Using a Health Disparity Research Framework to examine mechanisms linking Obstructive Sleep Apnea with higher Alzheimer’s disease risk in older Blacks/African-Americans

项目摘要/总结 黑人/非洲裔美国人（黑人）患阿尔茨海默病（AD）的风险是其他人的两倍。 非西班牙裔白人（白人），部分原因是血管危险因素的患病率较高。检查 其他风险因素和描绘与老年黑人AD风险较高相关的病理机制， 这是优化患者护理模式所需的关键初始步骤。阻塞性睡眠呼吸暂停（OSA）就是这样一种风险 因子值得注意的是，黑人有更高的OSA负担，伴有过度的日间嗜睡（EDS），这与 有纵向淀粉样蛋白PET摄取。OSA与非快速眼动（NREM）减慢有关。 波睡眠/活动（SWS/SWA）和炎症增加，这两者都影响淀粉样蛋白和tau病理。 NREM SWS/SWA和炎症也与晚年认知的变化有关，并且更重要的是， 在黑人中是累赘。目前的提案将利用与老龄化有关的健康差异研究框架 目的：（i）研究OSA对AD病理学的种族内和种族间影响。(ii)识别NREM减少 SWS/SWA和炎症增加是连接OSA和AD的潜在中间机制。（三） 研究健康的社会结构决定因素（SDOH）是否有助于解释OSA的种族异质性- AD结果。我们 神经变性， 中心假设是，黑人OSA受试者将表现出更高的tau蛋白和更大的 与白色OSA相比， 受试者，在淀粉样蛋白负荷的背景下。此外，我们假设SDOH（即，环境，社会， 结构和行为因素）和血管风险将介导OSA-AD结局的种族异质性。我们 将在300名社区居住的认知正常（CN）受试者的样本中检验我们的中心假设;年龄 55-85在种族（2：1），年龄和性别上匹配，并通过教育，收入和BMI平衡。受试者将包括150名 对照组（100名黑人和50名白人）和150名新诊断的患有EDS的OSA受试者（100名黑人和50名白人）。 这项提案将从社区招募125名新的黑人受试者[80名OSA和45名对照]， 175例（75例黑人[20例OSA和55例对照]和100例白人[50例OSA和50例对照]）的现有数据和资源 来自纽约大学阿尔茨海默病研究中心的具有相似资格标准的社区居住CN受试者 两个附属的正在进行的NIH支持R 01研究（R 01 AG 056031和R 01 AG 056531）。受试者将 进行2晚的OSA家庭睡眠监测，然后进行5天的活动记录和睡眠日志。临床 访视将包括访视1时的全面临床评价、神经心理学测试和临床实验室检查; 1晚夜间 访视2时记录多导睡眠图（NPSG）;血管负荷、淀粉样蛋白（18 F- 在基线和2.5年随访时，分别在访视3和访视4时进行tau（18F-PI 2620）PET-MRI检查。 重要的是，我们将优先获取SDOH数据，以阐明疾病机制，以帮助未来的发现 新的AD预防目标，例如针对OSA中的压力管理，炎症和睡眠质量。

PROJECT ABSTRACT/SUMMARY Blacks/African-Americans (blacks) have two times the risk of developing Alzheimer’s disease (AD) compared to non-Hispanic whites (whites), in part attributable to the higher prevalence of vascular risk factors. Examining other risk factors and delineating pathological mechanisms associated with this higher AD-risk in older blacks is a critical initial step needed to optimize patient care paradigms. Obstructive sleep apnea (OSA) is one such risk factor. Notably, blacks have a higher burden of OSA with excessive daytime sleepiness (EDS), which is associated with longitudinal amyloid-PET uptake. OSA is associated with decreased non rapid eye movement (NREM) slow wave sleep/activity (SWS/SWA) and increased inflammation, both of which affect amyloid and tau pathology. NREM SWS/SWA and inflammation are also associated with changes in cognition in late-life, and are more burdensome in blacks. The current proposal will utilize a health disparities research framework related to aging to: (i) investigate within and between race effects of OSA on AD pathology. (ii) Identify decreased NREM SWS/SWA and increased inflammation as potential intermediate mechanisms linking OSA and AD. (iii) Examine whether socio-structural determinants of health (SDOH) can help explain racial heterogeneity in OSA- AD outcomes. Our neurodegeneration, central hypothesis is that black OSA subjects will exhibit higher tau and greater as well as reduced NREM SWS/SWA and increased inflammation compared to white OSA subjects, in the context of amyloid burden. Furthermore, we hypothesize SDOH (i.e., environmental, socio- structural, and behavioral factors) and vascular risk will mediate racial heterogeneity in OSA-AD outcomes. We will test our central hypothesis in a sample of 300 community-dwelling cognitively normal (CN) subjects; ages 55-85 matched on race (2:1), age and sex, and balanced by education, income and BMI. Subjects will include 150 controls (100 blacks & 50 whites), and 150 newly diagnosed OSA subjects with EDS (100 blacks & 50 whites). This proposal will recruit from the community, 125 new black subjects [80 OSA and 45 controls] and leverage existing data and resources in 175 (75 blacks [20 OSA and 55 controls] & 100 whites [50 OSA and 50 controls]) community-dwelling CN subjects with similar eligibility criteria, from NYU Alzheimer’s Disease Research Center and two-affiliated ongoing NIH supported R01 studies (R01AG056031 and R01AG056531). Subjects will undergo 2 nights of at-home sleep monitoring for OSA, followed by 5 days of actigraphy and sleep logs. Clinical visits will include full clinical evaluation, neuropsychological tests and clinical labs on visit 1; 1 night of nocturnal polysomnography (NPSG) recording on visit 2; neuroimaging measures of vascular burden, amyloid (18F- florbetaben) and tau (18F-PI2620) PET-MRI on visits 3 and 4 respectively, at baseline and at 2.5 years follow-up. Importantly, we will prioritize acquisition of SDOH data to elucidate disease mechanisms to aid future discovery of novel AD prevention targets e.g. targeting stress management, inflammation and sleep quality in OSA.