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

{"title":"Trajectories of muscle strength and physical performance preceding dementia in older US and European populations.","authors":"Youjin Jiang, Yi Ding, Qiuyu Cao, Xianglin Wu, Xiaoran Li, Yu Xu, Zhiyun Zhao, Min Xu, Jieli Lu, Tiange Wang, Guang Ning, Weiqing Wang, Yufang Bi, Yuchen Xu, Mian Li","doi":"10.1016/j.tjpad.2025.100296","DOIUrl":"10.1016/j.tjpad.2025.100296","url":null,"abstract":"<p><strong>Background: </strong>The association between muscle function and dementia risk remains elusive, as studies suggest that impaired muscle function may act as both a risk factor for and a consequence of dementia, hindering causal inference.</p><p><strong>Objectives: </strong>We aimed to clarify the temporal relationship between muscle function and incident dementia by investigating non-linear trajectories of muscle function in the years preceding dementia onset in older US and European populations.</p><p><strong>Design: </strong>Case-control study.</p><p><strong>Setting: </strong>Data were combined from the English Longitudinal Study of Ageing (ELSA, 2004-2018, waves 2-9), Health and Retirement Study (HRS, 2004-2018, waves 7-14), and Survey of Health, Ageing and Retirement in Europe (SHARE, 2004-2017, waves 1-7).</p><p><strong>Participants: </strong>For handgrip strength analysis, 18,335 participants aged 60 and older were included from the ELSA, HRS, and SHARE cohorts. For gait speed analysis, 11,690 participants aged 60 and older were included from the ELSA and HRS cohorts.</p><p><strong>Measurements: </strong>Muscle strength was assessed by handgrip strength using a Smedley dynamometer, and physical performance was evaluated by gait speed using the Timed 8-Foot Walk test, with assessments conducted biennially or quadrennially. Dementia was diagnosed using self-reported physician diagnosis and cognitive-functional assessments. Trajectories of muscle strength and physical performance were analyzed on a backward timescale using latent-process mixed models within a nested case-control design.</p><p><strong>Results: </strong>Significant differences in muscle function trajectories were observed between cases and controls 12 and 13 years prior to dementia onset (handgrip strength: coefficient [SE], -0.23 [0.05], P < 0.001; gait speed: coefficient [SE], -0.24 [0.08], P = 0.003). The pathological trajectories of handgrip strength and gait speed revealed periods of acceleration beginning 6 and 8 years prior to diagnosis, respectively. After adjusting for pre-dementia acceleration, greater handgrip (per 1-kg increment) was associated with a modest reduction in dementia risk (hazard ratio, 0.98; 95 % CI, 0.97-0.99), while faster gait speed (per 1-m/s increment) markedly lowered risk (hazard ratio, 0.35; 95 % CI, 0.23-0.53).</p><p><strong>Conclusions: </strong>These findings highlight muscle function as a cost-effective tool for early detection and dynamic monitoring of dementia risk and identify it as a modifiable target for prevention. Muscle function may also assist in identifying high-risk groups for preferential enrollment into clinical trials for dementia prevention and treatment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100296"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660297","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":"Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline.","authors":"Chao Tang, Yaqi Ding, Jiaxin Yang, Dian He","doi":"10.1016/j.tjpad.2025.100209","DOIUrl":"10.1016/j.tjpad.2025.100209","url":null,"abstract":"<p><strong>Background: </strong>The co-occurrence of Alzheimer's disease and cerebrovascular disease is increasingly prevalent in aging populations, yet the mechanisms of their interaction remain incompletely understood. This study aims to investigate the associations between CVD and AD and their composite effects on cognitive function, identifying key mediating pathways in these relationships.</p><p><strong>Methods: </strong>Participants underwent standardized clinical evaluations, detailed neuropsychological testing, and comprehensive neuropathological examinations. Structural equation modeling with multiple mediation analyses was employed to disentangle direct and indirect effects of vascular pathology on cognition and identify key mediating pathways. Relationships between specific cognitive domain assessments and whole brain and hippocampal volumes were analyzed, while interactions between traditional AD biomarkers (amyloid, tau) and vascular factors were examined.</p><p><strong>Results: </strong>CVD substantially increased AD risk. Structural equation modeling revealed that vascular factors influence cognitive performance primarily through hippocampal atrophy, APOE genotype, and cerebral atrophy. Participants with concomitant AD +CVD pathology displayed a distinctive hybrid pattern of brain-cognition relationships, with stronger correlations between hippocampal atrophy and cognitive performance compared to pure AD or CVD cases. Pathway-specific analysis demonstrated that hippocampal atrophy served as the strongest mediator of vascular effects on cognition, followed by cerebral atrophy and APOE genotype.</p><p><strong>Conclusion: </strong>Our findings demonstrate that cerebrovascular disease significantly increases the risk of Alzheimer's disease and substantially influences its clinical expression through multiple pathways, with structural brain changes serving as critical mediators of vascular effects on cognition. These results highlight the importance of addressing vascular health as an integral component of strategies to prevent and treat Alzheimer's disease and related cognitive disorders.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100209"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187972","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":"Synergistic effects of multiple pathological processes on Alzheimer's disease risk: Evidence for age-dependent stroke interactions.","authors":"Fen Liu, Xuesong Xia, Chengjie Zheng, Feng Liu, Min Jiang","doi":"10.1016/j.tjpad.2025.100268","DOIUrl":"10.1016/j.tjpad.2025.100268","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) pathogenesis involves complex interactions between multiple neuropathological processes, yet traditional approaches focus on individual markers. The cumulative effects of multiple pathologies and their interactions with cerebrovascular compromise and age remain poorly understood. This study aimed to develop a comprehensive Pathological Burden Score (PBS) and examine its relationship with AD risk, including interactions with stroke history and age.</p><p><strong>Methods: </strong>We analyzed 11,308 participants from the National Alzheimer's Coordinating Center database. A PBS was constructed integrating six neuropathological domains: Braak neurofibrillary tangle staging, CERAD neuritic plaque density, Thal amyloid-β phasing, stroke history, white matter rarefaction severity, and cerebral atrophy severity (range 0-16 points). PBS was categorized into four burden levels: low (0-4), moderate (5-8), high (9-12), and very high (13-16). Multivariable logistic regression examined associations between PBS categories and AD risk, with formal interaction testing for stroke × PBS effects. Age-stratified analyses were conducted using a 75-year cutpoint.</p><p><strong>Results: </strong>A clear dose-response relationship was observed between PBS and AD risk, with very high burden conferring over 5-fold increased odds compared to low burden. Significant stroke × PBS interaction was detected (interaction OR 1.23, p < 0.001), with stroke amplifying pathological burden effects. Among participants with very high burden, AD risk was 92.5 % in stroke patients versus 24.1 % in non-stroke patients. Age-dependent effects were profound: younger participants (<75 years) with high burden plus stroke showed 18.67-fold increased odds, while older participants (≥75 years) with equivalent burden showed 7.89-fold increased odds.</p><p><strong>Conclusions: </strong>Cumulative pathological burden demonstrates a strong dose-response relationship with AD risk, significantly amplified by stroke history. The pronounced age-dependent effects highlight the need for age-specific prevention strategies, with particular emphasis on aggressive vascular risk management in younger populations. These findings support comprehensive pathological burden assessment for enhanced risk stratification and personalized dementia care approaches.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100268"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650582","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":"Multimodal neuroimaging unveils basal forebrain-limbic system circuit dysregulation in cognitive impairment with depression: a pathway to early diagnosis and intervention.","authors":"Xiaowen Xu, Xiereniguli Anayiti, Peiying Chen, Zhongfeng Xie, Mengling Tao, Yongsheng Xiang, Mingyu Tan, Yingying Liu, Ling Yue, Shifu Xiao, Peijun Wang","doi":"10.1016/j.tjpad.2025.100298","DOIUrl":"10.1016/j.tjpad.2025.100298","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) frequently co-occurs with depressive symptoms, exacerbating both cognitive decline and clinical complexity, yet the neural substrates linking this co-occurrence remain poorly understood. We aimed to investigate the role of basal forebrain-limbic system circuit dysregulation in the interaction between cognitive impairment and depressive symptoms, identifying potential biomarkers for early diagnosis and intervention.</p><p><strong>Methods: </strong>This cross-sectional study included participants stratified into normal controls (NC), cognitive impairment without depression (CI-nD), and cognitive impairment with depression (CI-D). Multimodal MRI (structural, diffusion, functional, perfusion, iron-sensitive imaging) and plasma biomarkers were analyzed. Machine learning models classified subgroups using neuroimaging features.</p><p><strong>Results: </strong>CI-D exhibited distinct basal forebrain-limbic circuit alterations versus CI-nD and NC: (1) Elevated free-water fraction (FW) in basal forebrain subregions (Ch123/Ch4, p < 0.04), indicating early neuroinflammation; (2) Increased iron deposition in the anterior cingulate cortex and entorhinal cortex (p < 0.05); (3) Hyperperfusion and functional hyperactivity in Ch123 and amygdala; (4) Plasma neurofilamentlightchain exhibited correlated with hippocampal inflammation in CI-nD (p = 0.03) but linked to basal forebrain dysfunction in CI-D (p < 0.05). Multimodal support vector machine achieved 85 % accuracy (AUC=0.96) in distinguishing CI-D from CI-nD, with Ch123 and Ch4 as key discriminators. Pathway analysis in the CI-D group further revealed that FW-related neuroinflammation in the basal forebrain (Ch123/Ch4) indirectly contributed to cognitive impairment via structural atrophy.</p><p><strong>Conclusion: </strong>We identified a neuroinflammatory-cholinergic pathway in the basal forebrain as an early mechanism driving depression-associated cognitive decline. Multimodal imaging revealed distinct spatiotemporal patterns of circuit dysregulation, suggesting neuroinflammation and iron deposition precede structural degeneration. These findings position the basal forebrain-limbic system circuit as a therapeutic target and provide actionable biomarkers for early intervention in AD with depressive symptoms.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100298"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660296","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":"Targeting tau for Alzheimers disease through OGA inhibition.","authors":"Michael S Rafii","doi":"10.1016/j.tjpad.2025.100309","DOIUrl":"10.1016/j.tjpad.2025.100309","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100309"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708773","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":"Refining the evidence linking dietary diversity, genetic susceptibility, and dementia.","authors":"Hongye Yao, Yangbo Lv","doi":"10.1016/j.tjpad.2025.100247","DOIUrl":"10.1016/j.tjpad.2025.100247","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100247"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340391","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":"Structural equation modeling confirms interaction of Alzheimer's disease and vascular disease in hippocampal injury.","authors":"Gary A Rosenberg","doi":"10.1016/j.tjpad.2025.100255","DOIUrl":"10.1016/j.tjpad.2025.100255","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100255"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529619","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 Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity.","authors":"Julie M Chandler, Claire J Lansdall, Wenyu Ye, Fiona McDougall, Mark Belger, Balazs Toth, Xiaojuan Mi, Kaycee M Sink, Alexandra S Atkins","doi":"10.1016/j.tjpad.2025.100261","DOIUrl":"10.1016/j.tjpad.2025.100261","url":null,"abstract":"<p><strong>Background: </strong>Increasing dependence on informal and formal caregivers in Alzheimer's disease (AD) contributes to high societal cost. Treatments that delay time to increased dependence/care needs would be clinically meaningful, but these outcomes are rarely collected in early AD clinical trials. The 2015 ADCS-ADL dependence algorithm was created to estimate level of dependence in AD.</p><p><strong>Objectives: </strong>To revise the original dependence algorithm to improve accuracy of dependence scores (DS) across AD severity, including early symptomatic AD.</p><p><strong>Design: </strong>Secondary data analysis SETTING: Community cohort; randomized clinical trial PARTICIPANTS: 14,000 participants enrolled across GERAS-EU observational study and 12 AD clinical trials.</p><p><strong>Measurements: </strong>Three-phase algorithm revision: 1) reassess ADCS-ADL items to identify those appropriate for assessing dependence; 2) (a) assign individual item responses to degrees of assistance and (b) to operationalize assignment of DS based on extent of total assistance needed; and 3) validate revised algorithm in multiple datasets across AD severity from mild cognitive impairment due to AD to moderate-severe AD.</p><p><strong>Results: </strong>The revised DS (0-6) algorithm classified most participants with early symptomatic AD as independent or moderately independent (DS<3) at baseline. With disease progression over time, the proportion of participants who were mildly to fully dependent (DS≥3) increased across AD severity. Increased DS was associated with incremental worsening of clinical outcomes.</p><p><strong>Conclusions: </strong>The revised ADCS-ADL DS algorithm provides a supplementary approach to evaluate the impact of emerging treatments on independence/care needs in AD and may be useful in clinical trials where the ADCS-ADL has been collected.</p><p><strong>Clinical trial registration information: </strong>EXPEDITION 1 NCT00905372; EXPEDITION 2 NCT00904683; EXPEDITION 3 NCT01900665; AMARANTH NCT02245737; TRAILBLAZER-ALZ NCT03367403; TRAILBLAZER-ALZ 2 NCT04437511; GRADUATE I NCT03444870; GRADUATE II NCT03443973; CREAD NCT02670083; CREAD 2, NCT03114657; TAURIEL NCT03289143; LAURIET NCT03828747.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100261"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554948","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":"Blood-brain barrier water exchange and paramagnetic susceptibility alterations during anti-amyloid therapy: preliminary MRI findings.","authors":"Yuto Uchida, Yuya Kano, Hirohito Kan, Keita Sakurai, Hideyasu Morita, Yoshihiro Akagawa, Noriyuki Matsukawa, Kenichi Oishi","doi":"10.1016/j.tjpad.2025.100256","DOIUrl":"10.1016/j.tjpad.2025.100256","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100256"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544962","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":"A modelling approach to derive population-specific cutoff for plasma p-Tau217.","authors":"Tau Ming Liew","doi":"10.1016/j.tjpad.2025.100264","DOIUrl":"10.1016/j.tjpad.2025.100264","url":null,"abstract":"<p><p>Plasma pTau-217 shows promise for detecting Alzheimer's disease, but needs population-specific cutoffs for effective use. Conventional cutoff determination relies on invasive or costly gold-standards, limiting scalability. This study evaluated Finite Mixture Modelling (FMM) for establishing cutoffs without gold-standards. FMM was applied to derive cutoffs for Lumipulse plasma p-Tau217 and p-Tau217/Aβ42 ratio among 1039 ADNI participants, with validation conducted in a subset with amyloid PET data (n = 711). Additionally, simulations were conducted to determine the minimum sample size for reliable FMM estimation. The results showed that FMM-derived cutoffs effectively classified participants into brain amyloid-negative, -positive, and -indeterminate groups, with an indeterminate proportion <20 %, negative and positive predictive values near or above 90 %, and with p-Tau217/Aβ42 outperforming p-Tau217. These FMM-derived cutoffs demonstrated test performance that surpassed several previously-established cutoffs, including the recent FDA-approved cutoff. At least 900 samples were needed for reliable cutoff estimation. In conclusion, this study demonstrated the effectiveness of a modelling approach for estimating plasma p-Tau217 cutoffs without reliance on gold-standards. This approach simplifies the determinating of population-specific cutoffs and facilitates adoption of plasma p-Tau217 in communities lacking access to gold-standards, including some LMICs.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100264"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561232","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}