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/摘要 黑人/非裔美国人（黑人）的风险是患阿尔茨海默氏病（AD）的两倍 非西班牙裔白人（白人），部分归因于较高的血管危险因素。检查 其他危险因素和与较高黑人的广告风险相关的描述的病理机制是 优化患者护理范例所需的关键初步步骤。阻塞性睡眠呼吸暂停（OSA）就是一种风险 因素。值得注意的是，黑人的OSA燃烧较高，白天嗜睡过多（EDS），这是相关的 纵向淀粉样蛋白叶子的吸收。 OSA与慢速运动（NREM）慢相关 波浪睡眠/活动（SWS/SWA）和感染增加，这两者都会影响淀粉样蛋白和TAU病理学。 NREM SWS/SWA和炎症也与后期认知的变化有关，并且更多 黑色的燃烧。当前的建议将利用与衰老有关的健康差异研究框架 至：（i）研究OSA对AD病理的种族影响之间的研究。 （ii）确定NREM减少 SWS/SWA并增加了感染，作为连接OSA和AD的潜在中间机制。 （iii） 检查健康的社会结构决定者（SDOH）是否可以帮助解释OSA-的种族异质性 广告结果。我们的 神经变性， 中心假设是黑色OSA受试者将暴露于更高的tau和更大的 与白色OSA相比 受试者，在淀粉样蛋白的背景下。此外，我们假设SDOH（即环境，社会 - 结构性和行为因素）和血管风险将在OSA-AD结果中中值拉面异质性。我们 将在300个社区居住在认知上正常（CN）受试者的样本中检验我们的中心假设；年龄 55-85在比赛（2：1），年龄和性别匹配，并通过教育，收入和BMI平衡。主题将包括150 对照（100个黑人和50个白人）和150名具有EDS（100个黑人和50名白人）的新诊断的OSA受试者。 该提案将从社区招募，125名新黑人主题[80 OSA和45个控件]和杠杆作用 现有的数据和资源175（75个黑人[20 OSA和55个控件]和100个白人[50 OSA和50个对照]） 来自纽约大学阿尔茨海默氏病研究中心的社区居住CN受试者具有相似的资格标准 以及两种相关的NIH支持R01研究（R01AG056031和R01AG056531）。受试者会 对OSA进行了2晚的家庭睡眠监测，然后进行5天的行为和睡眠原木。临床 访问将包括完整的临床评估，神经心理学测试和访问1的临床实验室；夜间1晚 访问2录制的多个选志（NPSG）录制；淀粉样蛋白的神经影像学措施（18f- Florbetaben）和Tau（18F-PI2620）PET-MRI分别访问3和4，在基线和2。5年的随访中。 重要的是，我们将优先考虑获得SDOH数据以阐明疾病机制以帮助未来的发现 新型AD预防目标，例如针对OSA的压力管理，感染和睡眠质量。