.","authors":"Sara A Nolin, Stephanie Aghamoosa, William J Rieter, Averi Jones, Paul J Nietert, Andreana Benitez","doi":"10.1177/13872877261493984","DOIUrl":"10.1177/13872877261493984","url":null,"abstract":"<p><p>BackgroundIn preclinical Alzheimer's disease (pAD), regional patterns of amyloid-β (Aβ) deposition are well characterized but have not been systematically compared across functional networks.ObjectiveDetermine how Aβ accumulation in functional networks (\"network-amyloid burden\" [NAB]) varies by age, network type (cognitive versus non-cognitive), and Aβ status (Aβ+/Aβ-), and relates to cognition.Methods157 cognitively unimpaired adults (45-84 years; n = 28 Aβ+ per neuroradiological read) underwent brain MRI, amyloid PET (¹⁸F-florbetapir), and neuropsychological testing. NAB was calculated as the mean standard uptake value ratio within 7 networks categorized as cognitive (fronto-parietal, default mode, ventral and dorsal attention, limbic) or non-cognitive (somato-motor, visual). Linear mixed models tested how NAB varies across age, networks (by type and each separately), Aβ status, and their interactions, and relationships between NAB and cognition.ResultsNAB increased with age, most prominently in fronto-parietal and default mode networks. NAB was higher in cognitive than non-cognitive networks, and this difference was more pronounced in Aβ+ individuals. NAB was not significantly associated with cognition.ConclusionsCognitive brain networks are more vulnerable to amyloid accumulation with aging and in pAD than non-cognitive networks. Cognitive NAB may be useful for early detection and as a target for intervention in pAD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493984"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136658","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":"Screening patterns for cognitive dysfunction and influencing factors analysis for referral and training rate: Experience from a health management center.","authors":"Jian Dong, Hongrui Ma, Min Deng, Rongfen Guo, Jing Zhao, Xi Chu","doi":"10.1177/13872877261490812","DOIUrl":"https://doi.org/10.1177/13872877261490812","url":null,"abstract":"<p><p>BackgroundImplementing cognition health screening, risk assessment, and early intervention for cognitive impairment-related diseases among appropriate demographics holds significant importance in China.ObjectiveThis study aims to present a cognition health management model and to explore factors influencing referral and cognition training rates for participants enrolled in a health management center.MethodsThis cohort study examined 836 cases of potential cognitive dysfunction at a health management center in China from January to October 2023. Baseline characteristics, three-month follow-up data, and clinical outcomes were recorded. Bivariate logistic regression was employed to identify predictive factors for referral and cognition training rates.ResultsIn this study, the referral and cognition training rates among participants were only 6.58% and 4.07%, respectively. The primary barriers identified were lack of awareness and accurate understanding of cognition health and training, often linked to lower levels of education. Comorbidities of cerebrovascular disease (adjusted OR: 0.277; 95%CI: 0.112-0.683, p = 0.005) and higher levels of fasting blood glucose upon admission (adjusted OR: 0.849; 95%CI: 0.746-0.955, p = 0.013) were associated with referral. A lower MoCA score on admission (adjusted OR: 0.856; 95%CI: 0.742-0.986, p = 0.032) was associated with receiving cognition training.ConclusionsTargeted educational campaigns are essential to address low awareness of cognition health, particularly among those with lower education. Moreover, considering comorbidities and biochemical markers can enhance the prediction and implementation of referral and cognition training rates.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261490812"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136845","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":"Association of stenosis and arterial remodeling with cerebral hemodynamics and cognition.","authors":"Mervin Tee, Jose Gutierrez, Jiangbo Cui, Enli Chiang, Narayanaswamy Venketasubramanian, Christopher Chen, Jan Petr, Henk J M M Mutsaerts, Saima Hilal","doi":"10.1177/13872877261494130","DOIUrl":"https://doi.org/10.1177/13872877261494130","url":null,"abstract":"<p><p>BackgroundAssociations between intracranial stenosis, arterial remodeling, cerebral hemodynamics, including cerebral blood flow (CBF) and arterial transit time (ATT), white matter hyperintensities (WMH), and cognition remain unclear.ObjectiveThis study investigates the relationships between MRA-derived vascular parameters, cerebral hemodynamics, WMH burden, and cognition. We hypothesized that greater stenosis or remodeling is associated with impaired hemodynamics, increased WMH burden, and poorer cognition.MethodsCross-sectional study of 452 memory clinic patients (median age 74 [IQR 68-78], 53% female) who underwent 3T MRI with time-of-flight MRA and pseudo-continuous ASL. Automated quantification derived global stenosis and brain arterial remodeling (BAR) scores. CBF and spatial coefficient of variation (sCoV) assessed hemodynamics; WMH volume from FLAIR; cognition from a validated neuropsychological battery. Structural equation modelling (SEM) evaluated associations, adjusting for demographics and cardiovascular risk factors.ResultsHigher sCoV was associated with higher BAR (β = 0.14, 95% CI:0.06-0.23). WMH was associated with stenosis (β = 0.20, CI:0.12-0.28) and BAR (β = 0.07, CI:0.001-0.140). Lower CBF (β = -0.26, CI:-0.36 to -0.15) and higher sCoV (β = 0.27, CI:0.17-0.36) were associated with greater WMH burden. Higher BAR was associated with better global cognition (β = 0.07, CI:0.00-0.14). SEM indicated indirect associations with cognition via WMH and CBF.ConclusionsVascular remodeling and stenosis are associated with cerebral hemodynamics, WMH, and cognition, with CBF and WMH as potential mediators, underscoring the importance of vascular health in Alzheimer's disease. These direct and indirect associations are not mutually exclusive: higher BAR was associated with better cognition directly, while also relating to poorer cognition indirectly through greater WMH burden and perfusion heterogeneity.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261494130"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136715","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":"Diabetic foot ulcers as markers of systemic disease burden: Associations with cognitive impairment in type 2 diabetes-A case-control cross-sectional study.","authors":"Niladri Dutta, Prithbijit Chatterjee, Gayatri Sreemantula, Peter Hobson","doi":"10.1177/13872877261493172","DOIUrl":"https://doi.org/10.1177/13872877261493172","url":null,"abstract":"<p><p>BackgroundType 2 diabetes mellitus (T2DM) confers increased risk of cognitive decline and Alzheimer's disease (AD), driven by chronic metabolic dysregulation, microvascular injury, and systemic inflammation. Diabetic foot ulcers (DFUs), a severe complication of T2DM, reflect advanced systemic burden, yet their neurocognitive consequences remain insufficiently characterized.ObjectiveTo evaluate domain-specific cognitive functioning in adults with DFUs compared with matched healthy controls using an AD-focused cognitive assessment battery, and to examine associations with depressive symptoms and health-related quality of life (HRQoL).MethodsIn this cross-sectional case-control study, 22 adults with T2DM and DFUs and 22 age- and gender-matched healthy controls completed the Addenbrooke's Cognitive Examination III, Trail Making Test, and Weigl Colour Form Sorting Test. Comorbidity burden, depressive symptoms (PHQ-9), and HRQoL (EQ-5D-5L) were recorded. Adjusted odds of domain-specific cognitive impairment were estimated using Generalized Linear Models.ResultsDFU participants showed significantly poorer performance across multiple cognitive domains, including verbal fluency, visuospatial ability, memory, and executive function. Independent neuropsychological tests corroborated slowed processing speed and reduced cognitive flexibility. DFU status was associated with more than a threefold increase in odds of impairment in fluency and visuospatial domains. The DFU participants also demonstrated markedly poorer HRQoL, higher depressive symptoms, and greater comorbidity burden.ConclusionsDFUs are associated with a more severe and domain-specific neurocognitive profile than typically observed in T2DM alone, affecting functions highly relevant to early AD vulnerability. These findings suggest that DFUs may identify a subgroup at heightened risk of neurodegenerative trajectories, supporting the need for biomarker-informed longitudinal investigations.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493172"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136696","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":"PET-based evaluation of short-term amyloid-β clearance and predictive factors in real-world Alzheimer's disease patients treated with lecanemab.","authors":"Zhen Qiao, Xiaobin Zhao, Guihong Wang, Shen Li, Tenghong Lian, Lin Ai","doi":"10.1177/13872877261493063","DOIUrl":"https://doi.org/10.1177/13872877261493063","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a common progressive neurodegenerative disorder. Lecanemab, an anti-amyloid-β (Aβ) monoclonal antibody, is approved for AD treatment, but real-world efficacy and optimal PET application strategies remain incompletely defined.ObjectiveTo investigate lecanemab's Aβ clearance efficacy, identify predictors of response, and optimize PET application strategies.MethodsA retrospective analysis of Aβ PET-positive AD patients treated with lecanemab for 6-8 months. Paired t-tests evaluated standardized uptake value ratios (SUVR) and cognitive changes; Cohen's Kappa assessed visual-quantitative agreement. Exploratory analyses included partial correlation, regression, and Fisher's exact test.ResultsThirty-eight patients were included. Statistically significant Centiloid (CL) reduction occurred post-treatment (mean difference = 29.39 ± 22.31, p < 0.001), without Mini-Mental State Examination/Montreal Cognitive Assessment or tau PET changes. Twelve patients achieved a CL < 24.1, and 5 were visually negative. Visual-quantitative agreement was fair to poor (positivity Kappa = 0.205; efficacy Kappa = 0.253). Baseline CL, treatment cycles, and SUVRtau were screened by univariate regression (p < 0.05) and entered into a multivariate model (F = 13.693, p < 0.001, adjusted R² = 0.507). Baseline CL (standardized-β = 0.594, p < 0.001) and treatment cycles (standardized-β = 0.285, p = 0.022) were independent positive predictors; SUVRtau showed marginal negative association (standardized-β = -0.238, p = 0.052).ConclusionsLecanemab was associated with statistically significant amyloid clearance. Baseline amyloid burden and treatment exposure predicted greater clearance; tau showed attenuating trend. Visual-quantitative discordance supports a hybrid PET pathway: visual screening for inclusivity, serial CL quantification for monitoring, and combined assessment for low-CL patients.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493063"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136831","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":"Assessing neuropsychiatric symptoms in context: Integrating standardized and ecological approaches for better care.","authors":"Ana Rita Leal Ferreira, Lia Paula Nogueira Sousa Fernandes","doi":"10.1177/13872877261491983","DOIUrl":"https://doi.org/10.1177/13872877261491983","url":null,"abstract":"<p><p>Neuropsychiatric symptoms (NPS) are common, disabling, and burdensome core features of dementia that often dominate the disease presentation and trajectory. Despite their prevalence and clinical significance, the assessment of NPS remains challenging in clinical practice. Traditional standardized assessment instruments, while widely used, are limited by their reliance on caregivers' retrospective recall, single time-point measurements, lack of direct observation, and limited ability to capture the NPS dynamic, fluctuating and context-dependent nature. A critical caveat of standardized assessment instruments lies in the insufficient exploration of NPS underlying causes, underscoring the need to refine existing approaches to better assist clinicians in detection, diagnosis, and management.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261491983"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136695","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":"Alzheimer's disease and olfactory dysfunction: A 20-year systematic bibliometric and genomic analysis.","authors":"Guohui Yang, CuiDa Meng, DongDong Zhu","doi":"10.1177/13872877261486344","DOIUrl":"https://doi.org/10.1177/13872877261486344","url":null,"abstract":"<p><p>With the acceleration of global population aging, early diagnosis and intervention of Alzheimer's disease (AD) and other neurodegenerative disorders have become major public health challenges. Olfactory dysfunction (OD) is increasingly recognized as one of the earliest clinical manifestations of AD, highlighting the importance of understanding the relationship between AD and olfactory impairment. This study integrates bibliometric analysis and genomic approaches to systematically characterize global research trends and explore potential molecular mechanisms underlying AD and OD from 2006 to 2025. Publications related to AD and OD were retrieved from the Web of Science Core Collection, and bibliometric analyses were performed using CiteSpace and VOSviewer, with results further validated through the Scopus database. A total of 1412 publications were identified, demonstrating sustained growth over the past two decades and a rapid expansion phase after 2019. The United States and China were the leading contributors in publication output and international collaboration, although research development remained geographically uneven. Keyword analysis revealed a gradual transition from behavioral and pathological investigations toward early diagnosis, biomarker discovery, therapeutic exploration, and advanced technologies. Genomic analysis identified 1838 shared genes between AD and OD, with key hub genes including AKT1, INS, and ALB involved in common biological pathways associated with neuronal function, cognitive regulation, and olfactory system homeostasis. This study provides a comprehensive overview of the evolving research landscape of AD and OD, identifies emerging trends and potential molecular targets, and offers valuable insights for early screening, mechanistic investigation, and translational research in neurodegenerative diseases.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261486344"},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127596","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":"Alterations in diacylglycerol kinase θ define early pathological features of Alzheimer's disease in a mouse model.","authors":"Marika Lanza, Rossella Basilotta, Sarah Adriana Scuderi, Pietro Giovani, Antonella Caccamo, Giovanna Casili, Salvatore Oddo, Emanuela Esposito","doi":"10.1177/13872877261490813","DOIUrl":"https://doi.org/10.1177/13872877261490813","url":null,"abstract":"<p><p>BackgroundDiacylglycerol kinase theta (DGKθ) is an enzyme involved in lipid signaling pathways and has been implicated in Alzheimer's disease (AD). DGKθ plays a crucial role in regulating diacylglycerol and phosphatidic acid levels, which are important for neuronal function and survival. Dysregulation of DGKθ leads to abnormal lipid signaling, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration-hallmarks of AD.ObjectiveThis study aimed to assess the involvement of DGKθ in AD by measuring DGKθ levels as a function of age in the brains of APP/PS1 mice and associating its changes with key AD neuropathological markers.MethodsTo investigate the role of DGK-θ in AD, brain tissues from young and aged APP/PS1 transgenic and wild-type mice were analyzed using western blot, immunohistochemistry, and Pearson correlation analyses to establish relationships between protein expression levels.ResultsWe found that DGKθ levels were higher in older, but not in younger, APP/PS1 mice compared to age-matched controls. Notably, there was a positive correlation between DGKθ levels, Aβ₄₂ levels, and astrogliosis.ConclusionsThese results suggest that DGKθ may play an important role in AD and that its modulation could represent a potential therapeutic strategy for this insidious disorder.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261490813"},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127615","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":"White matter hyperintensities moderate neuropsychiatric response to N-acetylcysteine and exercise therapy in vascular mild cognitive impairment.","authors":"Ethan Mah, Damien Gallagher, Yejin Kang, Fuqiang Gao, Joel Ramirez, Zahinoor Ismail, Sandra E Black, Xingshan Cao, Nathan Herrmann, Susan Marzolini, Paul Oh, Jinghan Jenny Chen, Kate Survilla, Walter Swardfager, Danielle Vieira, Mark J Rapoport, Krista L Lanctôt","doi":"10.1177/13872877261490542","DOIUrl":"https://doi.org/10.1177/13872877261490542","url":null,"abstract":"<p><p>BackgroundVascular mild cognitive impairment (vaMCI) is frequently accompanied by neuropsychiatric symptoms (NPS), particularly apathy, which are associated with white matter hyperintensities (WMH). N-acetylcysteine (NAC) combined with exercise may provide neuroprotective benefits.ObjectiveWe hypothesized that baseline frontal and global WMH burden would moderate the neuropsychiatric response to NAC plus exercise. We further hypothesized that the strongest domain-specific effects would be observed for apathy and affective dysregulation.MethodsParticipants with vaMCI were randomized to NAC (2400 mg daily) or placebo plus exercise for 6 months. WMH volumes were quantified using structural MRI. NPS were assessed using the Mild Behavioral Impairment Checklist (MBI-C) at baseline, 3 months, and 6 months. Negative binomial generalized linear mixed models examined WMH × time × treatment interactions. False discovery rate (FDR) correction was applied.ResultsFifty-one participants were included. Lower baseline frontal (<i>β</i> = 0.229, SE = 0.070, FDR-adjusted <i>p</i> = 0.007) and global (<i>β</i> = 0.258, SE = 0.080, FDR-adjusted <i>p</i> = 0.007) WMH volume was associated with greater reductions in NPS over 6 months in the NAC plus exercise group. This effect was driven by improvements in apathy (frontal: <i>β</i> = 0.186, SE = 0.076, FDR-adjusted <i>p</i> = 0.048; global: <i>β</i> = 0.207, SE = 0.089, FDR-adjusted <i>p</i> = 0.049).ConclusionsBaseline WMH burden moderates neuropsychiatric treatment response in vaMCI. These findings support the importance of optimizing care for cerebrovascular risk factors in this vulnerable population.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261490542"},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127603","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 between higher-order executive planning and subjective cognitive decline in middle-aged individuals.","authors":"Miguel Ramos-Henderson, Paulina Aliaga-Gallardo, Camila Aguilar-Riveros, Loreto Fuentes, Carlos Calderón, Marcos Domic-Siede","doi":"10.1177/13872877261470712","DOIUrl":"10.1177/13872877261470712","url":null,"abstract":"<p><p>BackgroundSubjective cognitive decline (SCD) is a recognized risk factor for future objective cognitive impairment and dementia. Although widely studied in older adults, SCD during midlife remains underexplored, despite this period representing a critical window for early detection. Higher-order executive functions, particularly cognitive planning, may be especially sensitive to subtle cognitive changes at this stage.ObjectiveTo examine the association between higher-order executive function performance and subjective cognitive decline in middle-aged individuals.MethodsThis cross-sectional study included 167 community-dwelling middle-aged adults (45-60 years) with SCD and normal global cognition. Participants completed the Subjective Cognitive Decline Questionnaire (SCDq), mood and sleepiness measures, structured executive function tests, and the Zoo Map Test (ZMT) to assess higher-order executive planning. Group comparisons, correlation analyses, and hierarchical linear regressions were performed.ResultsHigher SCD levels were associated with longer planning times and more planning errors on the ZMT. No associations were observed between SCD and global cognitive performance or structured executive function measures. In the hierarchical regression model, mood symptoms and daytime sleepiness explained 23% of SCD variance, while higher-order executive planning measures accounted for an additional 8.4%, yielding a final hierarchical model explaining 33.6% of the variance. Fully adjusted simultaneous model showed the same pattern.ConclusionsSCD in midlife is associated with subtle differences in higher-order executive functioning that emerge under high cognitive demand. Ecologically valid executive tasks may improve early detection of individuals at risk for future objective cognitive decline beyond traditional neuropsychological measures.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"1084-1098"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549124","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}