Alzheimer's & Dementia最新文献

{"title":"World Dementia Council Update","authors":"","doi":"10.1002/alz.70691","DOIUrl":"10.1002/alz.70691","url":null,"abstract":"<p>As scientific understanding, treatment advances, and interventions related to brain health continue to progress, advocacy strategies must also adapt. There is an increasing need to engage scientists, the public, governmental organizations, and other stakeholders to shape advocacy priorities and refine messaging. On July 30, 2025, the World Dementia Council (WDC), in partnership with the Alzheimer's Association, held a breakfast at the Alzheimer's Association International Conference (AAIC) in Toronto. This gathering brought together key players in policy, research, and program development to discuss emerging opportunities in Alzheimer's and dementia advocacy.</p><p>Dr. Joanne Pike, President and CEO of the Alzheimer's Association and chair of the WDC opened the meeting by highlighting the important shift in the dementia landscape, moving from a focus on research and care to one that also includes medical delivery. With this transition, advocacy becomes more important than ever to ensure that equity and access are central to treatment and service delivery. Lenny Shallcross, Executive Director of the WDC, expanded on these points, reiterating the urgency and opportunity of the current moment. Scientific advancements, particularly in prevention and diagnostics, have created new momentum. However, to make a lasting impact, efforts must be sustainable, inclusive, and scalable. As dementia becomes integrated into public health systems, advocacy efforts must adapt, bringing in new voices and perspectives to ensure continued progress.</p><p>To provide scientific context, Dr. Rebecca Edelmeyer, Vice President, Scientific Engagement, at the Alzheimer's Association and Dr. Donna Wilcock, Professor of Alzheimer's Disease Research and Neurology at Indiana University, shared updates and learnings from AAIC related to biomarkers, pathogenesis of disease, risk reduction, and treatment. A major highlight of the conference was the announcement of the positive results from the US POINTER study, which demonstrated the effectiveness of lifestyle-based risk reduction strategies. These findings represent a promising path forward, but will require a coordinated public health strategy to implement effectively across different communities. Other important updates included progress in the diagnostic pipeline, precision medicine, and the development of tools and guidelines, including new global guidelines on blood-based biomarkers.</p><p>Following the scientific updates, panelists convened to discuss how to translate these advances into global advocacy action.</p><p>Rob Egge, Chief Public Policy Officer at the Alzheimer's Association, emphasized that advocacy is not just important, but essential to achieving meaningful change within an acceptable timeframe. However, it requires sustained effort, organizational commitment, and meaningful public engagement. He encouraged advocates and organizations to pursue underexplored strategies and spaces, as this is where the change ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NACC data: Who is represented over time and across centers, and implications for generalizability","authors":"Kwun C. G. Chan,&nbsp;Fan Xia,&nbsp;Walter A. Kukull","doi":"10.1002/alz.70657","DOIUrl":"10.1002/alz.70657","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Since 2005, the Alzheimer's Disease Research Centers (ADRCs) have recruited participants into the Uniform Data Set (UDS), but enrollment trends and center-level differences remain underexplored. This study investigates temporal patterns and heterogeneity in recruitment across ADRCs, with implications for generalizability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from the National Alzheimer's Coordinating Center (NACC), we assessed trends and between-center variation in baseline characteristics, including age, sex, race, education, clinical diagnosis, referral source, family history, and co-participant relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>All characteristics except sex and family history showed directional shifts over time. Substantial between-center heterogeneity was observed in all variables examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Temporal changes and site-level variability in participant profiles highlight challenges and opportunities for generalizing findings from UDS data. Although not nationally representative, statements about generalization could often be made using UDS data, with strengthened inferences and enhanced transparency through analytic approaches such as sensitivity analysis or meta-analytic techniques treating centers as separate studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The National Alzheimer's Coordinating Center (NACC) Uniform Data Set has enrolled participants for 20 years across more than 40 centers.</li>\u0000 \u0000 <li>We identified temporal trends and site-level variation in participant characteristics in the initial visit.</li>\u0000 \u0000 <li>Despite being a volunteer sample, modern epidemiologic and biostatistical approaches can help assess and enhance the generalizability of scientific findings derived from NACC data.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between cardiovascular and cognitive health among older Indigenous Africans: Data from an urban Nigerian settlement participating in the VALIANT study","authors":"Rufus O. Akinyemi,&nbsp;Oladotun V. Olalusi,&nbsp;Gabriel O. Ogunde,&nbsp;Tolulope O. Akinyemi,&nbsp;Joseph O. Yaria,&nbsp;Olabode Oguntiloye,&nbsp;Ayotomiwa Fagbemi,&nbsp;Eniola O. Cadmus,&nbsp;Femi O. Popoola,&nbsp;Mayowa Ogunronbi,&nbsp;Dorcas Olujobi,&nbsp;Olaoluwa Famuyiwa,&nbsp;Joshua O. Akinyemi,&nbsp;Mayowa O. Owolabi,&nbsp;Roman Romero-Ortuno,&nbsp;Adesola Ogunniyi,&nbsp;Rajesh N. Kalaria,&nbsp;Brian Lawlor","doi":"10.1002/alz.70669","DOIUrl":"10.1002/alz.70669","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The relationship between cardiovascular health (CVH) and cognitive health (CH) has been established in diverse populations but is understudied among indigenous Africans. We investigated the association between CVH and CH in 1031 older Nigerian Africans participating in the Vascular heAlth, fraiLty, and cognItion in Ageing Nigerians sTudy (VALIANT).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CVH was assessed by the Life's Simple 7 (LS7) score. CH was measured using three validated metrics of general cognitive well-being: Montreal Cognitive Assessment (MoCA), Community Screening Instrument for Dementia (CSID), and Identification and Intervention for Dementia in Elderly Africans (IDEA). Frailty was evaluated using Rockwood's Clinical Frailty Scale. Multivariable linear regression was performed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Individual LS7 metrics, including poor diet, ideal body mass index (overall), and intermediate blood pressure (among female participants), showed independent relationships with poor CH. Although the LS7 composite score showed a significant univariate relationship with MoCA and IDEA scores, the independent determinants of general CH were older age, low educational attainment, and clinical frailty, but not LS7 composite score&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In a sample of older Nigerian Africans, the LS7 composite score may not accurately characterize the relationship between CVH and CH. Afrocentric CVH composite scores incorporating measures that are more sensitive to outcomes in Africans are needed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;We determined the association between cardiovascular health (CVH) and cognitive health (CH) in 1031 urban-dwelling Nigerian Africans.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Although individual Life's Simple 7 (LS7) metrics such as poor diet, intermediate blood pressure, and ideal body mass index showed independent association with poor CH, the composite LS7 metric showed no association.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;In a sample of Nigerian Africans, the LS7 score as a composite vascular marker may not accurately characterize the relationship between CVH and CH.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Afrocentric composite scores incorporating risk markers potentially unique to indigenous Africa","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids","authors":"Min Young Chun,&nbsp;Sang-Hyuk Jung,&nbsp;Juran Choe,&nbsp;Seung-yeon Lee,&nbsp;Hang-Rai Kim,&nbsp;Hyo Jin Son,&nbsp;Yejoo Choi,&nbsp;Minyoung Cho,&nbsp;Beomsu Kim,&nbsp;Hyemin Jang,&nbsp;Seong Hye Choi,&nbsp;Jee Hyang Jeong,&nbsp;Sang Joon Son,&nbsp;Chang Hyung Hong,&nbsp;Hyun Woong Roh,&nbsp;Duk L. Na,&nbsp;Sang Won Seo,&nbsp;Hong-Hee Won,&nbsp;Jinsoo Seo,&nbsp;Hee Jin Kim","doi":"10.1002/alz.70660","DOIUrl":"10.1002/alz.70660","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Polygenic risk score (PRS) identifies individuals at high genetic risk for Alzheimer's disease (AD), but its utility in predicting cognitive trajectories and AD pathologies remains unclear. We optimized PRS (optPRS) for AD, investigated its association with cognitive trajectories and AD phenotypes of cerebral organoids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using genome-wide association study (GWAS) summary statistics from a European population, we developed optPRS to predict AD in Korean individuals (n = 1634). We analyzed the association between optPRS and cognitive trajectories (n = 771). We generated induced pluripotent stem cell–derived cerebral organoids from patients with high (n = 3) and low (n = 4) optPRS to evaluate amyloid beta (Aβ) and phosphorylated tau (p-tau) levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>OptPRS predicted AD dementia and Aβ positivity, independent of apolipoprotein E (<i>APOE</i>). Higher optPRSs correlated with rapid cognitive decline. Cerebral organoids from the high optPRS group exhibited increased Aβ insolubility and p-tau levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug-screening platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Optimized polygenic risk scores (optPRSs) improve the prediction of Alzheimer's disease (AD) dementia and amyloid beta positivity (Aβ+).</li>\u0000 \u0000 <li>High optPRS is associated with faster cognitive decline, particularly in Aβ+.</li>\u0000 \u0000 <li>Induced pluripotent stem cell (iPSC)–derived cerebral organoids from high optPRSs show high Aβ insolubility and phosphorylated tau (p-tau).</li>\u0000 \u0000 <li>PRS genetic risk stratification provides insight into AD progression and pathology.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond NACC's Uniform Data Set for cognition: the impact of additional items on measurement precision","authors":"Seo-Eun Choi,&nbsp;Shubhabrata Mukherjee,&nbsp;Laura E. Gibbons,&nbsp;Emily H. Trittschuh,&nbsp;Michael Lee,&nbsp;Phoebe Scollard,&nbsp;R. Elizabeth Sanders,&nbsp;Beth E. Snitz,&nbsp;C. Elizabeth Shaaban,&nbsp;Oscar L. Lopez,&nbsp;Jesse Mez,&nbsp;Andrew J. Saykin,&nbsp;Timothy J. Hohman,&nbsp;Paul K. Crane","doi":"10.1002/alz.70694","DOIUrl":"10.1002/alz.70694","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We sought to determine the implications of integrating additional cognitive test items beyond the items of the Uniform Data Set (UDS) administered by Alzheimer's Disease Research Centers (ADRCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We considered the UDS 1&amp;2 and UDS 3 cognitive batteries alone (“UDS-only”) and compared them to batteries augmented with additional items (“UDS-augmented”) administered by the University of Pittsburgh, ADRC. We used confirmatory factor analyses to co-calibrate and harmonize three cognitive domains (memory, executive functioning, and language). Then we compared the UDS-only and UDS-augmented with respect to measurement precision, sample sizes required to detect 25% differences in rates of decline, and association between baseline scores and the hazard of converting from mild cognitive impairment to AD dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>UDS-augmented substantially enhanced measurement precision across all cognitive domains for UDS 1&amp;2 and UDS 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>There is substantial value in integrating item content beyond the UDS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We considered items from the UDS 1&amp;2 and UDS 3 cognitive batteries alongside augmented site-specific content for the memory, executive functioning, and language domains.</li>\u0000 \u0000 <li>Augmented scales improved measurement precision in each case.</li>\u0000 \u0000 <li>As expected, improved measurement precision facilitated better performance for each scale.</li>\u0000 \u0000 <li>It would be useful to integrate multiple sources of cognitive data into comprehensive estimates of domain performance.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopment and neural environment inform Alzheimer's disease age at onset and phenotype","authors":"Zachary A. Miller,&nbsp;Rik Ossenkoppele,&nbsp;Neill R. Graff-Radford,&nbsp;Isabel E. Allen,&nbsp;Wendy Shwe,&nbsp;Lynne Rosenberg,&nbsp;Dustin J. Olguin,&nbsp;Michael G. Erkkinen,&nbsp;P. Monroe Butler,&nbsp;Salvatore Spina,&nbsp;Jennifer S. Yokoyama,&nbsp;Rahul S. Desikan,&nbsp;Philip Scheltens,&nbsp;Wiesje van der Flier,&nbsp;Yolande Pijnenburg,&nbsp;Emma Wolters,&nbsp;Rosa Rademakers,&nbsp;Daniel H. Geschwind,&nbsp;Joel H. Kramer,&nbsp;Howard J. Rosen,&nbsp;Katherine P. Rankin,&nbsp;Lea T. Grinberg,&nbsp;William W. Seeley,&nbsp;Virginia Sturm,&nbsp;David C. Perry,&nbsp;Bruce L. Miller,&nbsp;Gil D. Rabinovici,&nbsp;Maria Luisa Gorno-Tempini","doi":"10.1002/alz.70668","DOIUrl":"10.1002/alz.70668","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Risk factors associated with sporadic non-amnestic and early-onset Alzheimer's disease (AD) remain underexamined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We investigated a large, clinically heterogeneous, AD cohort for frequencies of established risk factors (hypertension, hypercholesterolemia, diabetes mellitus) alongside novel factors (non–right-handedness, learning disability, seizures, autoimmune disease).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Early-onset AD possessed lower frequencies of established risk factors (hypertension, hypercholesterolemia, diabetes mellitus, all <i>p </i>&lt; 0.001) and higher frequencies of novel factors (non–right-handedness, learning disability, active seizure, all <i>p </i>&lt; 0.001; remote seizure, <i>p</i> = 0.002; and autoimmune disease, <i>p </i>= 0.007). An age at onset &lt; 70 maximally distinguished novel from typical factors. Principal component analysis loaded novel factors into two components, non–right-handedness and learning disability versus seizure and autoimmune disease, which combined, resulted in an exponential decrease in age at onset from one factor alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Identifying novel factors enriched in early-onset and non-amnestic AD introduces new theories of AD susceptibility and phenotypic heterogeneity, with significant implications for disease prediction and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We identified a suite of novel factors overrepresented in early-onset and non-amnestic AD.</li>\u0000 \u0000 <li>These factors can be broadly conceptualized as neurodevelopmental (non–right-handedness and learning disability) and neural environmental (seizure and autoimmunity).</li>\u0000 \u0000 <li>The combination of these factors produced exponential decreases in AD age at onset, compared to each alone, supporting a new theoretical framework for understanding AD risk with implications for disease prediction, prevention, and therapeutic intervention.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes","authors":"Jackie Shuk Man Tsui,&nbsp;Danise M. Au,&nbsp;Hyebin Uhm,&nbsp;Wan-wa Wong,&nbsp;Ronnie Ming Nok Lo,&nbsp;Yuanbing Jiang,&nbsp;Fanny C. F. Ip,&nbsp;Kin Y. Mok,&nbsp;Hiu Yi Wong,&nbsp;Timothy C. Y. Kwok,&nbsp;Amy K. Y. Fu,&nbsp;Nancy Y. Ip","doi":"10.1002/alz.70586","DOIUrl":"10.1002/alz.70586","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Multiple <i>TREM2</i> variants are associated with an increased risk of Alzheimer's disease (AD). <i>TREM2</i> H157Y is the only variant located at the proteolytic cleavage site that enhances TREM2 protein shedding. While this variant is associated with increased AD risk predominantly in the Chinese population, its impact on AD pathology is largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted an in-depth study integrating clinical cases, neuroimaging data, and blood proteomic data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>TREM2</i> H157Y variant carriers with AD exhibit more severe AD pathology, more severe neurodegeneration, and more rapid clinical progression. Cognitively normal individuals carrying the variant show changes in blood proteins that are associated with neurodegeneration and inflammation. Moreover, the <i>TREM2</i> H157Y variant is associated with altered immune and vascular processes irrespective of disease state.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings highlight the clinical implications of the <i>TREM2</i> H157Y variant and the use of blood proteomic data to investigate the effects of genetic variants on disease-related endophenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The <i>TREM2</i> H157Y variant is associated with more rapid clinical progression of Alzheimer's disease only in the presence of the apolipoprotein E (<i>APOE)</i> ε4 allele.</li>\u0000 \u0000 <li>The <i>TREM2</i> H157Y variant is associated with neurodegeneration, irrespective of disease state.</li>\u0000 \u0000 <li>The <i>TREM2</i> H157Y variant is associated with altered immune and vascular processes, irrespective of disease state.</li>\u0000 \u0000 <li>Cognitively normal <i>TREM2</i> H157Y carriers show altered disease-associated blood proteins related to peripheral immune response.</li>\u0000 \u0000 <li>Blood proteomic data can be used to study the impacts of disease-associated genetic variants on disease outcomes and biological processes involved in pathogenesis.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-year change in sleep duration and incident Alzheimer's Disease and Related Dementias among lower-income older adults","authors":"Hui Shi,&nbsp;Loren Lipworth,&nbsp;Qian Xiao,&nbsp;Xijing Han,&nbsp;Michael Mumma,&nbsp;Laura M. Keohane,&nbsp;Danxia Yu,&nbsp;Corey J. Bolton,&nbsp;Derek B. Archer,&nbsp;Timothy J. Hohman,&nbsp;Kelsie M. Full","doi":"10.1002/alz.70678","DOIUrl":"10.1002/alz.70678","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Little is known about change in sleep duration over time and Alzheimer's Disease and Related Dementias (ADRD) risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>ADRD cases were identified among Southern Community Cohort Study participants enrolled in Medicare. Sleep duration was reported at enrollment and first study follow-up and categorized (short (&lt; 7 hours), recommended (7-9) and long (&gt; 9)), change was calculated between timepoints. Adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified 2,093 ADRD cases among 17,945 participants. Compared to maintaining optimal sleep duration (7-9 hours) over 5 years, suboptimal changes were associated with 20-69% greater ADRD risk: adjusted HR (95% CI) was 1.50 (1.23-1.82) for long-recommended, 1.56 (1.21-2.01) for long-long, 1.69 (1.25-2.27) for long-short, 1.49 (1.16-1.91) for short-long, and 1.20 (1.06-1.36) for short-short.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Suboptimal 5-year change in sleep durations were associated with ADRD risk among lower-income adults underrepresented in ADRD research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The study calculated 5-year change in sleep duration in a large community-based cohort of predominately lower-income adults.</li>\u0000 \u0000 <li>Cases of Alzheimer's Disease and Related Dementias (ADRD) were ascertained from Medicare claims data among 17,945 participants with up to 12 years of follow-up.</li>\u0000 \u0000 <li>Compared to maintaining 7-9 hours of sleep, older adults with suboptimal sleep categories were consistently at a greater risk of ADRD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA cargo in neuron-derived vesicles as peripheral biomarkers of brain insulin dysregulation","authors":"Jacob Alexander Cleary,&nbsp;Ashish Kumar,&nbsp;Yixin Su,&nbsp;Sangeeta Singh,&nbsp;Fang-Chi Hsu,&nbsp;Suzanne Craft,&nbsp;William Harrison,&nbsp;C. Dirk Keene,&nbsp;Marjorie Howard,&nbsp;Kathleen M. Hayden,&nbsp;Mark A. Espeland,&nbsp;Jingzhong Ding,&nbsp;Gagan Deep","doi":"10.1002/alz.70597","DOIUrl":"10.1002/alz.70597","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Brain insulin resistance (bIR) is a risk factor for Alzheimer's disease (AD). However, the association between bIR and peripheral insulin resistance and their effects on cognition remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Here, we analyzed the expression of key genes (<i>n</i> = 84) involved in insulin signaling in brain tissue collected from healthy and AD subjects, as well as regulatory microRNAs (miRNAs) in the brain tissue and tissue-derived small extracellular vesicles (sEV). Subsequently, miRNA expression was analyzed in plasma neuron-derived sEV (NDE) of a second cohort consisting of cognitively normal and adjudicated mixed dementia (aMD) subjects, all with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Analysis of miRNAs in brain tissue and their sEV revealed significant and concordant dysregulation. NDE demonstrated similar changes in specific miRNA expression, with significant upregulation exclusively in male aMD subjects, and showed correlation with cognition and plasma β-amyloid (Aβ) 1-40 and Aβ1-42.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>NDE may serve as a liquid biopsy to determine sex-specific bIR and cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Insulin signaling is disrupted in brain tissue with Alzheimer's disease (AD).</li>\u0000 \u0000 <li>microRNAs (miRNAs) regulate insulin signaling and insulin resistance.</li>\u0000 \u0000 <li>miRNAs in neuron-derived small extracellular vesicles (sEV) could serve as biomarkers for brain insulin signaling.</li>\u0000 \u0000 <li>Brain insulin signaling biomarkers in neuron-derived sEV (NDE) could predict cognitive impairment.</li>\u0000 \u0000 <li>Sex-specific differences exist in brain insulin resistance biomarkers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCRAD: Advancing Alzheimer's research through high-quality biospecimens and data","authors":"Michael C. Edler,&nbsp;Kelley Faber,&nbsp;Kaci Lacy,&nbsp;Jacqueline Jackson,&nbsp;Tatiana Foroud","doi":"10.1002/alz.70682","DOIUrl":"10.1002/alz.70682","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;The National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) was established in 2002 to support research on the genetics of Alzheimer's disease. NCRAD quickly became a central resource, banking samples from numerous studies and distributing them to researchers worldwide. As genetic risk variants were identified, NCRAD prepared for functional studies by expanding its collections to include peripheral blood mononuclear cells (PBMCs), RNA, and biofluids. Over the past decade, NCRAD's extensive repository of plasma, serum, and cerebrospinal fluid was essential to the development of fluid biomarkers. NCRAD's rigorous best practices for sample collection, processing, and distribution ensure biospecimens are of the highest quality for a broad range of experimental approaches. Currently, NCRAD banks samples from 91 studies representing over 135,000 unique, well-characterized participants, and has distributed over 440,000 aliquots to more than 300 researchers. Data from NCRAD-supported studies have contributed to over 1100 publications and numerous key discoveries in Alzheimer's disease and related dementias (ADRD) genetics and biomarkers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Centralized Biobanking for ADRD Research&lt;/b&gt;: National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) supports over 90 National Institute on Aging (NIA) -funded studies by providing standardized, high-quality biospecimens and longitudinal sample collections, enabling reproducible and scalable research into Alzheimer's disease and related dementias (ADRD).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Enabling Genetic Discovery and Functional Genomics&lt;/b&gt;: NCRAD partnerships with numerous research initiatives has facilitated major advances in gene discovery, while also supporting downstream functional studies using induced pluripotent stem cells (iPSCs), transcriptomics, and &lt;i&gt;post mortem&lt;/i&gt; brain tissue.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Rigorous QA/QC and Automation Infrastructure&lt;/b&gt;: NCRAD employs comprehensive quality assurance/quality control (QA/QC) systems and cutting-edge automation—including robotic liquid handling, automated nucleic acid extraction, and ultra-low temperature storage—to ensure biospecimen integrity and reduce preanalytical variability.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Unique Sample Distribution and Data Sharing Model&lt;/b&gt;: NCRAD's blinded sample distribution system and emphasis on returning data to public repositories ensure broad research access, maximize scientific output, and promote transparency and reproducibility.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;C","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}