- Book学术

IF 4 Q1 CLINICAL NEUROLOGY Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-02-24 eCollection Date: 2025-01-01 DOI:10.1002/dad2.70089

Henry Gilreath Stephenson, Tobey J Betthauser, Rebecca Langhough, Erin Jonaitis, Lianlian Du, Carol Van Hulle, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Nathaniel A Chin, Ozioma C Okonkwo, Cynthia M Carlsson, Sanjay Asthana, Sterling C Johnson, Kaj Blennow, Henrik Zetterberg, Barbara B Bendlin

{"title":"Amyloid is associated with accelerated atrophy in cognitively unimpaired individuals.","authors":"Henry Gilreath Stephenson, Tobey J Betthauser, Rebecca Langhough, Erin Jonaitis, Lianlian Du, Carol Van Hulle, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Nathaniel A Chin, Ozioma C Okonkwo, Cynthia M Carlsson, Sanjay Asthana, Sterling C Johnson, Kaj Blennow, Henrik Zetterberg, Barbara B Bendlin","doi":"10.1002/dad2.70089","DOIUrl":null,"url":null,"abstract":"Introduction: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.Methods: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via z-scoring. Linear mixed-effects models tested differences in longitudinal atrophy between A+ and A-T-N- individuals and between A/T subgroups.Results: A+ was associated with worse atrophy within and beyond the medial temporal lobe, even at low levels of p-tau181.Discussion: Neurodegeneration likely begins soon after the onset of abnormal Aβ pathology. Clinical intervention at the earliest signs of Aβ pathology may be needed to mitigate further neurodegeneration.Highlights: An A-T-N- control group was identified using a robust normative approachA+ was associated with accelerated atrophy in cognitively unimpaired individualsAtrophy was observed even at low p-tau181 levels.","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 1","pages":"e70089"},"PeriodicalIF":4.0000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848556/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70089","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

摘要

简介这项研究考察了406名认知功能未受损（CU）个体（平均随访6.670年，最多13次成像检查）的纵向萎缩与基线脑脊液（CSF）淀粉样β（Aβ，A）和磷酸化tau（p-tau，T）生物标志物（Aβ42/40，p-tau181）的关联，以评估A+是否与阿尔茨海默病样萎缩相关，以及这是否取决于p-tau181水平：方法：采用稳健常模方法确定了无异常神经变性（N）的 A-T- CU 组，并通过 z 评分建立了正常年龄相关萎缩模型。线性混合效应模型测试了A+和A-T-N-个体之间以及A/T亚组之间纵向萎缩的差异：结果：即使p-tau181水平较低，A+与颞叶内侧和外侧萎缩程度更严重有关：讨论：神经退行性变可能在异常 Aβ 病变发生后不久就开始了。讨论：神经退行性变可能在 Aβ 出现异常病理变化后不久就开始了，可能需要在 Aβ 病理变化出现最早迹象时进行临床干预，以减轻神经退行性变的进一步发展：采用稳健的常模方法确定了A-T-N-对照组A+与认知功能未受损个体的加速萎缩有关即使在p-tau181水平较低时也能观察到萎缩。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Amyloid is associated with accelerated atrophy in cognitively unimpaired individuals.

Introduction: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.

Methods: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via z-scoring. Linear mixed-effects models tested differences in longitudinal atrophy between A+ and A-T-N- individuals and between A/T subgroups.

Results: A+ was associated with worse atrophy within and beyond the medial temporal lobe, even at low levels of p-tau181.

Discussion: Neurodegeneration likely begins soon after the onset of abnormal Aβ pathology. Clinical intervention at the earliest signs of Aβ pathology may be needed to mitigate further neurodegeneration.

Highlights: An A-T-N- control group was identified using a robust normative approachA+ was associated with accelerated atrophy in cognitively unimpaired individualsAtrophy was observed even at low p-tau181 levels.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.