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

{"title":"Beyond amyloid positivity: Biological heterogeneity in the real-world use of lecanemab.","authors":"Michael S Rafii","doi":"10.1016/j.tjpad.2026.100584","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100584","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 6","pages":"100584"},"PeriodicalIF":7.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-based therapeutics for Alzheimer's disease and related tauopathies: challenges and opportunities.","authors":"Binita Rajbanshi, Ilaria Brentari, Michela Alessandra Denti, Jeffrey L Cummings, Anuj Guruacharya","doi":"10.1016/j.tjpad.2026.100585","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100585","url":null,"abstract":"<p><p>Tauopathies are neurodegenerative diseases characterized by pathological tau protein accumulation. Though therapies involving monoclonal antibodies and small-molecule inhibitors have progressed, they have so far failed in multiple clinical trials, underscoring the need for innovative molecular approaches. RNA-based therapies offer an alternative disease-modifying approach by being able to target tau at its molecular origin. Diverse modalities, such as mRNA, ASO, RNAi, and SSO, offer distinct promises. Though their challenges are equally diverse, they also share common problems. This review examines the nascent field of RNA therapeutics for tauopathies, outlining emerging modalities, translational barriers, molecular targets, clinical trials, and patent trends.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100585"},"PeriodicalIF":7.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Top five Alzheimer Disease trial eligibility criteria favor men compared to women in a clinic-based cohort.","authors":"Lieza G Exalto, Siti S Syaziyah, Xiaotian T Fang, Niels D Prins, Sietske A M Sikkes, Wiesje M van der Flier, Everard G B Vijverberg, Yvonne M F Lim","doi":"10.1016/j.tjpad.2026.100580","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100580","url":null,"abstract":"<p><strong>Background: </strong>Less women participate in Alzheimer Disease (AD) trials compared to their estimated representation in the global dementia population.</p><p><strong>Objectives: </strong>We aimed to apply five most commonly used eligibility criteria to a real-world memory clinic population to compare male and female eligibility according to these criteria.</p><p><strong>Design: </strong>Observational.</p><p><strong>Setting: </strong>Memory clinic setting.</p><p><strong>Participants: </strong>Consecutive patients (2000-2024) from Amsterdam Dementia Cohort with a diagnosis of mild cognitive impairment (MCI) or AD (n = 3835).</p><p><strong>Measurements: </strong>Free-text eligibility criteria of n = 608 phase II and III AD drug trials were downloaded from ClinicalTrials.gov (March 28, 2025). A machine-learning model was trained and validated to extract all eligibility criteria. Next the criteria were applied on observational real world data from on memory clinic diagnostic work-up.</p><p><strong>Results: </strong>Top 5 most common AD clinical trial eligibility criteria were 1) no other central nervous system disorder related to cognitive impairment (84%), 2) participation of a caregiver (72%), 3) MMSE (66%, range 20-30), 4) no comorbidities, specifically vascular and mental health (62%), 5) no contra-indications for study procedures such as lumbar puncture, MRI and PET (59%). Applying the abovementioned criteria results in 33% of men and 23% of women remaining eligible (p<.001). Main reason for non-eligibility is caretaker absence (applicable for 20% of men and 38% of women) and low MMSE (32% of man and 54% of women).</p><p><strong>Conclusion: </strong>Based on five commonly used eligibility criteria of AD clinical trials, women in our clinic-based cohort are less eligible for participation in AD drug trials than men. This discrepancy was mainly attributed to lack of caregiver presence and lower MMSE at presentation. These results provide clues for trial design to facilitate more equal inclusion of women.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100580"},"PeriodicalIF":7.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep complaints and genetic risk of Alzheimer's disease in older women: associations with memory and tau deposition.","authors":"Kitty K Lui, Xin Wang, Melanie A Dratva, Ella T Lifset, Jordan Stiver, Nadine C Heyworth, Qian Shen, Michael Thomas, Pamela N DeYoung, Atul Malhotra, Erin E Sundermann, Sarah J Banks","doi":"10.1016/j.tjpad.2026.100581","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100581","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence point to a bidirectional relationship between sleep disturbances and Alzheimer's disease (AD). Poor sleep may be an overlooked risk factor for older women, who are disproportionately affected by AD and report worse subjective sleep quality than men. High genetic AD risk-characterized by the polygenic hazard score (PHS), including apolipoprotein (APOE) ε4 carriership-may further compound the effects of disrupted sleep on AD, particularly for older women.</p><p><strong>Objective: </strong>This study examined the moderating effect of genetic AD risk on subjective sleep as it related to memory and tau burden in a sample of older women.</p><p><strong>Participants: </strong>The sample consisted of older women (≥65 years old) from the Women Inflammation Tau Study.</p><p><strong>Measurement: </strong>Participants completed the Pittsburgh Sleep Quality Index (PSQI), Rey Auditory Learning Test, and Brief Visuospatial Memory Test-Revised. They also underwent [18]F-MK6240 positron emission tomography. Tau burden was calculated in composite regions across Braak stages. Genetic risk groups were characterized by PHS stratified at the 75th percentile. PSQI global score × PHS group interactions on memory composite scores (N = 69) and tau burden (N = 63) were examined.</p><p><strong>Results: </strong>PSQI global score × PHS group interactions were observed on visual memory and pathological tau in Braak regions III/IV (ps<0.10). Poorer subjective sleep was associated with worse visual memory and greater limbic tau deposition only among higher genetic risk women (ps<0.04). No significant associations were observed for verbal memory or tau in Braak regions I/II or V/VI.</p><p><strong>Conclusion: </strong>Older women with elevated genetic AD risk and subjective sleep difficulties may be at greater risk for visual memory deficits and tau burden in regions affected in early AD. This suggests that sleep complaints may represent a promising AD risk factor. Improving sleep may be a potential intervention target for AD mitigation and prevention, particularly for older women.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100581"},"PeriodicalIF":7.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarity AD open-label extension data do not robustly confirm disease course modification by lecanemab in ApoE₄ heterozygotes and non-carriers.","authors":"Jemma Hazan, Kathy Y Liu, Robert Howard","doi":"10.1016/j.tjpad.2026.100587","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100587","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100587"},"PeriodicalIF":7.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual reality-based training in patients with alzheimer's disease: A systematic review and meta-analysis.","authors":"Junjie Wang, Can Wu, Kedong Zhu, Xiaoshan Qi, Guiqin Chen","doi":"10.1016/j.tjpad.2026.100590","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100590","url":null,"abstract":"<p><strong>Background and objectives: </strong>Prior meta-analyses have suggested that training utilizing virtual reality (VR) serves as a secure and effective intervention for elderly individuals experiencing mild cognitive impairment (MCI). Nevertheless, the effectiveness of such interventions appears to differ among various populations and cognitive domains. Furthermore, there remains a significant gap in understanding the effectiveness of VR-based training, specifically among individuals diagnosed with Alzheimer's disease (AD).</p><p><strong>Methods: </strong>The researchers conducted a comprehensive search of databases, including Web of Science, PubMed, Cochrane Library, and EMBASE up until July 1, 2025, focusing on randomized controlled trials that investigated VR-based training in patients diagnosed with AD. The outcomes measured were categorized and analyzed separately, encompassing overall cognitive performance, distinct cognitive domains, psychosocial function, physical capabilities, and the execution of daily living activities within the context of AD trials.</p><p><strong>Results: </strong>Of the 265 publications identified, 11 (4.15%) randomized controlled trials (RCTs) eventually met all eligibility criteria. Those who received VR-based training showed significantly better global cognitive function [SMD (95%CI) = 0.44 (0.21-0.68)] and Short-term memory [SMD (95%CI) = 0.62 (0.25-0.99)] than the controls. However, no significant improvements were observed in areas such as executive function, spatial memory, activities of daily living, quality of life, balance and coordination, fear of falling, risk of falls, and depression levels.</p><p><strong>Conclusion: </strong>VR-based interventions demonstrated beneficial effects on global cognitive function and short-term memory in AD populations. Due to the small sample size, the current research on evidence for efficacy in people with AD is weak and limited in many indicators.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100590"},"PeriodicalIF":7.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetanus, diphtheria and pertussis vaccination and risk for incident dementia among adults with down syndrome.","authors":"Kimberly Schiel, Joanne Salas, Anjani Urban, Daniel F Hoft, Jeffrey F Scherrer","doi":"10.1016/j.tjpad.2026.100583","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100583","url":null,"abstract":"<p><strong>Background: </strong>Adult vaccination is inversely associated with incident Alzheimer's Disease and Related Dementias.</p><p><strong>Objectives: </strong>We determined if Tetanus, Diphtheria and Pertussis (Tdap) vaccination was linked to incident Alzheimer's Disease and dementia among adults with Down Syndrome, 50% of whom develop Alzheimer's Disease by age 60.</p><p><strong>Design: </strong>This is a retrospective cohort study using TriNetX nationally distributed electronic health records from 2013 to 2024.</p><p><strong>Setting: </strong>Historical medical record data.</p><p><strong>Participants: </strong>5591 patients with Down Syndrome across the United States. Eligible patients were free of Alzheimer's Disease and dementia prior to index. Index date could occur 1/1/2015 to 1/1/2020 allowing for 5 to 10 years of possible follow-up time.</p><p><strong>Measurements: </strong>Vaccination was measured using product name and procedure codes and Alzheimer's Disease and dementias was defined by ICD-10 codes.</p><p><strong>Results: </strong>The mean age of the cohort was 50.0 (±8.3), 50.1% were female and 72.1% were White. After controlling for confounding, Tdap vaccination vs. remaining without Tdap vaccination was associated with lower Alzheimer's Disease and dementia risk (HR=0.74; 95%CI:0.57-0.98).</p><p><strong>Conclusions: </strong>In a cohort of patients with Down Syndrome, Tdap vaccination was associated with a 26% lower risk for Alzheimer's Disease and dementia. This is a novel and important finding because existing studies of vaccination and reduced risk for Alzheimer's Disease and dementia have been among cognitively intact adults. This study reveals benefits of vaccination even among those at high risk for Alzheimer's Disease and dementia due to Down Syndrome. Future studies are needed to understand the mechanisms underlying this relationship.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100583"},"PeriodicalIF":7.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of plasma biomarkers with age in the presenilin-1 E280A autosomal dominant Alzheimer's disease kindred.","authors":"Vincent Malotaux, Vivian Ku, Paula Ospina Lopera, Yi Su, Yinghua Chen, Alpana Singh, Jonathan Ruiz-Triviño, María José Hidalgo, Laura Osorio, Laura Serna, Daniela Giraldo, Diana Alzate, Bing He, Catarina Tristão-Pereira, Liliana Ramirez Gomez, Sonia Do Carmo, A Claudio Cuello, Nicholas J Ashton, Eric M Reiman, David Aguillón, Yakeel T Quiroz","doi":"10.1016/j.tjpad.2026.100578","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100578","url":null,"abstract":"<p><strong>Background: </strong>Autosomal-dominant Alzheimer's disease (ADAD) offers a model to define early biological changes in Alzheimer's disease due to its predictable age at symptom onset. Although ultrasensitive plasma assays are available, their associations with age in ADAD remain incompletely characterized.</p><p><strong>Objectives: </strong>To characterize age-related changes in plasma biomarkers and examine associations with cognition in PSEN1 E280A ADAD.</p><p><strong>Design and setting: </strong>Cross-sectional observational study in members of the Colombian PSEN1 E280A kindred.</p><p><strong>Participants: </strong>A total of 164 individuals were included, comprising 83 mutation carriers (mean age 34.36±9.82 years; 54% female) and 81 non-carriers (mean age 33.75±9.84 years; 52% female).</p><p><strong>Measurements: </strong>Plasma Aβ42/Aβ40, phospho-tau217 (p-tau217), brain-derived tau (BD-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were quantified. Sex-adjusted associations with age, divergence ages between groups, classification performance (ROC curves), and associations with cognition (MMSE and CERAD delayed recall) were assessed.</p><p><strong>Results: </strong>All plasma biomarkers were associated with age (p < .01). Divergence between carriers and non-carriers began with Aβ42/Aβ40 before age 18, followed by p-tau217 (26.0 years), GFAP (26.1 years), BD-tau (27.9 years), and NfL (38.7 years). Aβ42/Aβ40 showed the highest discrimination of mutation status (AUC=0.99), followed by p-tau217 (AUC=0.87) and GFAP (AUC=0.84). Among carriers, p-tau217, GFAP, BD-tau, and NfL were associated with MMSE, while p-tau217, GFAP, and NfL predicted CERAD delayed recall.</p><p><strong>Conclusion: </strong>Plasma biomarkers exhibit a temporal cascade in PSEN1 E280A ADAD. P-tau217 and GFAP show the strongest associations with early cognitive decline, suggesting their potential utility for tracking disease progression and monitoring treatment effects in E280A carriers.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 6","pages":"100578"},"PeriodicalIF":7.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hazan J; Liu KY; Howard R. Clarity AD open-label extension data do not robustly confirm disease course modification by lecanemab in ApoE4 heterozygotes and non-carriers. # TJPAD-D-26-00165.","authors":"Lutz Froelich","doi":"10.1016/j.tjpad.2026.100588","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100588","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100588"},"PeriodicalIF":7.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting the spanish healthcare system for disease-modifying treatments in early-stage alzheimer's disease.","authors":"R Sánchez Valle, A Lleó Bisa, A Villarejo Galende, E Cuartero Rodríguez, J Escudero-Torrella, N Bargallo Alabart","doi":"10.1016/j.tjpad.2026.100586","DOIUrl":"https://doi.org/10.1016/j.tjpad.2026.100586","url":null,"abstract":"<p><strong>Background: </strong>The emergence of disease-modifying therapies targeting amyloid pathology represents a major paradigm shift in the management of Alzheimer disease (AD). However, their implementation poses substantial organizational, infrastructural, and clinical challenges for health systems.</p><p><strong>Objectives: </strong>To identify the key challenges and establish priority recommendations for the effective incorporation of amyloid-targeting therapies into the Spanish National Health System.</p><p><strong>Design, setting, and participants: </strong>This multiphase consensus study was conducted within the Spanish National Health System between September 2024 and July 2025. The study comprised a narrative literature review, qualitative research, regional workshops, and a modified RAND/UCLA Delphi process. A total of 56 experts participated, including a scientific committee of 6 Alzheimer disease specialists and an expert panel of 50 multidisciplinary professionals involved in AD care.</p><p><strong>Measurements: </strong>Identification of key challenges across the AD care pathway; development, evaluation, and prioritization of consensus-based recommendations; and estimation of patient demand, including projected increases in day hospital activity and magnetic resonance imaging utilization.</p><p><strong>Results: </strong>Ten key challenge areas were identified, encompassing early detection and referral, diagnostic confirmation, assessment of patient eligibility, treatment administration in day hospitals, monitoring of amyloid-related imaging abnormalities, evaluation of treatment effectiveness, infrastructure and capacity, professional training, patient information and support, and health care planning. Of the 43 recommendations assessed, 38 were rated as appropriate and necessary, with 14 prioritized for immediate implementation. Demand estimation models indicated that 11 to 26 patients per 100,000 inhabitants could be treated under current care patterns, increasing to 17 to 115 per 100,000 inhabitants under alternative eligibility scenarios.</p><p><strong>Conclusions: </strong>This consensus defines the clinical, organizational, and infrastructural requirements necessary to integrate amyloid-targeting therapies into routine care within the Spanish National Health System. The prioritized recommendations define immediate actions to address the challenges identified and may serve as a reference for other health systems facing similar implementation processes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"13 7","pages":"100586"},"PeriodicalIF":7.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}