Sleep Quality and Mechanistic Links to Alzheimer Disease and Related Disorders among older Mexican Americans and Non-Hispanic Whites

项目概要/摘要 临床神经科学最令人兴奋的最新进展之一是建立了一种联系， 阿尔茨海默病及相关痴呆症（ADRD）之间的关系。ADRD患者经常 睡眠质量差/睡眠障碍，越来越多的证据，包括我们的团队，表明穷人 睡眠质量会增加患ADRD风险。这种双向关联对以下方面有着深远的影响： 预防和治疗，但仍存在许多问题。墨西哥裔美国人（MA）代表最快的 在美国，越来越多的族裔群体面临着许多健康差距，包括更大的 与非西班牙裔白人（NHW）相比，代谢/血管风险。最近的证据，虽然有争议， 表明西班牙裔人的主观睡眠问题更大，但这些数据在老年西班牙裔人中缺乏， 尤其是MA，对客观测量的睡眠知之甚少。我们的成本效益和创新研究 将解决其中的许多差距。本提案的总体目标是确定 睡眠质量（客观和主观指标）和认知障碍，包括MA中的ADRD， NHW，并阐明连接这些条件的靶向途径。我们将利用正在进行的健康和 拉丁裔老年人大脑老化（HABLE）研究，以成本效益的方式调查客观测量的睡眠 在500名社区居住的MA和500名NHW中，认知障碍水平（约40%） 轻度认知障碍/ADRD）。HABLE研究具有深入的表型和生物标志物， 代谢/血管健康。此外，所有参与者都将接受脑部MRI检查，部分参与者将接受淀粉样蛋白PET检查。 扫描，经济高效地使我们能够研究神经退行性和血管/炎症途径 与睡眠质量有关。我们建议将这些目标作为HABLE-Dormir辅助研究的一部分： 1)为了描述老年NHW和MA的客观和主观睡眠质量， 2）为了检查睡眠质量与2至3年认知能力下降之间的纵向关联， 3)为了确定睡眠质量与关键机制通路（包括血管和 研究睡眠质量与淀粉样蛋白生物标志物（PET）之间的关系 扫描和血浆A β 40和A β 42）和其他神经变性指标（血浆tau、NFL和 海马萎缩）。我们有一个前所未有的机会，与一个非常有经验的， 多学科小组，进行有史以来第一次全面调查的几个关键途径， MA和NHW可能与睡眠和ADRD相关。了解纵向关联和机制 在老年人中，睡眠和ADRD之间的关系将有助于早期发现和预防ADRD， 服务不足的人口以及所有老年人。

PROJECT SUMMARY/ABSTRACT One of the most exciting recent advances in clinical neuroscience has been the establishment of a connection between sleep and Alzheimer's Disease and Related Dementias (ADRD). Patients with ADRD frequently experience poor sleep quality/disorders and growing evidence, including from our team, suggest that poor sleep quality increase risk of developing ADRD. This bidirectional association has profound implications for prevention and treatment, however many questions remain. Mexican Americans (MAs) represent the fastest growing ethnic group in the U.S. and MAs face numerous health disparities including greater metabolic/vascular risk compared to Non-Hispanic Whites (NHWs). Recent evidence, while controversial, suggests greater subjective sleep problems in Hispanics, but these data are lacking in older Hispanics, especially MAs, and little is known about objectively measured sleep. Our cost-efficient and innovative study will address many of these gaps. The overall objective of this proposal is to determine the association between sleep quality (objective and subjective measures) and cognitive impairment including ADRD among MAs and NHWs, and to elucidate targeted pathways linking these conditions. We will leverage the ongoing Health & Aging Brain among Latino Elders (HABLE) study to cost-efficiently investigate objectively measured sleep among 500 community-dwelling MAs and 500 NHWs across level of cognitive impairment (approximately 40% with Mild Cognitive Impairment/ADRD). The HABLE study has deep phenotyping and biomarkers for metabolic/vascular health. In addition, all participants will have a brain MRI and a subset will have amyloid PET scans, cost-efficiently enabling our investigation of neurodegenerative and vascular/inflammatory pathways associated with sleep quality. We propose to conduct these aims as part of the HABLE-Dormir ancillary study: 1) To characterize objective and subjective sleep quality among older NHWs and MAs across the cognitive spectrum, 2) To examine the longitudinal association between sleep quality and 2 to 3-year cognitive decline, 3) To determine the association between sleep quality and key mechanistic pathways including vascular and inflammation and 4) To investigate the association between sleep quality and biomarkers of amyloid (PET scans and plasma Aβ40 and Aβ42) and other measures of neurodegeneration (plasma tau, NFL, and hippocampal atrophy). We have an unprecedented opportunity, working with a very experienced and multidisciplinary team, to conduct the first-ever comprehensive investigation of several key pathways among MAs and NHWs that may link sleep and ADRD. Understanding the longitudinal association and mechanisms between sleep and ADRD among older MAs will help with the early detection and prevention of ADRD in this underserved population as well as all older adults.