Alzheimer's & Dementia最新文献

{"title":"Baseline characteristics of the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER): Successful enrollment of a diverse clinical trial cohort at risk for cognitive decline","authors":"Rachel A. Whitmer,&nbsp;Laura D. Baker,&nbsp;Maria C. Carrillo,&nbsp;Heather M. Snyder,&nbsp;MaryJo L. Cleveland,&nbsp;Darren R. Gitelman,&nbsp;Miia Kivipelto,&nbsp;Xiaoyan I. Leng,&nbsp;Laura Lovato,&nbsp;Kathryn V. Papp,&nbsp;Valory N. Pavlik,&nbsp;Stephen P. Salloway,&nbsp;Christy C. Tangney,&nbsp;Sarah Tomaszewski Farias,&nbsp;Jeff D. Williamson,&nbsp;Sharon Wilmoth,&nbsp;Nancy Woolard,&nbsp;Melissa Yu,&nbsp;Mark Andrew Espeland,&nbsp;for the U.S. POINTER Study Group","doi":"10.1002/alz.70351","DOIUrl":"https://doi.org/10.1002/alz.70351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year randomized controlled trial of two lifestyle interventions in 2111 older adults at increased risk for cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Sociodemographic and clinical characteristics and rates of ancillary study participation were described with means and frequencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>U.S. POINTER successfully enrolled a cohort, ages 60–79 years, which was ethno-racially inclusive (&gt;30% individuals from groups often under-represented in clinical trials with cognitive outcomes) and 18% residing in neighborhoods with moderate or high levels of socioeconomic deprivation. Enrollees were cognitively intact but at increased risk for cognitive decline. Participation in ancillary studies (overall 73%) was uniformly high across sociodemographic groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The trial cohort meets study goals and provides a basis for assessing multidomain lifestyle intervention effects on cognitive function and other health outcomes that will generalize to large portions of the at-risk US populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CLINICALTRIALS.GOV IDENTIFIER</h3>\u0000 \u0000 <p>NCT00017953.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) enrolled individuals at enhanced risk for cognitive decline.</li>\u0000 \u0000 <li>Efforts to engage socio-demographically representative individuals were successful.</li>\u0000 \u0000 <li>Four ancillary studies with high rate of recruitment extend scientific impact.</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.70351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472926","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 use and reporting of neurofilament quantification in neurological disorders: A global overview","authors":"Constance Delaby,&nbsp;Aurélie Ladang,&nbsp;Jose Martinez-Yriarte,&nbsp;Chiara Zecca,&nbsp;Giancarlo Logroscino,&nbsp;Peter Körtvelyessy,&nbsp;Hayrettin Tumani,&nbsp;Piero Parchi,&nbsp;Isabelle Quadrio,&nbsp;Melanie Hart,&nbsp;Dorte Aalund Olsen,&nbsp;Daniel Alcolea,&nbsp;Kaj Blennow,&nbsp;Juan Fortea,&nbsp;Alberto Lleo,&nbsp;Alicia Algeciras-Schimnich,&nbsp;Xavier Ayrignac,&nbsp;Aurélie Bedel,&nbsp;Gustavo A. A. Santos,&nbsp;Wyllians Borelli,&nbsp;Elodie Bouaziz-Amar,&nbsp;Inês Baldeiras,&nbsp;Edith Bigot-Corbel,&nbsp;Maria Bjerke,&nbsp;Mercedes Carretero Perez,&nbsp;Tiziana Casoli,&nbsp;Tinatin Chabrashvili,&nbsp;Miles D. Chapman,&nbsp;Jessica Cusato,&nbsp;Erdinc Dursun,&nbsp;Anthony Fourier,&nbsp;Daniela Galimberti,&nbsp;Duygu Gezen-Ak,&nbsp;Brian A. Gordon,&nbsp;Julien Gouju,&nbsp;Silvia de las Heras Florez,&nbsp;Juanjo Hernandez Sanchez,&nbsp;Marina Herwerth,&nbsp;Daniele Imperiale,&nbsp;Flora Kaczorowski,&nbsp;Kensaku Kasuga,&nbsp;Ashvini Keshavan,&nbsp;Michael Khalil,&nbsp;Jens Kuhle,&nbsp;Christoph Leithner,&nbsp;Piotr Lewczuk,&nbsp;Franck Letournel,&nbsp;Magda Tsolaki,&nbsp;Guido Maria Giuffrè,&nbsp;Marie-Céline Blanc,&nbsp;Barbara Mroczko,&nbsp;Jose Enrique Martínez Rodríguez,&nbsp;Giulia Musso,&nbsp;Agnieszka Kulczynska-Przybik,&nbsp;Léonor Nogueira,&nbsp;Claire Paquet,&nbsp;Simone Baiardi,&nbsp;Lorenzo Gaetani,&nbsp;Lucilla Parnetti,&nbsp;Raquel Perez Garay,&nbsp;Koen Poesen,&nbsp;Muriel Quillard-Muraine,&nbsp;Enrique Rodriguez Borja,&nbsp;Susanna Schraen,&nbsp;Daniela Terracciano,&nbsp;Franziska Bachhuber,&nbsp;Steffen Halbgebauer,&nbsp;Socrates Tzartos,&nbsp;John Tzartos,&nbsp;Nadine Unterwalder,&nbsp;Lisa Vermunt,&nbsp;Cheryl L. Wellington,&nbsp;Henrik Zetterberg,&nbsp;Charlotte Teunissen,&nbsp;Sylvain Lehmann","doi":"10.1002/alz.70343","DOIUrl":"https://doi.org/10.1002/alz.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Neurofilament light chain (NfL) quantification aids in diagnosing and predicting neurological disorders, but clinical and laboratory practices vary across centers. Differences in result interpretation and reporting further challenge test commutability. This study aimed to review the global analytical and post-analytical methods used for NfL measurement in routine clinical practice across different contexts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We established an international working group (WG) and distributed a survey to its members to gather information on context of use (COU), (pre) analytical methods, cutoff usage, as well as the interpretation and reporting of NfL measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among the centers, 63% measured NfL in cerebrospinal fluid (CSF), 87% in blood, and 53% in both. COU was widespread, with 50% defining pathological cutoffs based on publications and 42% considering age. Reporting was primarily done through numeric results (95%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Harmonizing cutoffs, reporting, and interpretation across various clinical contexts will facilitate the incorporation of this biomarker into routine clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Unique international overview of current analytical and post-analytical methods for neurofilament light chain (NfL) measurement in routine clinical practice.</li>\u0000 \u0000 <li>Tailored sheets for each neurological application.</li>\u0000 \u0000 <li>Strategies to harmonize cutoffs, reporting, and interpretation of NfL's measurement.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367230","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":"Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias: An international multi-center study","authors":"James D. Doecke,&nbsp;Giovanni Bellomo,&nbsp;Lisa Vermunt,&nbsp;Daniel Alcolea,&nbsp;Steffen Halbgebauer,&nbsp;Sjors in ’t Veld,&nbsp;Niklas Mattsson-Carlgren,&nbsp;Katerina Veverova,&nbsp;Christopher J. Fowler,&nbsp;Lynn Boonkamp,&nbsp;Isabel M. Houtkamp,&nbsp;Marleen Koel-Simmerlink,&nbsp;Inge M. W. Verberk,&nbsp;Lorenzo Gaetani,&nbsp;Andrea Toja,&nbsp;Anna Lidia Wojdała,&nbsp;Juan Fortea,&nbsp;Yolande Pijnenburg,&nbsp;Afina Lemstra,&nbsp;Wiesje van der Flier,&nbsp;Jakub Hort,&nbsp;Markus Otto,&nbsp;Oskar Hansson,&nbsp;Lucilla Parnetti,&nbsp;Colin L. Masters,&nbsp;Alberto Lleó,&nbsp;Armand González-Escalante,&nbsp;José Contador,&nbsp;Marc Suárez-Calvet,&nbsp;Aida Fernández-Lebrero,&nbsp;Albert Puig-Pijoan,&nbsp;Paula Ortiz-Romero,&nbsp;Esther Jiménez-Moyano,&nbsp;Carolina Minguillón,&nbsp;Marta del Campo,&nbsp;Charlotte Teunissen","doi":"10.1002/alz.14573","DOIUrl":"https://doi.org/10.1002/alz.14573","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Plasma samples (<i>n</i> = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrospinal fluid biomarkers or amyloid positron emission tomography. Validations were performed in three separate cohorts via single and dual cut-off models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>p-tau181 showed the best area under the curve value to separate AD from frontotemporal dementia, controls, and Aβ– dementia with Lewy bodies. However, this discriminative power could not be reproduced by applying pre-defined cut-offs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>p-tau181 was the best single plasma marker for detecting AD at any stage. Specific cut-offs are needed to maximize diagnostic performances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Phosphorylated tau (p-tau)181 provided a clear differentiation between controls and Alzheimer's disease (AD) participants, with evidence of increased levels in the preclinical stage of AD.</li>\u0000 \u0000 <li>Plasma biomarkers demonstrated that when amyloid co-pathology is removed from dementia with Lewy bodies (DLB), only glial fibrillary acidic protein and neurofilament light chain remain to predict DLB.</li>\u0000 \u0000 <li>Given the low prevalence of amyloid co-pathology in frontotemporal dementia (FTD), p-tau181 and its ratio with amyloid beta 42 are strong biomarkers to differentiate FTD from 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":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367284","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":"TMEM59 deficiency activates chaperone-mediated autophagy and ameliorates disease-like pathologies in tauopathy model mice","authors":"Naizhen Zheng,&nbsp;Zijie Wang,&nbsp;Jing Cao,&nbsp;Kun Li,&nbsp;Hui Xu,&nbsp;Jinghui Wang,&nbsp;Lingliang Zhang,&nbsp;Jian Meng,&nbsp;Ziqian Tang,&nbsp;Hong Luo,&nbsp;Hao Sun,&nbsp;Xian Zhang,&nbsp;Yun-wu Zhang","doi":"10.1002/alz.70369","DOIUrl":"https://doi.org/10.1002/alz.70369","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Tauopathy is characterized by the pathology of tau deposits in the brain. Transmembrane protein 59 (TMEM59) is correlated with Alzheimer's disease (AD), the most common type of tauopathy. However, whether and how TMEM59 regulates tau pathology remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed TMEM59 levels in the brains of AD patients and the tau^P301S transgenic (PS19) mice, evaluated behaviors and tauopathy-related pathologies in PS19 mice with TMEM59 haploinsufficiency, and studied the regulation of TMEM59 on chaperone-mediated autophagy (CMA) using biochemical analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>TMEM59 levels increased in the brains of AD patients and PS19 mice at pathological stages. TMEM59 haploinsufficiency attenuated cognitive deficits and disease-related pathologies in PS19 mice. TMEM59 deficiency promoted lysosome-associated membrane protein type 2A levels and CMA activity, whereas TMEM59 overexpression had the opposite effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our study identifies an important role of TMEM59 in regulating CMA and reveals the potential of targeting TMEM59 for tauopathy intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Transmembrane protein 59 (TMEM59) levels increase in the brains of Alzheimer's disease patients and the tau^P301S transgenic (PS19) tauopathy model mice at pathological stages.</li>\u0000 \u0000 <li>TMEM59 haploinsufficiency attenuates cognitive deficits, neurodegeneration, synapse dysfunction, gliosis, neuroinflammation, and tau pathology in PS19 mice.</li>\u0000 \u0000 <li>TMEM59 interacts with lysosome-associated membrane protein type 2A and heat-shock cognate 71 kDa and regulates chaperone-mediated autophagy.</li>\u0000 \u0000 <li>TMEM59 may serve as a therapeutic target for tauopathy.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367397","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":"Brain tissue electrical conductivity as a promising biomarker for dementia assessment using MRI","authors":"Jiayue Chu,&nbsp;Junye Yao,&nbsp;Zhenghao Li,&nbsp;Jun Li,&nbsp;Yuyao Zhang,&nbsp;Chunlei Liu,&nbsp;Hongjian He,&nbsp;Binyin Li,&nbsp;Hongjiang Wei","doi":"10.1002/alz.70270","DOIUrl":"https://doi.org/10.1002/alz.70270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Dementia, particularly Alzheimer's disease, involves cognitive decline linked to amyloid beta (Aβ) and tau protein aggregation. Magnetic resonance imaging (MRI)-based brain tissue conductivity, which increases in dementia, may serve as a non-invasive biomarker for protein aggregation. We investigate the relationship between MRI-based brain electrical conductivity, protein aggregation, cognition, and gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Brain conductivity maps were reconstructed and correlated with PET protein signals, cognitive performance, and plasma protein levels. The diagnostic potential of conductivity for dementia was assessed, and transcriptomic analysis using the Allen Human Brain Atlas elucidated the underlying biological processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Increased brain conductivity was associated with Aβ and tau aggregation in specific brain regions, cognitive decline, and plasma protein levels. Conductivity also improved dementia discrimination performance, and higher gene expression related to ion transport, cellular development, and signaling pathways was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Brain electrical conductivity shows promise as a biomarker for dementia, correlating with protein aggregation and relevant cellular processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Brain tissue conductivity correlates with Aβ and tau aggregation in dementia.</li>\u0000 \u0000 <li>Brain tissue conductivity correlates with cognitive scores and GMV.</li>\u0000 \u0000 <li>CSF conductivity correlates with plasma protein levels.</li>\u0000 \u0000 <li>Combining conductivity with GMV improves dementia diagnosis accuracy.</li>\u0000 \u0000 <li>Gene expression in ion processes, cell development, and signaling links to conductivity.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367396","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":"Return of research results across the Alzheimer's Disease Research Centers network","authors":"Annalise Rahman-Filipiak,&nbsp;Nathaniel A. Chin,&nbsp;Haley Kohl,&nbsp;Jonathan M. Reader,&nbsp;Claire M. Erickson,&nbsp;Bradford C. Dickerson,&nbsp;Neelum T. Aggarwal,&nbsp;Sterling C. Johnson,&nbsp;Elizabeth C. Mormino,&nbsp;Lindsay R. Clark","doi":"10.1002/alz.70418","DOIUrl":"https://doi.org/10.1002/alz.70418","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Consortium for Clarity in Alzheimer's Disease and Related Dementias Through Imaging (CLARiTI) Return of Results Core aims to develop tools and a framework for disclosing individual results at Alzheimer's Disease Research Centers (ADRCs). An understanding of current disclosure practices is necessary to generate this protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>All 37 ADRCs received a survey between January and April 2024; 36 provided valid responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Most ADRCs disclose diagnosis and cognitive results to participants with impairment, and disclosure of biomarker data (e.g., amyloid and tau positron emission tomography) has accelerated since 2019. Though less common, disclosure to unimpaired participants has increased since 2019. Motivators for disclosure include to thank participants, for recruitment/retention, and to help inform health-care decisions. Barriers include limited expertise and infrastructure, concerns about clinical actionability, and risks to participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The ADRC network is invested in sharing research results. While some concerns remain, CLARiTI will critically evaluate a standardized approach to sharing these results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Individual research results disclosure has increased significantly since 2019.</li>\u0000 \u0000 <li>Results are shared more frequently with cognitively unimpaired participants.</li>\u0000 \u0000 <li>Disclosure requires interdisciplinary teams including physicians and psychologists.</li>\u0000 \u0000 <li>Disclosure motivations include enhancing retention and supporting clinical care.</li>\u0000 \u0000 <li>Barriers include limited resources/expertise and potential participant risks.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339251","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 association between poor sleep health and Alzheimer's disease structural neuroimaging biomarkers","authors":"Emma Nolan,&nbsp;Yunyi Sun,&nbsp;Hui Shi,&nbsp;Derek Archer,&nbsp;Arden Perry,&nbsp;Kimberly Pechman,&nbsp;Niranjana Shashikumar,&nbsp;Bennett Landman,&nbsp;Marissa Gogniat,&nbsp;Dandan Liu,&nbsp;Panpan Zhang,&nbsp;Timothy J. Hohman,&nbsp;Angela L. Jefferson,&nbsp;Kelsie M. Full","doi":"10.1002/alz.70364","DOIUrl":"https://doi.org/10.1002/alz.70364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Poor sleep may be a risk factor for neurodegeneration and Alzheimer's disease (AD). Few studies have examined objectively measured sleep with structural neuroimaging measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Vanderbilt Memory and Aging Project participants (<i>N</i> = 407; median age: 70 years) wore ActiGraph accelerometers for 10 days to estimate sleep regularity, timing, efficiency, duration, wake-after-sleep onset, and awakening length. Volume in brain regions of interest (ROIs) and AD signatures were quantified using 3T brain magnetic resonance imaging (MRI). Cross-sectional linear regression models were adjusted for sociodemographic and lifestyle factors, depression, cognitive status, and cardiovascular risk. ROI and McEvoy models were adjusted for total intracranial volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Greater sleep irregularity (<i>β</i>_Hippocampus= −0.12, <i>p</i> = 0.005; <i>β</i>_McEvoy= −0.07, <i>p</i> = 0.024) and longer awakening length (<i>β</i>_Hippocampus= −0.11, <i>p</i> = 0.009; <i>β</i>_Parietal= −0.08, <i>p</i> = 0.012) were associated with smaller volumes in ROIs related to AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>More irregular and fragmented sleep was associated with smaller volume in ROIs vulnerable to AD, indicating a potential link between poor sleep and neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Associations between sleep and brain health are poorly understood.</li>\u0000 \u0000 <li>Gray matter atrophy by irregular sleep may imply Alzheimer's disease (AD) decline.</li>\u0000 \u0000 <li>Increased sleep irregularity is associated with smaller brain region volume.</li>\u0000 \u0000 <li>Sleep disruption, estimated by awakening length, is linked to AD-related brain volume.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339376","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":"Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease","authors":"Jeffrey Cummings,&nbsp;Sharon Cohen,&nbsp;Jennifer Murphy,&nbsp;Holly M. Brothers,&nbsp;Mina Nejati,&nbsp;Fiona Forrestal,&nbsp;Carl de Moor,&nbsp;John O'Gorman,&nbsp;John Harrison,&nbsp;Judith Jaeger,&nbsp;Catherine Jane Mummery,&nbsp;Anton P. Porsteinsson,&nbsp;Michele Potashman,&nbsp;Ying Tian,&nbsp;Lili Yang,&nbsp;Ping He,&nbsp;Samantha Budd Haeberlein","doi":"10.1002/alz.70224","DOIUrl":"https://doi.org/10.1002/alz.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item-level data and the persistence of treatment benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants with early Alzheimer's disease (AD) were stratified by apolipoprotein E (<i>APOE</i>) ε4 status and randomized (1:1:1) to receive low- or high-dose aducanumab, or placebo. Prespecified principal component analyses (PCAs) per the Statistical Analysis Plan were followed by post hoc examination of individual domains/items across all five clinical endpoints. Progression analysis assessed reduction in clinical decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>High-dose aducanumab demonstrated clinically meaningful slowing of progression across clinical endpoints measuring cognition, daily function, and behavioral symptoms. Delay of progression over 18 months was consistent across measures; treatment effects increased over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Across multiple analyses aducanumab slowed cognitive decline, prolonged functional independence, and attenuated behavioral symptoms in participants with early AD. These outcomes comprise the elements of a clinically meaningful response to treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms.</li>\u0000 \u0000 <li>Treatment benefits were observed across subdomains on all five clinical endpoints.</li>\u0000 \u0000 <li>Aducanumab meaningfully slowed disease progression in participants with early 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":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339380","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":"Multimorbidity patterns and blood biomarkers of Alzheimer's disease in community-dwelling cognitively unimpaired older adults","authors":"Alessandra Marengoni,&nbsp;Giulia Grande,&nbsp;Martina Valletta,&nbsp;Caterina Gregorio,&nbsp;Amaia Calderón-Larrañaga,&nbsp;Matilda Dale,&nbsp;Claudia Fredolini,&nbsp;Bengt Winblad,&nbsp;Davide Liborio Vetrano","doi":"10.1002/alz.70411","DOIUrl":"https://doi.org/10.1002/alz.70411","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;Alzheimer's disease (AD) blood biomarkers hold clinical potential but their concentration may vary with somatic conditions.&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 investigated the concentration of six AD blood biomarkers in relation to multimorbidity as disease count and four multimorbidity patterns in 2290 cognitively unimpaired older adults.&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;Levels of phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) increased with increasing number of diseases. In multi-adjusted regressions, compared to individuals without multimorbidity, the anemia/sensory impairment pattern was associated with altered levels of all biomarkers except amyloid beta (Aβ)42/40, GFAP, and total tau (p-tau181: β = 0.18, 95% confidence interval [CI]: 0.08, 0.28; p-tau217: β = 0.11, 95% CI: 0.03, 0.18; NfL: β = 0.14, 95% CI: 0.06, 0.21) and the cardiometabolic/inflammatory pattern was associated with altered levels of all biomarkers except Aβ42/40 and GFAP (p-tau181: β = 0.24, 95% CI: 0.12, 0.36; p-tau217: β = 0.23, 95% CI: 0.14, 0.32; NfL: β = 0.32, 95% CI: 0.23, 0.40; total tau: β = 0.23, 95% CI: 0.07, 0.39). Results remained unchanged after excluding those who developed dementia in 15 years.&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;More diseases and specific multimorbidity patterns altered the levels of several AD blood biomarkers, highlighting caution when using them in adults with complex health profiles.&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;In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;P-tau181, p-tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Results remained unchanged after excluding participants who developed dementia during 15","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339381","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":"Making outcome measures matter: Why should “what matters to people living with dementia” matter to dementia researchers?","authors":"Siobhan T. Reilly,&nbsp;Andrew J. E. Harding","doi":"10.1002/alz.70359","DOIUrl":"https://doi.org/10.1002/alz.70359","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>This article provides an overview of evidence to support a call to action for dementia researchers to ensure that “what matters to people living with dementia” should be at the heart of any decision-making around the choices and design of outcome measures. There have been sufficient reviews observing how the outcome measures that have been used in previous research have not been those that have been valued by people living with dementia or their carers. If researchers continue to use existing measures that are not valued by people living with dementia, they will waste limited research resources by using measures that are not sufficiently sensitive to detect changes that might be attributed to interventions. It is time for researchers to collaborate internationally to ensure that resources are invested in designing and validating new approaches for measurement of psychosocial outcomes for those living with dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Outcome measures that have been used in previous research have not been those that have been valued by people living with dementia or their carers.</li>\u0000 \u0000 <li>Existing outcome measures have been shown not to be fit for purpose and tend to focus on symptom reduction or broad conceptualizations of quality of life.</li>\u0000 \u0000 <li>Dementia researchers will need to collaborate internationally to ensure that resources are invested in designing and validating new approaches for measurement of psychosocial outcomes for those living with dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339382","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}