Slow wave sleep (SWS) and the effect of African ancestry on amyloid burden, a longitudinal study

7.项目总结/摘要： 与白人相比，非洲裔美国人（AA）的阿尔茨海默病（AD）患病率增加， 这在传统上与血管疾病的存在有关。然而，最近的一个社区- 一项基于非痴呆老年人的研究，以及我们的初步数据，表明AA具有更高的淀粉样蛋白， 调整血管风险因素后的负担，这表明存在额外的遗传或 不同种族的AD风险的生理差异。本研究的目的是测试慢波睡眠不佳是否 (SWS)就是这些因素之一。睡眠障碍在AA和非西班牙裔白人之间存在差异。AA需要更长时间 入睡，睡眠时间较短，睡眠效率较低，更典型的是SWS持续时间较短 与白人相比。与此相关的是，淀粉样蛋白阳性的健康老年人，以及那些有轻度认知障碍的人， 轻度认知功能障碍（MCI）和AD患者，经历更多的睡眠碎片和更多的SWS和REM睡眠减少 比健康的人更长寿。这表明：i）睡眠障碍有助于AD- 神经变性（或睡眠对淀粉样蛋白沉积特别敏感）;以及，ii）种族相关的睡眠 这些差异可能导致AA中淀粉样蛋白负荷的增加。这项研究有两个目标：第一， 证实黑人在体内与淀粉样蛋白-PET摄取的纵向增加相关， 认知能力下降;第二，证明基线时SWS较差与 控制心血管疾病的发病率是睡眠障碍和痴呆症之间的共享， 混淆这些协会。在与社区利益相关者协商后，我们将招募150名 正常AA老年人（年龄55 - 75岁）和60名白人，按年龄、性别、BMI、教育和其他社会因素平衡。 人口统计学变量和来自相同的布鲁克林社区。第一次访视将包括完整的临床 评估、神经心理学测试和临床实验室。参与者随后将接受OSA的家庭监测 两个晚上，接着是5天的腕动记录。睡眠呼吸正常的受试者将被邀请进行 2个晚上的夜间多导睡眠图（NPSG），然后进行第二次最终访视，其中淀粉样蛋白负荷和 将通过11C-PiB PET-MR分析脑血管发病率。将邀请所有受试者重复两次访视 30个月后。这项研究有可能确定认知障碍中淀粉样蛋白负荷的临床预测因子。 这将是在黑人社区预防痴呆症的重要一步 以及减少卫生不平等。

7. PROJECT SUMMARY/ABSTRACT: African-Americans (AAs) have an increased prevalence of Alzheimer's disease (AD) compared to whites, which traditionally has been associated to the presence of vascular disease. However, a recent community- based study of non-demented elderly, as well as our preliminary data, suggest that AAs have higher amyloid burden after adjusting for vascular risk factors, which points to the presence of additional genetic or physiological differences on AD-risk by race. The purpose of this study is to test whether poor slow wave sleep (SWS) is one of these factors. Sleep disturbances vary between AAs and non-Hispanic whites. AAs take longer to fall asleep, have shorter sleep duration, lower sleep efficiency and, more characteristically, less SWS duration when compared to whites. Relatedly, amyloid positive healthy elderly, as well as those with mild cognitive impairment (MCI) and AD, experience more sleep fragmentation and more decreased SWS and REM sleep duration than their healthy counterparts. This suggests: i) that disturbed sleep contributes to AD- neurodegeneration (or that sleep is particularly sensitive to amyloid deposition); and, ii) that race-related sleep differences might contribute to the reported increases in amyloid burden in AAs. The study has two goals: first, to confirm that black race is associated in vivo with longitudinal increases in amyloid-PET uptake and cognitive decline; second, to demostrate that poor SWS at baseline is associated with these increases after controling for the cardiovascular morbidity that is shared between sleep disturbances and dementia and might confound these associations. In consultation with community stakeholders, we will recruit 150 cognitively normal AA elderly (ages 55-75 years) and 60 whites balanced by age, sex, BMI, education and other socio- demographic variables and from the same Brooklyn neighborhoods. Visit one will include a full clinical evaluation, neuropsychological tests and clinical labs. Participants will later undergo home monitoring for OSA for two nights followed by 5 days of actigraphy. Subjects with normal sleep breathing will be invited to perform 2 nights of nocturnal polysomnography (NPSG) followed by a second final visit in which amyloid load and cerebrovascular morbidity will be analyzed by 11C-PiB PET-MR. All subjects will be invited to repeat both visits after 30 months. This study has the potential to identify clinical predictors of amyloid burden in cognitively normal AA elderly and would be an important step towards the prevention of dementia in the black community as well as the reduction of health inequities.