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

老年墨西哥裔美国人和非西班牙裔白人的睡眠质量及其与阿尔茨海默病和相关疾病的机制联系

• 批准号: 10018634
• 负责人: Sid E O'Bryant
• 金额: $ 77.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018634
• 关键词: Accounting; Address; Adult; Affect; Age; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Ancillary Study; Animal Model; Atrophic; Biological Markers; Blood; Blood Vessels; Brain; Characteristics; Clinical; Cognition; Cognitive; Cognitive aging; Communities; Data; Dementia; Deposition; Diabetes Mellitus; Disease; Early Diagnosis; Elderly; Ethnic group; Face; Functional disorder; Health; Hispanics; Hypertension; Impaired cognition; Inflammation; Inflammatory; Investigation; Knowledge; Latino; Lesion; Light; Link; Magnetic Resonance Imaging; Measures; Mediating; Metabolic; Mexican Americans; Nerve Degeneration; Neurosciences; Not Hispanic or Latino; Outcome; Participant; Pathway interactions; Patients; Peripheral; Plasma; Population Heterogeneity; Positioning Attribute; Positron-Emission Tomography; Prevention; Prospective Studies; Public Health; Quality of life; Rest; Risk; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Sleeplessness; Underserved Population; Vascular Diseases; aging brain; caucasian American; cognitive function; cost; cost efficient; ethnic diversity; experience; health disparity; hippocampal atrophy; innovation; mild cognitive impairment; multidisciplinary; neurofilament; nocturnal Hypoxemia; phenotypic biomarker; polypeptide; racial diversity; sleep quality; tau Proteins; vascular inflammation; white matter

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.

项目概要/摘要 临床神经科学最近最令人兴奋的进展之一是建立了一种连接 睡眠与阿尔茨海默病和相关痴呆症 (ADRD) 之间的关系。经常患有 ADRD 的患者 睡眠质量差/紊乱，并且越来越多的证据（包括来自我们团队的证据）表明，睡眠质量差/睡眠障碍 睡眠质量会增加患 ADRD 的风险。这种双向关联对于 预防和治疗，但仍然存在许多问题。墨西哥裔美国人 (MA) 代表最快 美国和马萨诸塞州不断增长的族裔群体面临着许多健康差距，包括更大的健康差异 与非西班牙裔白人 (NHW) 相比的代谢/血管风险。最近的证据虽然有争议， 表明西班牙裔人存在更大的主观睡眠问题，但老年西班牙裔人缺乏这些数据， 尤其是 MA，人们对客观测量的睡眠知之甚少。我们的成本效益和创新研究 将解决其中许多差距。该提案的总体目标是确定之间的关联 睡眠质量（客观和主观测量）和认知障碍，包括 MA 和 ADRD NHW，并阐明连接这些条件的目标途径。我们将利用正在进行的健康与 拉丁裔老年人大脑老化 (HABLE) 研究以经济有效的方式调查客观测量的睡眠 500 名社区居民 MA 和 500 名 NHW 的认知障碍程度（约 40%） 患有轻度认知障碍/ADRD）。 HABLE 研究具有深入的表型分析和生物标志物 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，经济有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 辅助研究的一部分来实现： 1) 描述老年 NHW 和 MA 在认知方面的客观和主观睡眠质量 谱，2) 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) 确定睡眠质量与关键机制途径（包括血管和神经系统）之间的关联 炎症和 4) 研究睡眠质量与淀粉样蛋白生物标志物 (PET 扫描和血浆 Aβ40 和 Aβ42）以及其他神经变性指标（血浆 tau、NFL 和 海马萎缩）。我们拥有前所未有的机会，与经验丰富且 多学科团队，首次对几个关键途径进行全面调查 MA 和 NHW 可能将睡眠与 ADRD 联系起来。了解纵向关联和机制 老年 MA 中睡眠与 ADRD 之间的关系将有助于早期发现和预防 ADRD 服务不足的人群以及所有老年人。