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

使用健康差异研究框架来研究老年黑人/非裔美国人中阻塞性睡眠呼吸暂停与阿尔茨海默病较高风险之间的联系机制

• 批准号: 10662903
• 负责人: OMONIGHO A MICHAEL Bubu
• 金额: $ 174.36万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662903
• 关键词: Address; Affect; African American population; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Area; Behavioral; Black Populations; Black race; Blood Vessels; Body mass index; Brain; Cerebrospinal Fluid; Clinical; Cognition; Cognitive; Communities; Data; Diabetes Mellitus; Discrimination; Disease; Disease Outcome; Disease model; Education; Elderly; Eligibility Determination; Enrollment; Ethnic Origin; Excessive Daytime Sleepiness; Exhibits; Foundations; Future; Health Disparities Research; Heterogeneity; High Prevalence; Home; Hypertension; IL17 gene; Income; Inferior; Inflammation; Interleukin-6; Investigation; Knowledge; Laboratories; Lesion; Link; Magnetic Resonance Imaging; Measures; Mediating; Methods; Nerve Degeneration; Neuropsychological Tests; Newly Diagnosed; Not Hispanic or Latino; Obstructive Sleep Apnea; Older Population; Onset of illness; Participant; Pathologic; Pathology; Patient Care; Plasma; Polysomnography; Population Heterogeneity; Positron-Emission Tomography; Public Health; Public Health Practice; Race; Research; Resources; Risk; Risk Factors; Sampling; Science; Severities; Sleep; Slow-Wave Sleep; Socioeconomic Status; Stress; Surrogate Markers; TNF gene; Tauopathies; Temporal Lobe; Testing; Thick; United States National Institutes of Health; Visit; Work; actigraphy; allostatic load; cardiovascular risk factor; cohort; deprivation; disease disparity; entorhinal cortex; follow-up; health data; improved; in vivo; indexing; innovation; neuroimaging; new therapeutic target; non rapid eye movement; novel; perceived stress; racial difference; recruit; research clinical testing; sex; sleep quality; sleep regulation; social; social structure; stress management; structural health determinants; tau Proteins; tau-1; therapy design; tool; uptake; vascular risk factor; white matter; β-amyloid burden

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.

项目摘要/总结 黑人/非裔美国人（黑人）患阿尔茨海默病 (AD) 的风险是普通人的两倍 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。正在检查 其他危险因素和描述与老年黑人这种较高 AD 风险相关的病理机制是 优化患者护理模式所需的关键的第一步。阻塞性睡眠呼吸暂停 (OSA) 就是此类风险之一 因素。值得注意的是，黑人因白天过度嗜睡 (EDS) 而患 OSA 的负担较高，这与 具有纵向淀粉样蛋白-PET 摄取。 OSA 与非快速眼动 (NREM) 缓慢下降有关 波睡眠/活动 (SWS/SWA) 和炎症增加，这两者都会影响淀粉样蛋白和 tau 蛋白病理学。 NREM SWS/SWA 和炎症也与晚年认知变化相关，并且更重要 对黑人来说是负担。当前的提案将利用与老龄化相关的健康差异研究框架 (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) 检查健康的社会结构决定因素 (SDOH) 是否有助于解释 OSA 中的种族异质性 AD 结果。我们的 神经退行性疾病， 中心假设是黑人 OSA 受试者会表现出更高的 tau 蛋白和更大的 与白色 OSA 相比，NREM SWS/SWA 减少，炎症增加 受试者，在淀粉样蛋白负担的背景下。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 结果的种族异质性。我们 将在 300 名居住在社区的认知正常 (CN) 受试者的样本中检验我们的中心假设；年龄 55-85 匹配种族 (2:1)、年龄和性别，并通过教育、收入和 BMI 进行平衡。科目将包括 150 对照组（100 名黑人和 50 名白人），以及 150 名新诊断患有 EDS 的 OSA 受试者（100 名黑人和 50 名白人）。 该提案将从社区招募 125 名新黑人受试者 [80 名 OSA 和 45 名对照者] 并利用 175 人的现有数据和资源（75 名黑人 [20 名 OSA 和 55 名对照] 和 100 名白人 [50 名 OSA 和 50 名对照]） 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 以及两个附属机构正在进行的 NIH 支持的 R01 研究（R01AG056031 和 R01AG056531）。受试者将 接受 2 晚的 OSA 在家睡眠监测，然后进行 5 天的体动记录和睡眠日志。临床 第 1 次访视将包括全面的临床评估、神经心理学测试和临床实验室； 1晚夜间 第 2 次就诊时的多导睡眠图 (NPSG) 记录；血管负荷、淀粉样蛋白（18F- florbetaben) 和 tau (18F-PI2620) PET-MRI 分别在第 3 次和第 4 次就诊、基线和 2.5 年随访时进行。 重要的是，我们将优先获取 SDOH 数据来阐明疾病机制，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。