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

项目摘要/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 睡眠与阿尔茨海默病和相关痴呆症(ADRD)之间的关系。经常出现ADRD的患者 睡眠质量差/睡眠障碍的经历和越来越多的证据，包括来自我们团队的证据，表明睡眠质量不佳 睡眠质量会增加患ADRD的风险。这种双向联系具有深远的影响， 然而，预防和治疗仍然存在许多问题。墨西哥裔美国人(MA)是速度最快的 美国和马斯日益增长的种族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， 这表明拉美裔美国人的主观睡眠问题更严重，但这些数据在年长的拉美裔美国人中是缺乏的， 尤其是MAS，对客观测量的睡眠知之甚少。我们具有成本效益和创新性的研究 将填补其中的许多差距。该提案的总体目标是确定两者之间的关联 睡眠质量(客观和主观测量)和包括ADRD在内的认知损害 NHW，并阐明连接这些条件的靶向通路。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，以经济高效地调查客观测量的睡眠 在500个社区居住的MA和500个NHW中，认知障碍程度(约40%) 轻度认知障碍(ADRD)。Hable的研究有深刻的表型和生物标记物 代谢/血管健康。此外，所有参与者都将接受脑部核磁共振检查，其中一部分人将接受淀粉样蛋白PET检查 扫描，使我们能够经济高效地研究神经退行性变和血管/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)从认知的角度描述老年卫生工作者和母亲的客观和主观睡眠质量 频谱，2)检查睡眠质量和2到3年认知下降之间的纵向联系， 3)确定睡眠质量与关键机械通路之间的关联，包括血管和 4)研究睡眠质量与淀粉样蛋白生物标志物(PET)的关系 扫描和血浆Aβ40和Aβ42)和其他神经退行性改变的测量(血浆tau、nfl和 海马区萎缩)。我们有一个前所未有的机会，与一位非常有经验和 多学科团队，对以下几个关键途径进行首次全面调查 可能将睡眠和ADRD联系在一起的MA和HW。理解纵向关联和机制 老年MA的睡眠和ADRD之间的关系将有助于及早发现和预防ADRD 服务不足的人群以及所有老年人。

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.