The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Tau-ing and fro-ing: the tanycytic shuttle in neurodegeneration.","authors":"Vincent Prévot, Markus Schwaninger, Ruben Nogueiras, S Rasika","doi":"10.1016/j.tjpad.2026.100643","DOIUrl":"10.1016/j.tjpad.2026.100643","url":null,"abstract":"<p><p>After more than a century since Alzheimer's disease (AD) was described and decades of research into β-amyloid and Tau proteins, mechanisms underlying pathogenic protein clearance from brain remain poorly understood. Recent research identifies tanycytes-specialized hypothalamic cells lining the third ventricle-as a previously unrecognized clearance system for brain Tau. These cells actively transport Tau from cerebrospinal fluid to blood via pituitary portal circulation but are dramatically fragmented in AD brains. Single-nucleus RNA sequencing reveals altered stress and transport gene expression in AD tanycytes, while functional studies show disrupted tanycytic transport reduces Tau efflux and exacerbates pathology. Beyond protein clearance, tanycytes maintain critical metabolic and neuroendocrine pathways influencing cognition. Their unique blood-brain interface position makes them attractive therapeutic targets. As transcriptomic evidence suggests tanycytes are hotspots for age-related changes, their dysfunction may herald \"tanycytopathies\" underlying multiple neurodegenerative disorders.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100643"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The generalizability gap: anticoagulant exclusions and the \"Enhanced Safety\" of donanemab in the EU-eligible population.","authors":"Azan Ijaz, Ghulam Mohyudin","doi":"10.1016/j.tjpad.2026.100628","DOIUrl":"10.1016/j.tjpad.2026.100628","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100628"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIND GamePack: A novel digital health technology for assessment of participants with and without cognitive impairment.","authors":"Jake A Galler, Liuqing Yang, Chao-Yi Wu, Cathrine Young, Edmarie Guzmán-Vélez, Katherine W Cropp, Anthony W Bannon, Hiroko H Dodge, Jessica A Gerber, Steven E Arnold","doi":"10.1016/j.tjpad.2026.100642","DOIUrl":"10.1016/j.tjpad.2026.100642","url":null,"abstract":"<p><strong>Background: </strong>Digital biomarkers offer promising avenues for enhancing the identification, prognosis, and phenotyping of Alzheimer's Disease (AD). This study evaluates the feasibility and utility of the MIND GamePack©, a digital game platform designed to measure leisure cognitive activity over time.</p><p><strong>Methods: </strong>Gameplay data were collected from 60 participants across two cohorts over 3-6 months: Cohort I (no cognitive complaints) and Cohort II (subjective complaints, mild cognitive impairment, mild dementia). Analyses focused on compliance, correlation with validated neuropsychological instruments (Montreal Cognitive Assessment [MoCA], Repeatable Battery for the Assessment of Neuropsychological Status [RBANS], and Trail Making Test [TMT]), test-retest reliability, and known groups comparison.</p><p><strong>Results: </strong>The MIND GamePack© displayed high compliance and excellent test-retest reliability within 1 week (ICC=0.81-0.95) for most selected features. Several game features displayed moderate to strong correlations with standardized neuropsychological test performance. Features related to memory tasks across select games (Normalized Accuracy and Normalized Redundant Move Variability of Memory Match and Word Repetition Rate of Word Scramble) exhibited significant associations with RBANS Sum of Index Score, TMT Part A, and MoCA, respectively. Participants without cognitive impairment exhibited improvement in features over 3 months compared to those with cognitive impairment. Baseline game features differentiated cognitively normal [CN] from cognitively impaired [CI] participants across nearly all domains after controlling for age, sex, and education (p<.01).</p><p><strong>Conclusions: </strong>The MIND GamePack© offers a sensitive, engaging approach to cognitive monitoring and screening, with potential use for dense tracking in longitudinal research and interventional clinical trials.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100642"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal asymmetry captures non-amyloid-related risk of memory decline and clinical progression.","authors":"Elham Ghanbarian, Babak Khorsand, Lukai Zheng, Davis C Woodworth, Crystal M Glover, Maria M Corrada, S Ahmad Sajjadi, Joshua D Grill, Ali Ezzati","doi":"10.1016/j.tjpad.2026.100638","DOIUrl":"10.1016/j.tjpad.2026.100638","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hippocampal atrophy is a key marker of Alzheimer's disease (AD)- related neurodegeneration; however, hippocampal volume alone may not fully capture heterogeneity in cognitive decline. Left-right hippocampal asymmetry may provide complementary information, but its prognostic value for long-term cognitive decline, particularly in relation to AD pathology, remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To determine whether hippocampal total volume and left-right hippocampal asymmetry provide complementary and independent information in capturing cognitive decline and clinical progression, and to examine their relationship to AD pathology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Analysis of baseline MRI and longitudinal cognitive data over 10 years in four domains of memory, language, executive, and visuospatial function, using harmonized cognitive data from the Alzheimer's Disease Sequencing Project - Phenotype Harmonization Consortium (ADSP-PHC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Participants from ADNI 1, ADNI GO, ADNI 2, and ADNI 3 PARTICIPANTS: A total of 1,142 dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available baseline structural MRI, cerebrospinal fluid (CSF) amyloid-β (Aβ42) and phosphorylated tau (p-tau-181), and longitudinal cognitive follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;Total hippocampal volume (left + right) and hemispheric asymmetry (absolute left-right volumetric difference) were modeled simultaneously. Linear mixed-effects models examined associations with baseline performance and longitudinal change across four cognitive domains. Cox proportional hazards models assessed risk of clinical progression to clinical dementia over up to 10 years of follow-up (median follow-up 4 years; median 5 visits per participant). All analyses adjusted for age, sex, education, APOE ε4 status, and CSF biomarkers, with stratification by amyloid status.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study cohort included 546 women (47.8%), with a mean age of 72.54 ± 6.98 years. Smaller total hippocampal volume was consistently associated with worse baseline performance and faster decline across all four cognitive domains, even after adjustment for amyloid and tau. In contrast, greater left-right hippocampal asymmetry was selectively associated with worse performance and faster decline in memory, independent of total hippocampal volume. In amyloid-stratified analyses, total hippocampal volume showed broad associations with cognitive performance across multiple domains in both amyloid-positive and amyloid-negative participants, whereas hippocampal left-right asymmetry demonstrated selective associations with memory performance, which were observed only among amyloid-negative individuals. With respect to clinical progression to dementia, smaller total hippocampal volume was associated with a higher risk of progression in the overall cohort and within both amyloid groups. In contrast, h","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100638"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary patterns for cognitive health: bridging evidence across east and west.","authors":"Lei Feng","doi":"10.1016/j.tjpad.2026.100663","DOIUrl":"10.1016/j.tjpad.2026.100663","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100663"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined effect of anxiety disorder and insomnia on the risk of incident ADRD diagnosis.","authors":"SangNam Ahn, Joanne Salas, Jinmyoung Cho, Jeffrey F Scherrer","doi":"10.1016/j.tjpad.2026.100621","DOIUrl":"10.1016/j.tjpad.2026.100621","url":null,"abstract":"<p><strong>Background: </strong>Anxiety disorders and insomnia are common modifiable conditions in older adults, but their independent and combined effects on the risk of incident Alzheimer's disease and related dementias (ADRD) remain unclear.</p><p><strong>Objectives: </strong>To estimate the independent and combined associations of anxiety disorders and insomnia with the risk of incident ADRD.</p><p><strong>Design: </strong>Retrospective cohort study using an intention-to-treat approach with a 10-year follow-up period (2014-2023).</p><p><strong>Setting: </strong>De-identified electronic health record (EHR) data from 70 participating healthcare organizations within the TriNetX Research Network.</p><p><strong>Participants: </strong>Adults aged ≥50 years without prior dementia who had regular ambulatory care during a three-year baseline period (n = 1,868,790).</p><p><strong>Measurements: </strong>Anxiety and insomnia were identified using ICD-based algorithms and categorized into four exposure groups: neither condition, anxiety only, insomnia only, and both. Incident ADRD was defined by two or more diagnostic codes within 12 months. Entropy balancing controlled for confounding, and weighted Cox proportional hazards models estimated hazard ratios (HRs).</p><p><strong>Results: </strong>At baseline, 4.1% had anxiety only, 3.8% had insomnia only, and 1.1% had both. Over follow-up, 2.3% developed ADRD. In weighted models, insomnia alone (HR: 1.12; 95% CI: 1.06-1.19), anxiety alone (HR: 1.49; 95% CI: 1.39-1.60), and co-occurring anxiety and insomnia (HR: 1.31; 95% CI: 1.06-1.62) were each associated with higher ADRD risk compared with neither condition. No significant effect modification by age, sex, or race was observed.</p><p><strong>Conclusions: </strong>Anxiety and insomnia independently increase ADRD risk, though insomnia's contribution is very modest compared to the primary association demonstrated by anxiety. Co-occurrence does not confer additional risk beyond anxiety alone. Clinically, routine screening and treatment of anxiety and sleep disturbances represent actionable, broadly applicable strategies for ADRD prevention and healthy cognitive aging.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100621"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148195062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary patterns and Alzheimer's disease: East-west perspectives and future intervention strategies.","authors":"Wanlu Jiang, Yijia Lin, Qihao Guo, Ya Miao","doi":"10.1016/j.tjpad.2026.100636","DOIUrl":"10.1016/j.tjpad.2026.100636","url":null,"abstract":"<p><p>Among various modifiable risk factors, dietary patterns (DPs), as a holistic lifestyle intervention, have become a focus of current research due to their protective effects on cognitive health. Classic Western DPs, such as the Mediterranean diet (MedDiet), have been widely confirmed to effectively improve cognitive function, thereby reducing the risk of Alzheimer's disease (AD). However, existing evidence mainly concentrates on Western populations and their DPs, including the MODERN (Machine learning-assisted Optimizing Dietary intERvention against demeNtia risk) diet optimized using machine learning. Given the significant differences in food types, dietary habits, and cooking methods among Asian populations, research on localized DPs optimized for cognitive health in Asian populations remains insufficient. In this context, the team at the Department of Geriatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine has taken the lead in systematically defining the Shanghai Cognitive Diet Pattern (SCDP). This review aims to comprehensively outline the core features and potential biological mechanisms relevant to AD in both classic Western DPs and the emerging East Asian DP. Subsequently, this review will systematically compare Eastern and Western DPs. In conclusion, this review proposes shifting​ dietary strategies from population-level adaptation to individual precision, in conjunction with multimodal lifestyle management, and offers novel strategies for the prevention and management of AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100636"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of accelerometer-measured physical activity on the association between atrial fibrillation and risk of dementia.","authors":"Le Li, Mengtong Xu, Lingmin Wu, Zhicheng Hu, Limin Liu, Likun Zhou, Minghao Zhao, Yulong Xiong, Zhenhao Zhang, Lihui Zheng, Ligang Ding, Yan Yao","doi":"10.1016/j.tjpad.2026.100603","DOIUrl":"10.1016/j.tjpad.2026.100603","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) independently increases dementia risk, but whether accelerometer-measured physical activity (PA) modifies this association remains unquantified, particularly against self-reported PA limitations.</p><p><strong>Methods: </strong>Prospective analysis of 91,795 UK Biobank participants with valid accelerometer data (median age 57, 42.9 % male; 2800 with baseline AF). We categorized whether measured activity met the standard recommendation [moderate-to-vigorous physical activity (MVPA) >_150 min/week]. Questionnaire-derived MVPA data from 353,643 UK Biobank participants (median age 57, male: 46.7 %) between 2006 and 2010 were used for validation. The primary outcome was the diagnosis of incident all-cause dementia. We also assessed correlation between accelerometer-derived and self-reported activity.</p><p><strong>Results: </strong>Over 7.6-year median follow-up, AF was significantly associated with a higher dementia risk [Adjusted hazard ratio (aHR): 1.76, 95 % confidential interval (CI): 1.51-2.05]. Guideline-adherent PA was associated with a lower AF-related dementia risk to non-significance (aHR: 1.36, 95 %CI: 0.96-1.91). Moreover, PA may be associated with higher protection effect on dementia risk in AF patients (aHR: 0.55, 95 % CI: 0.33-0.92) than in non-AF (aHR: 0.81, 95 % CI: 0.69-0.96), although without statistical difference (Pinteraction = 0.213). Correlation between accelerometer-derived and selfreported MVPA was weak (Spearman r = 0.155, 95 % CI: 0.148-0.162). Self-reported activity was not associated with a decreased risk of dementia in both AF and non-AF participants.</p><p><strong>Conclusion: </strong>Higher accelerometer-measured PA is associated with lower AF-associated dementia risk. Future prospective studies with extended follow-up and serial activity monitoring are needed to confirm these findings.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100603"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13213870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stages of objective memory impairment (SOMI) as a predictor of clinical progression in the A4 study.","authors":"Priyanka Kumari, Richard B Lipton, Andrew J Aschenbrenner, Reisa Sperling, Michael C Donohue, Ellen Grober","doi":"10.1016/j.tjpad.2026.100641","DOIUrl":"10.1016/j.tjpad.2026.100641","url":null,"abstract":"<p><strong>Background: </strong>About one third of amyloid positive, cognitively normal individuals develop mild cognitive impairment or clinical Alzheimer dementia (AD) over 5 years of follow-up. Sensitive cognitive measures, in addition to biomarkers of amyloid pathology, add to the efficiency of secondary prevention trials by identifying cognitively normal individuals at greatest risk of clinical progression. The Stages of Objective Memory Impairment (SOMI) system, based on the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR), predicted clinical progression in two observational studies.</p><p><strong>Objective: </strong>Our objective was to extend SOMI's findings to clinical trials using participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's(A4) study.</p><p><strong>Methods: </strong>Eligible participants were cognitively normal, had a Clinical Dementia Rating (CDR) =0, an elevated amyloid level, the pFCSRT+IR, pTau217, and longitudinal data on the CDR. Cox proportional hazards model was used to assess the association of baseline SOMI stage for clinical progression defined by time to the first of 2 consecutive CDRs > 0 or CDR>0 at last assessment. The sample was censored at 4.5 years of follow-up.</p><p><strong>Results: </strong>Of the 911 eligible participants, mean age was 72 years, 59% were female, 62% were APOE ε4 carriers, and 37% progressed over 4.5 years. Hazard ratios (HR) for progression were estimated with follow-up time as the timescale and the SOMI 0 group as the reference. The HRs for progression across SOMI stage increased from 1.48(1.15-1.92 p=.003) for SOMI-1, to 1.83 (1.32-2.54, p ≤ 0.001) for SOMI-2, and to 3.04 (1.97-4.68, p ≤ 0.001) for SOMI 3/4. SOMI remained an independent and significant predictor when pTau217 was added to the model.</p><p><strong>Conclusion: </strong>SOMI's risk profile in A4 was similar to prior findings in observational cohorts. SOMI provides a low-cost, non-invasive enrichment tool for identifying individuals at risk for early cognitive decline in secondary prevention trials.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100641"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subjective cognition trajectories, Alzheimer biomarkers, and incident mild cognitive impairment.","authors":"Elizabeth Kuhn, Luca Kleineidam, Melina Stark, Oliver Peters, Julian Hellmann-Regen, Lukas Preis, Daria Gref, Josef Priller, Eike Jakob Spruth, Maria Gemenetzi, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Claudia Bartels, Niels Hansen, Ayda Rostamzadeh, Emrah Düzel, Wenzel Glanz, Enise Incesoy, Katharina Buerger, Daniel Janowitz, Sophia Stöcklein, Robert Perneczky, Boris-Stephan Rauchmann, Stefan J Teipel, Ingo Kilimann, Christoph Laske, Sebastian Sodenkamp, Annika Spottke, Marie Kronmüller, Sandra Roeske, Frederic Brosseron, Alfredo Ramirez, Matthis Synofzik, Matthias C Schmid, Frank Jessen, Michael Wagner","doi":"10.1016/j.tjpad.2026.100609","DOIUrl":"10.1016/j.tjpad.2026.100609","url":null,"abstract":"<p><strong>Background: </strong>Subjective cognitive decline is common in older adults and may represent an early clinical signal along the Alzheimer's disease continuum. The clinical relevance of longitudinal changes in subjective cognitive decline remains unclear.</p><p><strong>Objectives: </strong>To determine whether trajectories of self- or study partner-reported cognitive decline predict progression to mild cognitive impairment and reflect Alzheimer's disease-specific biological patterns.</p><p><strong>Design, setting, participants: </strong>Data were pooled from two observational cohorts. Cognitively unimpaired participants with baseline amyloid status, repeated assessments of subjective cognitive decline, and clinical follow-up were included. The study included 770 participants with a median follow-up of 5.0 years (interquartile range 4.0-7.0).</p><p><strong>Measurements: </strong>Subjective cognitive decline was assessed using the Everyday Cognition questionnaire completed by participants and study partners. Linear mixed-effects models examined associations with amyloid status and progression to mild cognitive impairment. Cox proportional hazards models tested whether one-year changes predicted progression.</p><p><strong>Results: </strong>Amyloid-positive participants and those who progressed to mild cognitive impairment showed steeper increases in self- and study partner-reported cognitive difficulties over time. Among amyloid-positive participants, only increases in study partner-report differentiated progressors from non-progressors. One-year increases in study partner-report predicted a higher risk of mild cognitive impairment compared with unchanged scores (hazard ratio 3.24; 95% confidence interval 1.73-6.07]), with effects confined to amyloid-positive participants.</p><p><strong>Conclusions: </strong>Short-term increases in study partner-reported cognitive difficulties identify amyloid-positive cognitively unimpaired older adults at increased risk of near-term progression to mild cognitive impairment. Longitudinal monitoring using study partner reports may provide a low-burden and clinically relevant approach for early risk stratification and surveillance in aging populations.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 8","pages":"100609"},"PeriodicalIF":7.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}