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/摘要 黑人/非裔美国人(黑人)患阿尔茨海默病(AD)的风险是 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。检视 与老年黑人AD风险较高相关的其他风险因素和病理机制是 这是优化患者护理范例所需的关键初始步骤。阻塞性睡眠呼吸暂停(OSA)就是这样的风险之一 因素。值得注意的是，黑人有更高的OSA负担和日间过度嗜睡(EDS)，这与 有纵向的淀粉样蛋白-PET摄取。阻塞性睡眠呼吸暂停与非快速眼动(NREM)减慢有关 波性睡眠/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变化有关，而且 黑人的负担太重了。目前的提案将利用与老龄化有关的健康差距研究框架 目的：(I)研究阻塞性睡眠呼吸暂停综合征对AD病理的种族内和种族间影响。(Ii)找出减少的NREM SWS/SWA和炎症增加是连接OSA和AD的潜在中间机制。(Iii) 研究社会结构健康决定因素(SDOH)是否有助于解释阻塞性睡眠呼吸暂停综合征的种族异质性。 广告效果。我们的 神经变性， 中心假设是黑人OSA受试者将表现出更高的tau和更大的 与白色OSA相比，NREM SWS/SWA减少，炎症增加 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)和血管风险将在OSA-AD结果中调节种族异质性。我们 将在300名社区居住的认知正常(CN)受试者中检验我们的中心假设；年龄 55-85人在种族(2：1)、年龄和性别上匹配，并在教育、收入和BMI方面取得平衡。科目将包括150个 对照组(100名黑人和50名白人)和150名新诊断的阻塞性睡眠呼吸暂停综合征患者(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名控制组]，并利用 175个(75个黑人[20个OSA和55个控制]和100个白人[50个OSA和50个控制]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类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R01研究(R01AG056031和R01AG056531)。研究对象将 对阻塞性睡眠呼吸暂停综合征患者进行2晚的居家睡眠监测，随后进行5天的动态监测和睡眠记录。临床 访问将包括完整的临床评估、神经心理测试和临床实验室；访问1晚；夜间访问 多导睡眠图(NPSG)记录2；血管负荷、淀粉样蛋白(18F-)的神经成像测量 氟倍他滨)和tau(18F-PI2620)PET-MRI分别在治疗3次和4次时、基线和2.5年随访时进行。 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.