Alzheimer's & Dementia最新文献

{"title":"Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker-guided diagnostics","authors":"Hyemin Jang, Daeun Shin, Heejin Yoo, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Theresa A. Day, Eun Hye Lee, Jihwan Yun, Duk L Na, Hee Jin Kim, Sung Hoon Kang, Ko Woon Kim, Si Eun Kim, Yeo Jin Kim, Yeshin Kim, Jaeho Kim, Chi-Hun Kim, Min Young Chun, Na Yeon Jung, Soo Hyun Cho, Jun Pyo Kim, Sang Won Seo","doi":"10.1002/alz.14526","DOIUrl":"https://doi.org/10.1002/alz.14526","url":null,"abstract":"This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"25 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124330","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 Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study","authors":"Nicholas J. Ashton, Ashvini Keshavan, Wagner S. Brum, Ulf Andreasson, Burak Arslan, Mathias Droescher, Stefan Barghorn, Jeroen Vanbrabant, Charlotte Lambrechts, Maxime Van Loo, Erik Stoops, Shweta Iyengar, HaYeun Ji, Xiaomei Xu, Alex Forrest-Hay, Bingqing Zhang, Yuling Luo, Andreas Jeromin, Manu Vandijck, Nathalie Le Bastard, Hartmuth Kolb, Gallen Triana-Baltzer, Divya Bali, Shorena Janelidze, Shieh-Yueh Yang, Catherine Demos, Daniel Romero, George Sigal, Jacob Wohlstadter, Kishore Malyavantham, Meenakshi Khare, Alexander Jethwa, Laura Stoeckl, Johan Gobom, Przemysław R. Kac, Fernando Gonzalez-Ortiz, Laia Montoliu-Gaya, Oskar Hansson, Robert A. Rissman, Maria C. Carrillo, Leslie M. Shaw, Kaj Blennow, Jonathan M. Schott, Henrik Zetterberg","doi":"10.1002/alz.14508","DOIUrl":"https://doi.org/10.1002/alz.14508","url":null,"abstract":"The Alzheimer's Association Global Biomarker Standardization Consortium conducted a blinded case–control study to learn which phosphorylated tau (p-tau) assays provide the largest fold-changes in Alzheimer's disease (AD) versus non-AD and show commutability in measuring patient samples and candidate certified reference materials (CRMs).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"19 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124443","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":"Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts.","authors":"Raffaele Cacciaglia, Carles Falcón, Gonzalo Sánchez Benavides, Anna Brugulat-Serrat, Marta Milà Alomà, Marc Suárez Calvet, José Luis Molinuevo, Karine Fauria, Carolina Minguillón, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Kaj Blennow, Henrik Zetterberg, Luigi Lorenzini, Alle Meije Wink, Silvia Ingala, Frederik Barkhof, Craig W Ritchie, Juan Domingo Gispert","doi":"10.1002/alz.14415","DOIUrl":"https://doi.org/10.1002/alz.14415","url":null,"abstract":"<p><strong>Introduction: </strong>Identifying the link between early Alzheimer's disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals.</p><p><strong>Methods: </strong>We used longitudinal voxel-based morphometry (VBM) in combination with hippocampal subfield segmentation. Changes in neuroimaging and cognitive variables were inspected using general linear models (GLMs) adjusting by age, sex, apolipoprotein E (APOE) status, follow-up time, and years of education.</p><p><strong>Results: </strong>In both cohorts, baseline CSF amyloid beta (Aβ) biomarkers significantly predicted medial temporal lobe (MTL) atrophy rates and episodic memory (EM) decline independently of CSF phosphorylated tau (p-tau).</p><p><strong>Discussion: </strong>Our data suggest that soluble Aβ dyshomeostasis triggers MTL longitudinal atrophy and EM decline independently of CSF p-tau. Our data underscore the need for secondary preventive strategies at the earliest stages of the AD pathological cascade.</p><p><strong>Highlights: </strong>We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p-tau. Our results underscore the importance of undertaking Alzheimer's preclinical trials.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":"e14415"},"PeriodicalIF":13.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078409","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":"Hippocampal neuronal loss and cognitive decline in LATE-NC and ADNC among community-dwelling older persons","authors":"Sonal Agrawal, Lei Yu, Sue E. Leurgans, Sukriti Nag, Lisa L Barnes, David A Bennett, Julie A Schneider","doi":"10.1002/alz.14500","DOIUrl":"https://doi.org/10.1002/alz.14500","url":null,"abstract":"This study investigates the inter-related roles of hippocampal neuronal loss (HNL), limbic-predominant age-related TAR-DNA binding protein of 43 kDa (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and Alzheimer's disease neuropathologic changes (ADNC) on cognitive decline.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"124 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056503","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":"Dual sensory impairment: Global prevalence, future projections, and its association with cognitive decline","authors":"Brian Sheng Yep Yeo, Esther Yanxin Gao, Benjamin Kye Jyn Tan, Benedict Ding Chao Ong, Ryan Wei Yang Cho, Chee Yit Lim, Ryan Eyn Kidd Man, Eva K. Fenwick, Preeti Gupta, Christopher Li-Hsian Chen, Samuel Teong Huang Chew, Neville Wei Yang Teo, Song Tar Toh, Jia Hui Ng, Vanessa Yee Jueen Tan, Ecosse L. Lamoureux","doi":"10.1002/alz.14465","DOIUrl":"https://doi.org/10.1002/alz.14465","url":null,"abstract":"There is rising public health concern surrounding dual sensory impairment (DSI), or comorbid hearing and vision impairments. Its global prevalence and the magnitude of its association with cognitive decline (CD) is unclear. Three databases were searched for epidemiological studies examining DSI prevalence or its association with CD. Independent reviewers selected studies, extracted data, and evaluated bias. Random-effects meta-analyses were performed. Projections were estimated using United Nations data. The population attributable fraction of DSI-associated CD was calculated. Among 43 studies with 5,246,796 participants, clinically assessed DSI prevalence was 5.50% (95% confidence interval [CI] = 2.88%–10.26%), with regional/ethnic/age variations. DSI prevalence is projected to increase by 27.2% from 2025 to 2050. Approximately 59.83% (95%CI = 41.03–76.12) of DSI patients had cognitive impairment. Baseline DSI was associated with incident CD (odds ratio [OR] = 1.72, 95%CI = 1.37–2.15). Globally, 3.81% (95%CI = 1.05–10.55) of incident CD may be attributed to DSI. DSI is globally prevalent, growing, and associated with CD, highlighting the need for better health policy and resource allocation.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"60 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056544","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":"Plasma p‐tau217 and p‐tau217/Aβ1‐42 are effective biomarkers for identifying CSF‐ and PET imaging‐diagnosed Alzheimer's disease: Insights for research and clinical practice","authors":"Xiaomei Zhong, Qiang Wang, Mingfeng Yang, Gaohong Lin, Kexin Yao, Zhangying Wu, Danyan Xu, Huarong Zhou, Ben Chen, Haishan Shi, Min Zhang, Xiaolei Shi, Yijie Zeng, Jingyi Lao, Shuang Liang, JiaFu Li, Qin Liu, Huanmin Liu, Yunheng Chen, Yicheng Lin, Cong Ouyang, Jieqin Lv, Xiang Liang, Yuwang Cheng, Pengcheng Ran, Baoying Gong, Bin Zhang, Jianwen Guo, Hong Zhang, Sen Liu, Jihui Zhang, Haiying Liu, Yuping Ning","doi":"10.1002/alz.14536","DOIUrl":"https://doi.org/10.1002/alz.14536","url":null,"abstract":"INTRODUCTIONWith the advancement of disease‐modifying therapies for Alzheimer's disease (AD), validating plasma biomarkers against cerebrospinal fluid (CSF) and positron emission tomography (PET) standards is crucial in both research and real‐world settings.METHODSWe measured plasma phosphorylated tau (p‐tau)217, p‐tau181, amyloid beta (Aβ)1‐40, Aβ1‐42, and neurofilament light chain in research and real‐world cohorts. Participants were categorized by brain amyloid status using US Food and Drug Administration/European Medicines Agency–approved CSF or PET methods.RESULTSPlasma p‐tau217 and p‐tau217/Aβ1‐42 demonstrated superior accuracy in detecting brain amyloid pathologies, with area under the curve from 0.94 to 0.97 in all cohorts. Specificity was lower in the real‐world cohort but improved significantly by integrating demographic and clinical factors, aligning performance with research cohorts. Additionally, plasma biomarkers exhibited strong correlations with their CSF counterparts and PET standardized uptake value ratios, with significant associations in amyloid‐positive participants.DISCUSSIONPlasma p‐tau217 and p‐tau217/Aβ1‐42 are effective diagnostic tools. However, patient demographics, apolipoprotein E ε4 status, and cognitive condition must be considered to improve specificity in the clinical practice.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>Plasma phosphorylated tau (p‐tau)217 and p‐tau217/amyloid beta (Aβ)1‐42 demonstrated exceptional accuracy (area under the curve: 0.94–0.97) in detecting brain amyloid pathologies across both research (Southern China Aging Brain Initiative [SCABI]‐1, SCABI‐2) and real‐world clinical practice (RCP) cohorts.</jats:list-item> <jats:list-item>Incorporating patient‐specific factors (sex, age, apolipoprotein E ε4, cognitive status) improved diagnostic specificity in the clinical RCP cohort, aligning its performance with that of research cohorts.</jats:list-item> <jats:list-item>Plasma biomarkers, particularly p‐tau217 and their ratios, showed robust correlations with cerebrospinal fluid biomarkers and positron emission tomography amyloid standardized uptake value ratios, underscoring their value as non‐invasive diagnostic alternatives.</jats:list-item> <jats:list-item>Plasma p‐tau217 and p‐tau217/Aβ1‐42 proved highly effective in diagnosing amyloid burden, offering a practical solution to bridge research advancements with real‐world clinical practice.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"23 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056294","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":"Biomarker treatment effects in two phase 3 trials of gantenerumab","authors":"Tobias Bittner, Matteo Tonietto, Gregory Klein, Anton Belusov, Vittorio Illiano, Nicola Voyle, Paul Delmar, Marzia A. Scelsi, Susanna Gobbi, Erica Silvestri, Muhamed Barakovic, Antonio Napolitano, Christopher Galli, Maryam Abaei, Kaj Blennow, Frederik Barkhof","doi":"10.1002/alz.14414","DOIUrl":"https://doi.org/10.1002/alz.14414","url":null,"abstract":"We report biomarker treatment effects in the GRADUATE I and II phase 3 studies of gantenerumab in early Alzheimer's disease (AD).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"26 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056958","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":"Predicting conversion in cognitively normal and mild cognitive impairment individuals with machine learning: Is the CSF status still relevant?","authors":"Mirella Russo, Davide Nardini, Sara Melchiorre, Consuelo Ciprietti, Gaetano Polito, Miriam Punzi, Fedele Dono, Matteo Santilli, Astrid Thomas, Stefano L. Sensi","doi":"10.1002/alz.14398","DOIUrl":"https://doi.org/10.1002/alz.14398","url":null,"abstract":"Machine learning (ML) helps diagnose the mild cognitive impairment–Alzheimer's disease (MCI-AD) spectrum. However, ML is fed with data unavailable in standard clinical practice. Thus, we tested a novel multi-step ML approach to predict cognitive worsening.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"29 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056501","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":"Cranial bone maneuver ameliorates Alzheimer's disease pathology via enhancing meningeal lymphatic drainage function","authors":"Xuan Lu, Shanshan Bai, Lu Feng, Xu Yan, Yuejun Lin, Junzhe Huang, Xulin Liao, Haixing Wang, Linlong Li, Zhengmeng Yang, Leo Yik Chun Yan, Boguang Yang, Ming Wang, Jiakang Jin, Zhixian Zong, Zhaowei Jiang, Chuiguo Huang, Chaoran Liu, Xiaoting Zhang, Han Su, Yaofeng Wang, Wayne Yuk-Wai Lee, Xiaohua Jiang, Micky D. Tortorella, Sien Lin, Ho Ko, Gang Li","doi":"10.1002/alz.14518","DOIUrl":"https://doi.org/10.1002/alz.14518","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Recent research highlights meningeal lymphatics as key regulators in neurological diseases, suggesting that enhancing their drainage function could be a potential therapeutic strategy for AD. Our proof-of-concept study demonstrated that cranial bone transport can improve meningeal lymphatic drainage function and promote ischemic stroke recovery.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"419 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056504","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":"Plasma proteomic characterization of motoric cognitive risk and mild cognitive impairment","authors":"Gabriela T. Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J. Sullivan, Adrienne Tin, B. Gwen Windham, Rebecca F. Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A. Walker","doi":"10.1002/alz.14429","DOIUrl":"https://doi.org/10.1002/alz.14429","url":null,"abstract":"Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"10 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056749","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}