Alzheimer's & Dementia最新文献

{"title":"Associations between objective sleep metrics and brain structure in cognitively unimpaired adults: interactions with sex and Alzheimer's biomarkers","authors":"Laura Stankeviciute,&nbsp;Núria Tort-Colet,&nbsp;Ana Fernández-Arcos,&nbsp;Gonzalo Sánchez-Benavides,&nbsp;Carolina Minguillón,&nbsp;Karine Fauria,&nbsp;Sebastian Camillo Holst,&nbsp;Pilar Garcés,&nbsp;Thomas Mueggler,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Álex Iranzo,&nbsp;Marc Suárez-Calvet,&nbsp;Juan Domingo Gispert,&nbsp;José Luis Molinuevo,&nbsp;Oriol Grau-Rivera,&nbsp;for the ALFA Study","doi":"10.1002/alz.70353","DOIUrl":"https://doi.org/10.1002/alz.70353","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sleep disturbances are prevalent in Alzheimer's disease (AD), probably emerging during its preclinical stage. Poor subjective sleep quality is linked to reduced brain volume and cortical thickness (CTh), but associations with objective sleep measures, particularly regarding sex and AD pathology, remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We characterized 171 cognitively unimpaired adults from the ALzheimer and FAmilies (ALFA) Sleep study using actigraphy, MRI, amyloid beta 42/40, and phosphorylated tau at threonine 181 in cerebrospinal fluid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Lower sleep efficiency, higher wake after sleep onset (WASO), and sleep fragmentation were associated with lower CTh in the medial temporal lobe and other regions linked with AD and sleep disruption, even after adjusting for AD biomarkers. Sex and AD biomarkers modified these associations, with longer WASO showing a stronger correlation with lower CTh in females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Disrupted sleep may reduce cortical integrity independently of AD biomarkers, suggesting alternative pathways. Females appear more vulnerable to impaired sleep, and AD pathology may exacerbate AD-related changes in CTh.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Poor sleep efficiency, increased WASO, and sleep fragmentation are associated with reduced CTh in regions vulnerable to early AD, independently of amyloid and tau pathology.</li>\u0000 \u0000 <li>In the presence of AD pathology, this relationship is altered, with A+T+ individuals exhibiting increased CTh associated with sleep disruption.</li>\u0000 \u0000 <li>Sex-specific effects suggest females are more vulnerable to sleep-related cortical thinning.</li>\u0000 \u0000 <li>These findings highlight the potential of targeting sleep as a secondary prevention strategy to preserve brain integrity and mitigate neurodegenerative processes in AD-vulnerable regions.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482205","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":"Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial","authors":"Jeffrey M. Burns,&nbsp;Jill K. Morris,&nbsp;Eric D. Vidoni,&nbsp;Heather M. Wilkins,&nbsp;In-Young Choi,&nbsp;Phil Lee,&nbsp;Suzanne L. Hunt,&nbsp;Jonathan D. Mahnken,&nbsp;William M. Brooks,&nbsp;Rebecca J. Lepping,&nbsp;Aditi Gupta,&nbsp;Russell Esterline,&nbsp;Jan Oscarsson,&nbsp;Russell H. Swerdlow","doi":"10.1002/alz.70416","DOIUrl":"https://doi.org/10.1002/alz.70416","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Due to its metabolic effects, dapagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, holds potential as an Alzheimer's disease (AD) therapeutic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a double-blind, randomized, placebo-controlled, parallel-group, 12-week single-site study to investigate the effect of dapagliflozin in participants with probable AD (Mini-Mental State Examination [MMSE] score 15–26). We planned to enroll 48 participants with 2:1 randomization to 10 mg dapagliflozin once daily (<i>n</i> = 32) versus matching placebo (<i>n</i> = 16). The primary objective was the effect of dapagliflozin on cerebral <i>N</i>-acetylaspartate (NAA). We also assessed safety, glycemic control, body composition, brain metabolism, and cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>There was no change in the primary outcome. There were no significant adverse event differences. Hemoglobin A1c, fat mass, and fat-free lean mass decreased; brain glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may affect the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Dapagliflozin did not alter magnetic resonance spectroscopy <i>N</i>-acetylaspartate (primary outcome) in this exploratory Alzheimer's disease (AD) trial.</li>\u0000 \u0000 <li>Dapagliflozin-induced glucose disposal is sufficient to alter systemic metabolism.</li>\u0000 \u0000 <li>AD patients taking dapagliflozin exhibited metabolic effects seen in diabetics.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482224","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":"Clinical features, biomarker profiles, and neuroimaging characteristics in patients from memory clinic in china: The Shanghai Memory Study","authors":"Jie Wang,&nbsp;Xiaoxi Ma,&nbsp;Jiaying Lu,&nbsp;Jie Wu,&nbsp;Zhenxu Xiao,&nbsp;Huiwei Zhang,&nbsp;Weiqi Bao,&nbsp;Saineng Ding,&nbsp;Li Zheng,&nbsp;Xiaoniu Liang,&nbsp;Yihui Guan,&nbsp;Chuantao Zuo,&nbsp;Ding Ding,&nbsp;Qianhua Zhao,&nbsp;the Shanghai Memory Study (SMS)","doi":"10.1002/alz.70378","DOIUrl":"https://doi.org/10.1002/alz.70378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Despite advances in biomarker assessment, molecular neuroimaging, and disease-modifying therapies for cognitive disorders, China lacks well-characterized clinical cohorts integrating comprehensive clinical assessments and multimodal biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The Shanghai Memory Study (SMS), an ongoing hospital-based cohort, enrolled participants undergoing clinical/neuropsychological assessments, genotyping, multimodal imaging, and biospecimen collection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>From 2012 to 2024, 2001 participants were enrolled: 115 cognitively unimpaired (CU), 938 with mild cognitive impairment (MCI), and 948 with dementia. Positron emission tomography (PET) scan revealed A+/T+ positivity rates of 15.8% in CU, 51.2% in MCI, and 100% in Alzheimer's disease dementia (ADD). Plasma tau phosphorylated at threonine 181 (p-tau181) level increased gradually across the AD continuum. Blood p-tau181 and 18F-Florzolotau PET showed comparable utility for amyloid status identification. In a subcohort of 251 amnestic MCI (aMCI) patients, low Aβ42/Aβ40 and elevated p-tau181 predicted 4.7-year ADD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>By offering an integrated framework, SMS will facilitate the exploration of AD pathogenesis and the understanding of cognitive disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The SMS is an ongoing prospective cohort study based on a memory clinic in China.</li>\u0000 \u0000 <li>The SMS has established a relatively large-scale dataset that includes clinical data, biofluid markers, MRI and PET imaging, and novel biomarkers.</li>\u0000 \u0000 <li>By offering an integrated framework, SMS aims to facilitate the exploration of AD pathogenesis and deepen our understanding of cognitive disorders.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482237","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":"Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease","authors":"Jürgen Germann,&nbsp;Robert S. C. Amaral,&nbsp;Jennifer Tomaszczyk,&nbsp;Kazuaki Yamamoto,&nbsp;Gavin J. B. Elias,&nbsp;Flavia Venetucci Gouveia,&nbsp;Anna Vasilevskaya,&nbsp;Foad Taghdiri,&nbsp;Gabriel A. Devenyi,&nbsp;Tejas Sankar,&nbsp;Jeannie-Marie Leoutsakos,&nbsp;Cynthia A. Munro,&nbsp;Paul B. Rosenberg,&nbsp;Constantine G. Lyketsos,&nbsp;Esther S. Oh,&nbsp;William S. Anderson,&nbsp;Zoltan Mari,&nbsp;Lisa Fosdick,&nbsp;Kristen E. Drake,&nbsp;Steven D. Targum,&nbsp;Jo Cara Pendergrass,&nbsp;Anna Burke,&nbsp;Stephen Salloway,&nbsp;Wael F. Asaad,&nbsp;Francisco A. Ponce,&nbsp;Marwan Sabbagh,&nbsp;David A. Wolk,&nbsp;Gordon Baltuch,&nbsp;Michael S. Okun,&nbsp;Kelly D. Foote,&nbsp;Peter Giacobbe,&nbsp;Mary Pat McAndrews,&nbsp;David F. Tang-Wai,&nbsp;Gwenn S. Smith,&nbsp;M. Carmela Tartaglia,&nbsp;M. Mallar Chakravarty,&nbsp;Andres M. Lozano,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70394","DOIUrl":"https://doi.org/10.1002/alz.70394","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Deep brain stimulation of the fornix (fx-DBS) is being investigated for treatment of Alzheimer's disease (AD). The therapy aims at alleviating memory and cognitive circuit dysfunction. In preclinical models of AD, electrical stimulation of the memory circuit has demonstrated a possible disease-modifying potential. Here we examined changes resulting from fx-DBS in hippocampal atrophy and amyloid accumulation in AD patients with fx-DBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Repeated magnetic resonance imaging and positron emission tomography (PET) images acquired over the course of 12 months were used to assess changes in hippocampal volume in 36 ADvance trial patients compared to 40 matched untreated AD patients from the Alzheimer's Disease Neuroimaging Initiative, and in 10 separate patients with repeated flutemetamol PET and cerebrospinal fluid (CSF) markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We observed a reduction of hippocampal atrophy and amyloid beta (Aβ) PET binding, and an increase in the CSF Aβ/total-tau ratio in DBS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings highlight the potential of fornix deep brain stimulation to modify AD biomarkers and possibly progression in some patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Fornix deep brain stimulation (fx-DBS) is being investigated to treat Alzheimer's disease (AD).</li>\u0000 \u0000 <li>Results show that fx-DBS modifies imaging and cerebrospinal fluid (CSF) markers.</li>\u0000 \u0000 <li>It reduces hippocampal atrophy and increases the amyloid beta/total-tau CSF ratio.</li>\u0000 \u0000 <li>These findings highlight the potential of fx-DBS to modify AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482239","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":"Plasma NfL and GFAP for predicting VCI and related brain changes in community and clinical cohorts","authors":"Sheelakumari Raghavan,&nbsp;Jonathan Graff-Radford,&nbsp;Ekaterina Hofrenning,&nbsp;Angela J. Fought,&nbsp;Robert I. Reid,&nbsp;Michael G. Kamykowski,&nbsp;Alicia Algeciras-Schimnich,&nbsp;B. Gwen Windham,&nbsp;David S. Knopman,&nbsp;Val J. Lowe,&nbsp;Clifford R. Jack Jr,&nbsp;Ronald C. Petersen,&nbsp;Prashanthi Vemuri","doi":"10.1002/alz.70381","DOIUrl":"https://doi.org/10.1002/alz.70381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We investigated the usefulness of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for capturing vascular cognitive impairment (VCI) in the context of amyloidosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using two independent cohorts (<i>n</i> = 1810), we assessed the relationship of plasma NfL and GFAP with (1) vascular brain indices; (2) diagnostic states using the following definitions: vascular versus not (white matter hyperintensity/total intracranial volume ≥ 1.3%), and cognitively impaired (CI) versus cognitively unimpaired (CU) using Clinical Dementia Rating ([CDR] scale ≥ 0.5); and (3) their upstream predictors using structural equation models (SEMs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Plasma NfL and GFAP were associated with vascular brain damage and differed across states (VCI &gt; vascular CU &gt; non-vascular CI &gt; non-vascular CU). In a population-based sample, these biomarkers distinguished vascular CU and VCI from non-vascular CU groups with greater separation in amyloid negative participants. Pathway analyses showed NfL was primarily influenced by systemic/brain vascular health, whereas amyloid contributed to GFAP variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma biomarkers, particularly NfL, capture vascular brain changes and show promise for VCI identification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma NfL and glial fibrillary acidic protein (GFAP) were associated with vascular brain indices.</li>\u0000 \u0000 <li>Plasma biomarkers differed across diagnostic states (VCI &gt; vascular CU &gt; non-vascular CI &gt; non-vascular CU).\u0000</li>\u0000 \u0000 <li>Plasma markers discriminated vascular from non-vascular states with greater separation in Aβ− participants.</li>\u0000 \u0000 <li>NfL was linked to vascular health, while amyloid influenced GFAP variability in the population-based sample.</li>\u0000 \u0000 <li>Future longitudinal frameworks should consider systemic inflammation markers along with these plasma markers to better understand VCID-related brain changes and cognitive decline.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482238","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":"Unmet needs and nursing home placements in Black, Latino, and White people living with dementia","authors":"Jasmine Travers Altizer,&nbsp;Shivani Shenoy,&nbsp;Anisha Balaji,&nbsp;Marissa Bergh,&nbsp;Aasha Raval,&nbsp;Andreina Jimenez","doi":"10.1002/alz.70265","DOIUrl":"https://doi.org/10.1002/alz.70265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Many nursing home (NH) placements are avoidable considering equivalent care is possible in community settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This qualitative descriptive study explored the unmet needs and related barriers that drive avoidable NH placements among Black, Hispanic/Latino, and White persons living with dementia (PLWD). Interviews were conducted with PLWD, family care partners, and NH staff, from two New York NHs along with aging policy experts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> FINDINGS</h3>\u0000 \u0000 <p>Seven distinct themes specific to unmet needs emerged from interviews including (1) assistance with activities of daily living and basic home maintenance; (2) resources and services; (3) treatment-related services; (4) socialization; (5) individual preferences; (6) function of the home (e.g., unaddressed home modification needs); and (7) equipped, available, and supported family. Barriers contributing to unmet needs included awareness, knowledge, availability, affordability, and acceptability of resources, services, and supports.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Strategies to address these unmet needs and improve community-based services may help reduce these NH placements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Many people living with dementia can remain at home with necessary supports.</li>\u0000 \u0000 <li>There is limited paid and unpaid assistance to support people living with dementia.</li>\u0000 \u0000 <li>Navigating the complex landscape of services in the community is challenging.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482241","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":"World Dementia Council Update","authors":"","doi":"10.1002/alz.70414","DOIUrl":"https://doi.org/10.1002/alz.70414","url":null,"abstract":"<p>The Caribbean is a diverse region made up of many different countries, cultures, and languages. And, dementia presents a serious public health challenge across the region as a whole, with projections estimating a 155% increase in cases by 2050. Addressing this rapidly growing issue will require increased attention and coordinated efforts to improve diagnosis, advocacy, and more.</p><p>As a part of its commitment to advancing global efforts on dementia, the World Dementia Council (WDC) recently convened dementia experts to participate in virtual dialogues centered around dementia and the Caribbean. The first dialogue focused on strategies to increase dementia diagnosis and health system preparedness, while the second explored how partners across the region can build policy momentum, raise public awareness, and drive system-level change in response to the Caribbean's rising dementia burden.</p><p>The WDC dialogue on diagnosis and health system preparedness in the Caribbean occurred on April 8, 2025.</p><p>The WDC dialogue on policy, advocacy, and awareness in the Caribbean occurred on April 25, 2025.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367316","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":"Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways","authors":"Joseph Bradley,&nbsp;Cyril Pottier,&nbsp;Eder Lucio da Fonseca,&nbsp;Jiji Thulaseedhara Kurup,&nbsp;Daniel Western,&nbsp;Ciyang Wang,&nbsp;Achal Neupane,&nbsp;Nicholas R. Ray,&nbsp;Melissa Jean-Francois,&nbsp;Muhammad Ali,&nbsp;Jigyasha Timsina,&nbsp;Kristy Bergmann,&nbsp;John Budde,&nbsp;Eden R. Martin,&nbsp;Margaret A. Pericak-Vance,&nbsp;Michael Cuccaro,&nbsp;Adam C. Naj,&nbsp;Brian W. Kunkle,&nbsp;Alzheimer's Disease Genetics Consortium (ADGC), Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight-ADRC),&nbsp;Gerard D. Schellenberg,&nbsp;Victoria Fernandez,&nbsp;Jonathan Haines,&nbsp;John C. Morris,&nbsp;David M. Holtzman,&nbsp;Richard J. Perrin,&nbsp;Christiane Reitz,&nbsp;Gary W. Beecham,&nbsp;Carlos Cruchaga","doi":"10.1002/alz.70377","DOIUrl":"https://doi.org/10.1002/alz.70377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Most genetic studies for Alzheimer's disease (AD) have been focused on late-onset AD (LOAD). There are no large genetic studies on early-onset AD (EOAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed a multi-ancestry (non-Hispanic European, African, and East Asian) genome-wide association study (GWAS) including a total of 7,349 cases and 17,887 control. Cases with age at onset younger than 70 years were included. Sensitivity analysis including cases with onset &lt;65 was performed. Only controls older than 70 were included to decrease the risk of developing LOAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis. By integrating gene-based analysis, expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL), and functional annotations, we nominate eight novel genes that are involved in microglia activation, glutamate production, and signaling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>EOAD, although sharing genes with LOAD, harbors unique genes and pathways that could be used to create better prediction models or target identification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We performed the largest and first multi-ethnic genetic screening for early-onset Alzheimer's disease (AD).</li>\u0000 \u0000 <li>We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis.</li>\u0000 \u0000 <li>The novel genes are implicated microglia activation, glutamate production, and signaling pathways.</li>\u0000 \u0000 <li>EOAD, although sharing many genes with LOAD, harbors unique genes and pathways that could be used to create better prediction models or target identification for this type of AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472930","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":"Voluntary wheel running exercise improves sleep disorder, circadian rhythm disturbance, and neuropathology in an animal model of Alzheimer's disease","authors":"Yiying Hu,&nbsp;Long Niu,&nbsp;Yixin Chen,&nbsp;Huijia Yang,&nbsp;Xinhui Qiu,&nbsp;Fei Jiang,&nbsp;Cong Liu,&nbsp;Huaibin Cai,&nbsp;Weidong Le","doi":"10.1002/alz.70314","DOIUrl":"https://doi.org/10.1002/alz.70314","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 sleep–wake cycle and circadian rhythm disturbances are common in Alzheimer's disease (AD). However, it is not known if exercise has any benefit for the sleep disorders in AD.&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;We conducted a 2-month voluntary wheel running (VWR) exercise (Ex) in an animal model of AD (APP&lt;sup&gt;SWE&lt;/sup&gt;/PS1&lt;sup&gt;dE9&lt;/sup&gt; mice). We assessed behavioral circadian rhythm, sleep structure, circadian clock genes, cognitive function, and neurodegeneration in the suprachiasmatic nucleus (SCN), the hippocampus, and the cortex.&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;After VWR exercise in the AD mice, the rapid eye movement sleep was increased by 89%. The levels of circadian clock genes were significantly changed (brain and muscle arnt-like protein 1 [BMAL1] and retinoic acid receptor-related orphan receptorsα [RORα] reduced by 45.7% and 36.4%, reverse erythroblastosis virusα (REV-ERBα) increased by 119%) in the SCN by immunofluorescence staining, with the mRNA levels were markedly altered (&lt;i&gt;Bmal1&lt;/i&gt; and &lt;i&gt;Rorα&lt;/i&gt; decreased by 57% and 68%, &lt;i&gt;Rev-erbα&lt;/i&gt; elevated by 79%) in the hypothalamus at Zeitgeber Time 1; phospho-tau 231 (p-tau231) was reduced by 35%, whereas vesicular GABA transporter (VGAT) was elevated by 38.7% in the SCN. In addition, ionized calcium binding adapter molecude 1 (Iba1), glial fibrillary acidic protein (GFAP), amyloid β (Aβ), and p-tau231 were significantly reduced in the hippocampus and cortex.&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;Our results demonstrate that VWR exercise improves sleep disorders, cognitive deficits, and neuropathology in AD mice.&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;Voluntary wheel running (VWR) exercise improves the behavioral circadian rhythm disorder and sleep structure disturbance in Alzheimer's disease (AD) mice.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;After VWR exercise, there is a significant change in the expression levels of circadian clock genes, and a remarkable reduction of tau phosphorylation and axonal damage in the γ-aminobutyric acid (GABA)ergic neurons in the suprachiasmatic nucleus (SCN).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The levels of beta-site amyloid precurson protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) are reduced in the hypothalamus after VWR exercise in A","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472858","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":"PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations","authors":"Andrew McVea,&nbsp;Alexandra DiFilippo,&nbsp;Max McLachlan,&nbsp;Brecca Betcher,&nbsp;Matthew Zammit,&nbsp;Tobey J. Betthauser,&nbsp;Alexander Converse,&nbsp;Dhanabalan Murali,&nbsp;Charles Stone,&nbsp;Sigan Hartley,&nbsp;Sterling Johnson,&nbsp;Dana L. Tudorascu,&nbsp;Charles M. Laymon,&nbsp;Ann D. Cohen,&nbsp;Davneet Minhas,&nbsp;Weiquan Luo,&nbsp;Chester Mathis,&nbsp;Patrick J. Lao,&nbsp;Beau Ances,&nbsp;Shahid Zaman,&nbsp;Mark Mapstone,&nbsp;Elizabeth Head,&nbsp;Benjamin L. Handen,&nbsp;Bradley T. Christian,&nbsp;ABC-DS investigators","doi":"10.1002/alz.70357","DOIUrl":"https://doi.org/10.1002/alz.70357","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;Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.&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;Participants with ≥ 3 [C-11]PiB scans (spanning &gt; 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants. Amyloid accumulation was compared using global standardized uptake value ratio (SUVR) for Aβ deposition, with individual growth rates (&lt;i&gt;r&lt;/i&gt;) estimated using the logistic growth model (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mi&gt;U&lt;/mi&gt;\u0000 &lt;mi&gt;V&lt;/mi&gt;\u0000 &lt;mi&gt;R&lt;/mi&gt;\u0000 &lt;mspace&gt;&lt;/mspace&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;(&lt;/mo&gt;\u0000 &lt;mi&gt;t&lt;/mi&gt;\u0000 &lt;mo&gt;)&lt;/mo&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mo&gt;=&lt;/mo&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mi&gt;U&lt;/mi&gt;\u0000 &lt;mi&gt;V&lt;/mi&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;R&lt;/mi&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mi&gt;B&lt;/mi&gt;\u0000 &lt;mi&gt;L&lt;/mi&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;mo&gt;+&lt;/mo&gt;\u0000 &lt;mfrac&gt;\u0000 &lt;mi&gt;K&lt;/mi&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;1&lt;/mn&gt;\u0000 &lt;mo&gt;+&lt;/mo&gt;\u0000 &lt;msup&gt;\u0000 &lt;mi&gt;e&lt;/mi&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;mi&gt;r&lt;/mi&gt;\u0000 &lt;mo&gt;(&lt;/mo&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mi&gt;t&lt;/mi&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;t&lt;/mi&gt;\u0000 &lt;mn&gt;50&lt;/mn&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mo&gt;)&lt;/mo&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/mfrac&gt;\u0000 &lt;/mrow&gt;\u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472927","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}