Alzheimer's & Dementia最新文献

{"title":"Alzheimer's Association Part the Cloud grants $5 million to develop innovative gene targeting treatments","authors":"","doi":"10.1002/alz.70473","DOIUrl":"https://doi.org/10.1002/alz.70473","url":null,"abstract":"<p>Part the Cloud, through the Alzheimer's Association, announces the awarding of grants totaling $5 million to four studies to develop potential therapies for Alzheimer's disease. These grants focus on gene targeting therapies: therapies that change the expression of genes.</p><p>Started by philanthropist Michaela “Mikey” Hoag and the Alzheimer's Association, Part the Cloud is known for its rigorous and robust review process, encouraging other investors to follow on from its initial funding to expand these innovative trials. To date, Part the Cloud–funded studies have garnered more than $1.6 billion in follow-on funding support.</p><p>Part the Cloud provides strategic funding to advance promising investigational Alzheimer's therapies into clinical trials. The treatment targets are varied, which is important given the growing consensus that effective treatment and prevention of Alzheimer's is likely to be a personalized combination of multiple interventions targeting different aspects of the disease.</p><p>The new awardees are the first recipients of the Part the Cloud Translational Gene Targeting Challenge. More than 100 genes are associated with risk for or resistance to the development of Alzheimer's and other dementias. As a result, there is great potential for personalized gene editing and gene-related therapies.</p><p>“With these substantial and targeted awards, research teams will significantly expand the investigation of how genetics can inform personalized treatments for Alzheimer's and other dementias that address each individual's unique biological circumstances,” said Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead.</p><p>“Our Part the Cloud initiative continues its global leadership in seeding a wide-ranging treatment pipeline that drives the field forward toward effective treatments for everyone from all communities and at all stages of the disease. Now more than ever, it is crucial to fund visionary, forward-looking grants like these,” Carrillo said.</p><p>Started in 2012, Part the Cloud is specifically designed to accelerate the translation of findings from the laboratory, through trials, into possible therapies—filling the gap in Alzheimer's drug development by providing essential support for early-phase clinical trials.</p><p>“Alzheimer's and other diseases that cause dementia affect 50 million people worldwide, including over 7 million in the U.S. alone. It affected my family directly, unexpectedly, and brutally, and it might impact yours, too. We must identify and test treatments that can slow, prevent, or reverse the brain cell damage inflicted by these diseases,” said Hoag.</p><p>“I believe that therapies tailored to the genetic underpinnings of Alzheimer's disease and related dementias have very high potential to supercharge the field toward major breakthroughs,” Hoag added. “Part the Cloud has raised nearly $90 million to fund clinical trials with the highest probability of sl","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624391","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":"Cognitive impairment and dementia in Latin American individuals with parkinsonism and Parkinson's disease: A 10/66 Dementia Research Group study","authors":"Nusrat Khan,&nbsp;Micaela María Arruabarrena,&nbsp;Dani J. Kim,&nbsp;Miao Jiang,&nbsp;Juan J. Llibre-Rodriguez,&nbsp;Ana M. Rodriguez-Salgado,&nbsp;Issac Acosta,&nbsp;Ana Luisa Sosa,&nbsp;Daisy Acosta,&nbsp;Ivonne Z. Jimenez-Velasquez,&nbsp;Mariella Guerra,&nbsp;Aquiles Salas,&nbsp;Ricardo López-Contreras,&nbsp;Dhara Santana,&nbsp;Joel Solorzano,&nbsp;Christina Jeyachandran,&nbsp;Heike Hesse,&nbsp;Caroline Tanner,&nbsp;Matthew Prina,&nbsp;Jorge J. Llibre-Guerra","doi":"10.1002/alz.70371","DOIUrl":"https://doi.org/10.1002/alz.70371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study aimed to determine the associations between parkinsonism and Parkinson's disease (PD) with cognitive impairment and dementia in a multi-country cohort in Latin America, using data from the 10/66 Dementia Research Group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This population-based prospective cohort study was conducted in six Latin American countries, including 11,321 participants 65 years of age or older living in urban and rural areas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>At baseline, the prevalence of cognitive impairment in people with parkinsonism and PD was 33% and 26%, respectively. Parkinsonism (odds ratio [OR] 2.2 [95% confidence interval [CI] 1.9–2.6] and PD (OR 1.9 [95% CI 1.4–2.4]) were individually associated with baseline cognitive impairment and incident dementia. The pooled sub-hazard ratios for dementia in fixed-effect meta-analysis were 1.5 (95% CI 1.2–1.9) for parkinsonism and 1.5 (95% CI 1.0–2.2) for PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia. These findings underscore the importance of routine screening for cognitive impairment in individuals with parkinsonism and PD, to facilitate early detection and intervention strategies that mitigate adverse outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The present study is one of the first longitudinal investigations into the association of parkinsonism and Parkinson's disease (PD) with cognitive impairment and dementia incidence in Latin America.</li>\u0000 \u0000 <li>Parkinsonism and PD showed strong cross-sectional associations with cognitive impairment, with consistent estimates across countries, independent of demographic factors.</li>\u0000 \u0000 <li>Parkinsonism and PD were linked to a significantly higher incidence of dementia over a 4-year follow-up period.</li>\u0000 \u0000 <li>Findings emphasize the need for routine cognitive screening in Parkinsonism and PD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624567","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":"Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial","authors":"Austin McCullough,&nbsp;Charles D. Chen,&nbsp;Brian A. Gordon,&nbsp;Nelly Joseph-Mathurin,&nbsp;Clifford R. Jack Jr,&nbsp;Robert Koeppe,&nbsp;Russ Hornbeck,&nbsp;Deborah Koudelis,&nbsp;Nicole S. McKay,&nbsp;Diana A. Hobbs,&nbsp;Shaney Flores,&nbsp;Sarah J. Keefe,&nbsp;Neelum T. Aggarwal,&nbsp;Ricardo F. Allegri,&nbsp;Sarah B. Berman,&nbsp;Thomas Bird,&nbsp;Sandra E. Black,&nbsp;William S. Brooks,&nbsp;Jasmeer P. Chhatwal,&nbsp;Gregory S. Day,&nbsp;Martin R. Farlow,&nbsp;Nick C. Fox,&nbsp;Serge Gauthier,&nbsp;Lawrence S. Honig,&nbsp;Ging-Yuek Hsiung,&nbsp;Mathias Jucker,&nbsp;Johannes Levin,&nbsp;Mario Masellis,&nbsp;Colin Masters,&nbsp;Patricio Chrem Mendez,&nbsp;John M. Ringman,&nbsp;B. Joy Snider,&nbsp;Stephen Salloway,&nbsp;Peter R. Schofield,&nbsp;Hiroyuki Shimada,&nbsp;Kazushi Suzuki,&nbsp;Christopher H. van Dyck,&nbsp;Gregory Klein,&nbsp;David B. Clifford,&nbsp;Carlos Cruchaga,&nbsp;Jason Hassenstab,&nbsp;Yan Li,&nbsp;Eric McDade,&nbsp;Susan Mills,&nbsp;John C. Morris,&nbsp;Richard J. Perrin,&nbsp;Charlene Supnet-Bell,&nbsp;Guoqiao Wang,&nbsp;Chengjie Xiong,&nbsp;Randall J. Bateman,&nbsp;Tammie L. S. Benzinger,&nbsp;for the DIAN-TU Study Team","doi":"10.1002/alz.70347","DOIUrl":"https://doi.org/10.1002/alz.70347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In the DIAN-TU-001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [¹¹C]-Pittsburgh compound-B (PiB) positron emission tomography (PET), [¹⁸F]-fluoro-2-deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Gantenerumab significantly reduced PiB-PET uptake overall and in most regions and showed no changes in FDG-PET or MRI measures. Drug effects were associated with baseline PiB-PET uptake, and the largest effects occurred in medial regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB-PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gantenerumab unevenly decreased Aβ burden as measured by PiB-PET across brain regions.</li>\u0000 \u0000 <li>The strongest decrease in PiB-PET uptake was in basal ganglia and medial frontal structures.</li>\u0000 \u0000 <li>Variable drug effect on Aβ was partly due to the amount of burden present before treatment.</li>\u0000 \u0000 <li>There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624569","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 years of the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD)","authors":"Joshua D. Grill,&nbsp;Margaret D. Mastrolorenzo,&nbsp;Heather M. Snyder,&nbsp;Maria C. Carrillo,&nbsp;Ronald C. Petersen,&nbsp;Paul Aisen,&nbsp;Reisa Sperling,&nbsp;Kedir Hussen,&nbsp;Rema Raman","doi":"10.1002/alz.70441","DOIUrl":"https://doi.org/10.1002/alz.70441","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>First held in 2020, the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD) is a program to train the next generation of Alzheimer's disease (AD) and related dementias (AD/ADRD) clinical trialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>IMPACT-AD includes didactic, workshop, and small group components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>IMPACT-AD has trained 18 alumni–scholars (accepted from 424 applicants), of whom 67% were female. Forty-eight (26%) were the first in their family to attend college. Scholars included individuals from all racial and ethnic groups. Each year, participants demonstrated increased learning about AD/ADRD clinical trials through a pre/post-test model of knowledge assessments. Among those completing annual follow-up surveys, &gt;84% remain in AD/ADRD trials careers, and 80% have experienced career advances or milestones. In the latter group, &gt; 90% indicated that participating in IMPACT-AD contributed to this career growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>IMPACT-AD is a novel educational program that is achieving its goals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Over 5 years, the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD) has trained 188 scholars.</li>\u0000 \u0000 <li>The course has been accessible to a broad range of trainees who were diverse in professional and demographic backgrounds.</li>\u0000 \u0000 <li>Objective assessments indicate that participants gain knowledge through participation.</li>\u0000 \u0000 <li>Eighty-four percent of trainees have remained in Alzheimer's disease and related dementias (ADRD) trials careers.</li>\u0000 \u0000 <li>Eighty percent of alumni have experienced career advances; nearly all indicated that participating in the course contributed to their success.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624568","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":"Educational attainment, electroencephalographic rhythms, cortical structure, and cognitive performance over 2 years in older adults with subjective memory complaints and brain amyloidosis","authors":"Susanna Lopez,&nbsp;Harald Hampel,&nbsp;Claudio Del Percio,&nbsp;Giuseppe Noce,&nbsp;Roberta Lizio,&nbsp;Stefan J. Teipel,&nbsp;Martin Dyrba,&nbsp;Gabriel González-Escamilla,&nbsp;Hovagim Bakardjian,&nbsp;Patrizia Andrea Chiesa,&nbsp;Enrica Cavedo,&nbsp;Andrea Vergallo,&nbsp;Pablo Lemercier,&nbsp;Giuseppe Spinelli,&nbsp;Michel J. Grothe,&nbsp;Marie-Claude Potier,&nbsp;Fabrizio Stocchi,&nbsp;Chiara Coletti,&nbsp;Raffaele Ferri,&nbsp;Matteo Pardini,&nbsp;Marie-Odile Habert,&nbsp;Simone Marziali,&nbsp;Bruno Dubois,&nbsp;Claudio Babiloni,&nbsp;and INSIGHT-preAD study group","doi":"10.1002/alz.70438","DOIUrl":"https://doi.org/10.1002/alz.70438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We investigated whether older adults with subjective memory complaints (SMC) and amyloid-β accumulation may show clinical progression over 2 years, as measured by resting-state electroencephalographic (rsEEG), structural magnetic resonance imaging (sMRI), and cognitive variables, depending on educational attainment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed these markers in 84 SMC participants from INSIGHT-Pre-AD study, grouped by amyloid-β deposition (¹⁸F-florbetapir positron emission tomography) and educational attainment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In amyloid-negative individuals, higher educational attainment was linked to greater posterior rsEEG alpha activity, possibly reflecting neuroprotective effects. Conversely, amyloid-positive individuals with higher educational attainment showed reduced posterior rsEEG alpha rhythms and lower parietal cortical thickness, potentially indicating compensatory mechanisms counteracting early amyloidosis and neurodegeneration. No longitudinal changes were found in either group over 2 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Education had a stable influence on rsEEG, sMRI, and cognitive markers over 2 years in SMC individuals. Longer follow-up periods should be used to monitor brain status with those markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Education, subjective memory complaint (SMC), and brain amyloid-β deposition.</li>\u0000 \u0000 <li>Stable influence of education on resting-state electroencephalographic (rsEEG), structural magnetic resonance imaging (sMRI), and cognitive markers over 2 years.</li>\u0000 \u0000 <li>Compensatory mechanism of education against early amyloidosis and neurodegeneration.</li>\u0000 \u0000 <li>Longer follow-up periods to monitor brain status in SMC older adults with those markers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624389","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":"Associations between mid-life social relationships and the risk of incident dementia: The ARIC study","authors":"Renée C. Groechel,&nbsp;Albert C. Liu,&nbsp;Pamela L. Lutsey,&nbsp;Priya Palta,&nbsp;Anna M. Kucharska-Newton,&nbsp;Silvia Koton,&nbsp;A. Richey Sharrett,&nbsp;Alden L. Gross,&nbsp;Keenan A. Walker,&nbsp;Rebecca F. Gottesman","doi":"10.1002/alz.70365","DOIUrl":"https://doi.org/10.1002/alz.70365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study aimed to assess whether mid-life social relationships are associated with a lower risk of late-life dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (Visit 2;1990–1992). A composite measure, “social relationships,” was generated. Incident dementia cases were identified following Visit 2 through 2019, using ongoing surveillance. Associations between mid-life social relationships and incident dementia were evaluated with Cox proportional-hazard regression models. Formal interaction tests examined whether sex or race modified this association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among 13,070 participants without dementia, those with strong social relationships in mid-life had a lower risk for developing dementia, compared to participants with poor mid-life social relationships. Neither sex nor race significantly modified this association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Stronger mid-life social relationships may have a potentially protective effect on dementia risk. Future studies evaluating psychosocial health at multiple time points in ethnically diverse populations are needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Psychosocial health is a modifiable risk factor for dementia.</li>\u0000 \u0000 <li>Stronger mid-life social relationships are associated with a lower risk of dementia.</li>\u0000 \u0000 <li>Social relationships may have a potentially protective effect on late-life outcomes.</li>\u0000 \u0000 <li>This study leveraged data collected from nearly 20 years of follow-up in 13,070 participants.</li>\u0000 \u0000 <li>Longitudinal data used in this study were captured in a population that is 24% Black.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624390","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":"High-frequency oscillations >250 Hz in people with Down syndrome and associated Alzheimer's disease dementia","authors":"Christos Panagiotis Lisgaras,&nbsp;Sandra Giménez,&nbsp;María Carmona-Iragui,&nbsp;Lucia Maure-Blesa,&nbsp;Esther Blessing,&nbsp;Juan Fortea,&nbsp;Ricardo S. Osorio","doi":"10.1002/alz.70386","DOIUrl":"https://doi.org/10.1002/alz.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs &gt;250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10-20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Fourteen individuals with DS and five age-matched euploid controls were studied, with all DS cases showing HFOs. HFOs emerged before AD dementia and LOMEDS and showed hemispheric lateralization in asymptomatic but not symptomatic AD dementia cases. A trend toward increasing HFO rates with age in DS warrants further confirmation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>HFOs are promising biomarkers that may predict symptomatic AD dementia in adults with DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Wideband polysomnography reveals a new electrical abnormality in DS.</li>\u0000 \u0000 <li>HFOs precede AD dementia in DS.</li>\u0000 \u0000 <li>The occurrence of HFOs in DS is independent of an epilepsy diagnosis.</li>\u0000 \u0000 <li>HFOs showed hemispheric lateralization in asymptomatic DS cases.</li>\u0000 \u0000 <li>A trend of increased HFO rate with advancing age warrants further investigation.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598291","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":"Whispers of memory: How families navigate dementia support beyond the biomedical lens in Nigeria","authors":"Oluwagbemiga Oyinlola,&nbsp;Tamara Sussman,&nbsp;Magnus Mfoafo-M'Carthy,&nbsp;Lawrence Adekunle Adebusoye","doi":"10.1002/alz.70290","DOIUrl":"https://doi.org/10.1002/alz.70290","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;Research on dementia caregiving in Africa often prioritizes biomedical and formal health-care services, overlooking broader family and community-based support networks. Addressing this gap, this study explores when and which support services Yoruba families use and how these services shape their caregiving experiences within the dementia care context.&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;Guided by interpretive phenomenology and Afrocentric principles, we conducted 15 semi-structured family interviews with 52 participants (2–5 per family), alongside persons with dementia. Interviews were audio-recorded, translated, and thematically analyzed.&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;Help seeking often began when behavioral symptoms became overwhelming. Urban families (&lt;i&gt;n&lt;/i&gt; = 11) leaned on hospital services, while rural families (&lt;i&gt;n&lt;/i&gt; = 4) turned to faith-based and traditional healers. Support was appreciated for offering reassurance, though hospital services often lacked cultural sensitivity, and traditional options—while fostering hope—could reinforce stigma.&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;Enhancing dementia awareness and collaboration between medical, spiritual, and traditional systems may improve caregiver experiences and encourage earlier, culturally appropriate interventions.&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;Yoruba families caring for loved ones with dementia do not adhere to rigid care pathways. Instead, they move fluidly between hospitals, religious spaces, and traditional healing practices—not just in search of treatment but to find meaning, reassurance, and continuity with ancestral ways of knowing.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Memory loss is not always seen as a medical condition; it is often interpreted through spiritual, cultural, and communal lenses. Families may turn to faith leaders or elders first, delaying formal care until behaviors become disruptive or socially visible.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Our interpretive phenomenological analysis, grounded in an Afrocentric lens, reveals caregiving as both an expression of love and a weighty responsibility. The ever-present fear of judgment—from within and outside the family—can lead to silence, isolation, and hesitation in seeking biomedical support.&lt;/li&gt;\u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606611","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":"Spotlight on Alzheimer's disease and related dementias research in East Asia","authors":"Weidong Le,&nbsp;Lu Shen,&nbsp;Tengfei Guo,&nbsp;Fang Xie","doi":"10.1002/alz.70479","DOIUrl":"https://doi.org/10.1002/alz.70479","url":null,"abstract":"<p>With a burgeoning dementia burden driven by unique demographic, genetic, and socioeconomic factors of East Asia, the region has made significant investments in understanding disease mechanisms, developing biomarkers, and exploring therapeutic approaches. This collection highlights the current landscape of Alzheimer's disease and related dementias research in East Asia, including region-specific epidemiological insights, advances in plasma biomarkers and neuroimaging, and innovative diagnostic and treatment strategies. Despite progress, challenges such as limited access to advanced imaging, cultural barriers to autopsy, and disparities in healthcare persist.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598755","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":"ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease","authors":"Paula Perez-Corredor,&nbsp;Said Arevalo-Alquichire,&nbsp;Randall C. Mazzarino,&nbsp;Michael O'Hare,&nbsp;Andres F. Muriel-Torres,&nbsp;Guido N. Vacano,&nbsp;Timothy E. Vanderleest,&nbsp;William P. Miller,&nbsp;Lina Pineda-Lopez,&nbsp;Shivani Patel,&nbsp;Robert A. Obar,&nbsp;Nihat Polat,&nbsp;Leo A. Kim,&nbsp;Joseph F. Arboleda-Velasquez,&nbsp;Claudia Marino","doi":"10.1002/alz.70396","DOIUrl":"https://doi.org/10.1002/alz.70396","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;We described a protected case with familial Alzheimer's disease, homozygous for apolipoprotein E3 (APOE3) Christchurch variant (ApoE3Ch), exhibiting low tau protein levels despite genetic predisposition to the disease due to presenilin (PSEN)1-E280A. We reported the loss of interaction between ApoE3Ch and heparan sulfate proteoglycans (HSPGs) as a critical protective pathway. Here, we characterized differential interacting partners for both wild-type and Christchurch variants to identify additional protective mechanisms of ApoE3Ch.&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 performed pull-down of mouse brain lysates using His-tag-ApoE3 recombinant proteins and determined interacting partners of ApoE3 via mass-spectrometry. We then performed in vitro and in vivo assays to validate the top interactors.&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;We found enhanced binding of ApoE3Ch to tau and Dickkopf-1 (Dkk1, a WNT/β-catenin antagonist) that resulted in reduced tau aggregation in vitro. We demonstrated that ApoE3Ch interacts directly with Dkk1 and tau, reducing tau pathology. These findings supported the hypothesis of novel protective effects of direct ApoE3Ch interactions.&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;⁠Apolipoprotein E3 (ApoE3) Christchurch variant (ApoE3Ch) exhibits different protein interaction profiles compared to wild-type ApoE3, as revealed by proteomic analyses and pull-down experiments.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The ApoE3Ch variant alters the protein's interaction with tau, thus affecting its aggregation in a tau biosensor cell assay and the retina of microtubule-associated protein tau (MAPT*P301S) transgenic mice.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;⁠Gene ontology and pathway analyses indicate that ApoE3Ch interactors are associated with brain-related disorders and specific upstream regulators, including MAPT, a gene encoding for tau.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;⁠Protein–protein interaction studies showed increased binding of ApoE3Ch to Dickkopf1 (Dkk1), a Wnt/β-catenin pathway antagonist, as compared to ApoE3WT, thus indicating that multiple protective mechanisms are regulated by the ApoE3Ch variant&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Our study uncovers a novel protective effect of the ApoE3Ch variant against tau pathology, thus proposing new insights into Alzheimer's disease mechanisms and potential therapeutic target","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589929","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}