Alzheimer's & Dementia最新文献

{"title":"Genome‐wide transcriptome analysis of Aβ deposition on PET in a Korean cohort","authors":"Tamina Park, Jiyun Hwang, Shiwei Liu, Soumilee Chaudhuri, Sang Won Han, Dahyun Yi, Min Soo Byun, Yen‐Ning Huang, Thea Rosewood, Gijung Jung, Min Jeong Kim, Hyejin Ahn, Jun‐Young Lee, Yu Kyeong Kim, MinYoung Cho, Paula J. Bice, Hannah Craft, Shannon L. Risacher, Hongyu Gao, Yunlong Liu, SangYun Kim, Young Ho Park, Dong Young Lee, Andrew J. Saykin, Kwangsik Nho","doi":"10.1002/alz.14348","DOIUrl":"https://doi.org/10.1002/alz.14348","url":null,"abstract":"INTRODUCTIONDespite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations.METHODSRNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co‐expression network, gene‐set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography.RESULTSDGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD‐associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell–mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data.DISCUSSIONOur results in a Korean population suggest Aβ deposition‐associated genes are enriched in NK cell–mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort.</jats:list-item> <jats:list-item>Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort.</jats:list-item> <jats:list-item>Gene network modules were associated with Aβ deposition.</jats:list-item> <jats:list-item>Natural killer (NK) cell proportion in blood was associated with Aβ deposition.</jats:list-item> <jats:list-item>Dysregulated genes were related to a NK cell–mediated immunity.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"18 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing polyomic risk to predict Alzheimer's disease using a machine learning model","authors":"Tiffany Ngai, Julian Willett, Mohammad Waqas, Lucas H. Fishbein, Younjung Choi, Georg Hahn, Kristina Mullin, Christoph Lange, Julian Hecker, Rudolph E. Tanzi, Dmitry Prokopenko","doi":"10.1002/alz.14319","DOIUrl":"https://doi.org/10.1002/alz.14319","url":null,"abstract":"INTRODUCTIONAlzheimer's disease (AD) is the most common form of dementia in the elderly. Given that AD neuropathology begins decades before symptoms, there is a dire need for effective screening tools for early detection of AD to facilitate early intervention.METHODSHere, we used tree‐based and deep learning methods to train polyomic prediction models for AD affection status and age at onset, employing genomic, proteomic, metabolomic, and drug use data from UK Biobank. We used SHAP to determine the feature's importance.RESULTSOur best‐performing polyomic model achieved an area under the receiver operating characteristics curve (AUROC) of 0.87. We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides <jats:italic>apolipoprotein E</jats:italic> (<jats:italic>APOE)</jats:italic> alleles. Increasing the number of cases by including “AD‐by‐proxy” cases did not improve AD prediction.DISCUSSIONAmong the four modalities, genomics, and proteomics were the most informative modality based on AUROC (area under the receiver operating characteristic curve). Our data suggest that two blood‐based biomarkers (glial fibrillary acidic protein [GFAP] and CXCL17) may be effective for early presymptomatic prediction of AD.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>We developed a polyomic model to predict AD and age‐at‐onset using omics and medication use data from EHR.</jats:list-item> <jats:list-item>We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides <jats:italic>APOE</jats:italic> alleles.</jats:list-item> <jats:list-item>“AD‐by‐proxy” cases, if used in training, do not improve AD prediction.</jats:list-item> <jats:list-item>Proteomics was the most informative modality overall for affection status and AAO prediction.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"23 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of amyloid and cardiovascular risk with cognition: Findings from KBASE","authors":"Soumilee Chaudhuri, Desarae A. Dempsey, Yen-Ning Huang, Tamina Park, Sha Cao, Evgeny J. Chumin, Hannah Craft, Paul K. Crane, Shubhabrata Mukherjee, Seo-Eun Choi, Phoebe Scollard, Michael Lee, Connie Nakano, Jesse Mez, Emily H. Trittschuh, Brandon S. Klinedinst, Timothy J. Hohman, Jun-Young Lee, Koung Mi Kang, Chul-Ho Sohn, Yu Kyeong Kim, Dahyun Yi, Min Soo Byun, Shannon L. Risacher, Kwangsik Nho, Andrew J. Saykin, Dong Young Lee","doi":"10.1002/alz.14290","DOIUrl":"https://doi.org/10.1002/alz.14290","url":null,"abstract":"Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"8 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Health Equity Scholars Program: Fostering Culturally Competent and Successful Independent Investigators in Alzheimer's Disease and Related Dementia Research","authors":"Hannatu Amaza, Amber Niay, Mai Seng Thao, Joe Strong, Alyssa Arentoft, Vanessa Guzman, Sid E. O'Bryant, Mike Weiner, Mónica Rivera Mindt, Ozioma C. Okonkwo, ","doi":"10.1002/alz.14323","DOIUrl":"https://doi.org/10.1002/alz.14323","url":null,"abstract":"The Health Equity Scholars Program (HESP) addresses the critical need for a diverse, culturally competent workforce to study and treat older adults from underrepresented populations (URPs) with Alzheimer's disease and related dementias (AD/ADRD). The HESP offers tailored mentored training in AD/ADRD research concepts, aiming to develop successful independent researchers. It recruits Scholars from underrepresented backgrounds as well as those passionate about AD/ADRD health equity research.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"18 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global brain activity and its coupling with cerebrospinal fluid flow is related to tau pathology","authors":"Feng Han, JiaQie Lee, Xi Chen, Jacob Ziontz, Tyler Ward, Susan M. Landau, Suzanne L. Baker, Theresa M. Harrison, William J. Jagust","doi":"10.1002/alz.14296","DOIUrl":"https://doi.org/10.1002/alz.14296","url":null,"abstract":"Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting-state functional magnetic resonance imaging (rsfMRI).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"14 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technology that CARES: Enhancing dementia care through everyday technologies","authors":"Andrew M. Kiselica, Greta E Hermann, Michael K. Scullin, Jared F. Benge","doi":"10.1002/alz.14192","DOIUrl":"https://doi.org/10.1002/alz.14192","url":null,"abstract":"<jats:label/>“Everyday technologies” have long been suggested as digital tools to improve life for and enhance care of persons with Alzheimer's disease and related dementias (ADRD). Within this realm, there is a need to balance potential drawbacks of technologies with their ability to positively impact patient and care partner centered outcomes. To facilitate this goal, we endeavored to provide a common language and conceptual structure to understand digital technology use in ADRD care. Specifically, we describe the pathways by which researchers might develop and deploy technology, including via Cognitive offloading, Automation, Remote monitoring, Emotional/social support, and Symptom treatment (CARES). In addition, we highlight emerging issues in technology‐based care research and provide relevant caveats regarding application of digital technologies in the real world. This discussion provides a framework to organize science on the application of technologies to ADRD care in the future.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>“Everyday technologies” have long been suggested as digital tools to improve life for and enhance care of persons with Alzheimer's disease and related dementias (ADRD).</jats:list-item> <jats:list-item>However, the potential benefits of digital technologies must be balanced against their possible drawbacks.</jats:list-item> <jats:list-item>We describe the pathways by which researchers might develop and deploy technology that CARES, including via Cognitive offloading, Automation, Remote monitoring, Emotional/social support, and Symptom treatment.</jats:list-item> <jats:list-item>This discussion provides a framework to organize science on the application of digital technologies to ADRD care in the future.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"127 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dementia risk reduction in the African context: Multi-national implementation of multimodal strategies to promote healthy brain aging in Africa (the Africa-FINGERS project)","authors":"Chinedu T. Udeh-Momoh, Rachel Maina, Udunna C. Anazodo, Rufus Akinyemi, Lukoye Atwoli, Laura Baker, Darina Bassil, Karen Blackmon, Edna Bosire, Gloria Chemutai, Lucia Crivelli, Laz U. Eze, Agustin Ibanez, Dimitra Kafetsouli, Thomas K. Karikari, Linda Khakali, Manasi Kumar, Imre Lengyel, Celeste A. de Jager Loots, Francesca Mangialasche, Sylvia Mbugua, Zul Merali, Michelle Mielke, Cyprian Mostert, Eunice Muthoni, Olivera Nesic-Taylor, Anthony Ngugi, Samuel Nguku, Adesola Ogunniyi, Adedoyin Ogunyemi, Ozioma C. Okonkwo, Njideka Okubadejo, Robert Perneczky, Tunde Peto, Roselyter M. Riang'a, Mansoor Saleh, Shaheen Sayed, Jasmit Shah, Sheena Shah, Alina Solomon, Thomas Thesen, Dominic Trepel, Valentine Ucheagwu, Victor Valcour, Sheila Waa, Tamlyn Watermeyer, Jennifer Yokoyama, Henrik Zetterberg, Miia Kivipelto","doi":"10.1002/alz.14344","DOIUrl":"https://doi.org/10.1002/alz.14344","url":null,"abstract":"Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle-aged population, Africa presents a prime opportunity to implement evidence-based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa-FINGERS program offers an innovative solution, pioneering culturally sensitive, multidomain interventions tailored to the unique challenges of the region. Leveraging insights from landmark global studies such as Worldwide-FINGERS and Alzheimer's Disease Neuroimaging Initiative, the program employs a multideterminant precision prevention framework, grounded in community based systems dynamics. Africa-FINGERS further integrates cutting-edge state-of-the-art multimodal biomarker evaluations tailored to regional contexts, with the goal of advancing brain health and establishing a global standard for dementia prevention. This groundbreaking initiative highlights the potential for scalableand sustainable interventions, thus is poised to transform dementia risk reduction efforts across the continent.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"70 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes","authors":"Anniina Snellman, Jouni Tuisku, Mikko Koivumäki, Saara Wahlroos, Richard Aarnio, Johan Rajander, Mira Karrasch, Laura L. Ekblad, Juha O. Rinne","doi":"10.1002/alz.14327","DOIUrl":"https://doi.org/10.1002/alz.14327","url":null,"abstract":"We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (<i>APOE</i>) ε4 carriers.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"107 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysiological biomarkers of Alzheimer's disease: In vivo evaluation of synaptic dysfunction.","authors":"Francesco Motolese, Raffaele Dubbioso, Federico Ranieri, Vincenzo Di Lazzaro","doi":"10.1002/alz.14341","DOIUrl":"https://doi.org/10.1002/alz.14341","url":null,"abstract":"","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of skilled nursing facility quality on Medicare beneficiaries with dementia: Evidence from vacancies.","authors":"Cyrus M Kosar, Vincent Mor, Amal N Trivedi, Momotazur Rahman","doi":"10.1002/alz.14251","DOIUrl":"10.1002/alz.14251","url":null,"abstract":"<p><strong>Introduction: </strong>People living with dementia are less likely to be admitted to high-rated nursing homes than people without dementia, despite their increased care needs. We investigated the effect of admission to nursing homes with higher staffing ratings on adverse outcomes for individuals with and without dementia post-hospitalization.</p><p><strong>Methods: </strong>Among Traditional Medicare beneficiaries discharged to nursing homes between 2011 and 2017, we examined the relationship between facility staffing star-ratings and short-term readmission and mortality using an instrumental variables approach to account for selection bias. The instrumental variables were the number of nearby vacant beds in high-rated facilities.</p><p><strong>Results: </strong>Admission to a higher-rated nursing home lowered post-discharge mortality risk at 90 days and reduced 30- and 90-day readmission. Point estimates were larger for people with dementia.</p><p><strong>Discussion: </strong>Findings underscore the need for enhancing direct care staffing in nursing homes and addressing access disparities, particularly for individuals with dementia who benefit significantly from high-quality care.</p><p><strong>Highlights: </strong>We assessed how admission to nursing homes with higher staffing ratings impacted outcomes for individuals with and without dementia by exploiting variation in local bed vacancies as a source of quasi-random assignment. For both persons with and without dementia, adjusted short-term mortality and readmission rates were lower among those discharged to nursing homes with higher staffing ratings. Effects were larger for persons with dementia, indicating welfare loss from inequitable access to higher-rated nursing homes. Increasing staffing in nursing homes and reducing disparities for persons with dementia is essential for enhancing both equity and value.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}