Role of Sleep Apnea in Cognition and Alzheimer's Disease Biomarkers in WTC Responders

睡眠呼吸暂停在 WTC 应急人员认知和阿尔茨海默病生物标志物中的作用

基本信息

批准号：
10624882
负责人：
INDU A AYAPPA
金额：
$ 59.23万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624882
关键词：
Role Sleep Apnea Cognition Alzheimer

项目摘要

Project Summary Cognitive decline is the hallmark of Alzheimer’s disease (AD) and biomarkers to measure amyloid beta (Aβ) or tau burden are increasingly being used to identify early (pre-clinical) AD risk prior to emergence of cognitive impairment. Disturbances of sleep are common in AD, mild cognitive impairment and also in normal elderly with Aβ positive biomarkers. This suggests that: i) disturbed sleep contributes to AD-neurodegeneration (i.e. sleep disturbances such as from obstructive sleep apnea (OSA) are modifiable risk factors for AD); or, ii) sleep is particularly sensitive to Aβ and neurofibrillary tangle pathology (i.e. sleep disturbance is an early biomarker of AD), impacting quality of life. Our published data show that increased OSA severity in cognitively normal older subjects is associated with increased Aβ burden. Our preliminary data also show that OSA is associated with elevated cerebrospinal fluid (CSF) tau, a finding that may have a stronger link to cognitive decline. We have recently confirmed an increased prevalence (75%) of new-onset OSA in World Trade Center (WTC) dust- exposed subjects (i.e. responders) compared to the general population. The WTC responder cohort is aging and there is evidence of early cognitive impairment and high incidence of cognitive decline compared to age matched norms. This cohort is unique for its high prevalence of OSA, the availability of longitudinal data on presence and duration of OSA as well as information on other relevant risk factors for AD such as depression and post- traumatic stress disorder (PTSD), and provides a unique opportunity to evaluate the relationship between sleep disruption, biomarkers for AD risk and cognition. The purpose of the present proposal is to examine the impact of OSA severity and sleep related changes on AD plasma biomarkers, tau burden and cognition in WTC subjects using novel methodology and adjusting for potential confounders. Aim 1 will examine longitudinal changes in plasma tau and tau burden in 64 subjects with and without OSA to test the hypothesis that OSA severity is correlated with (i) changes in plasma tau and (ii) with greater longitudinal tau burden using PET-MR imaging using 18F-PI2620. Aim 2 will examine the relationship between OSA and cognition using a visual-spatial memory test (3D-maze) and the subtle cognitive impairment test (SCIT); both tests are sensitive to sleep disruption in subjects who are cognitively normal or minimally impaired by standard neuropsychological testing. We will test the hypothesis that OSA severity at baseline predicts longitudinal decline in spatial navigational memory and SCIT. Demonstration of a relationship between OSA, AD biomarkers and cognitive impairment suggests specific risk factors for AD might be assessed non-invasively (e.g. by maze/SCIT or by finding OSA or sleep specific biomarkers). These data will guide future interventional studies targeting sleep disruption (e.g. treatment of OSA, increase sleep duration) and outcomes (e.g. improvement in cognition) with the long-term goal of improving the quality of life and health outcomes in the WTC responder cohort.

项目概要认知能力下降是阿尔茨海默病 (AD) 的标志，也是测量淀粉样蛋白 (Aβ) 或淀粉样蛋白的生物标志物 tau 负担越来越多地用于在认知障碍出现之前识别早期（临床前）AD 风险睡眠障碍在AD、轻度认知障碍以及正常老年人中很常见。 Aβ 阳性生物标志物表明：i) 睡眠障碍会导致 AD 神经变性（即睡眠）。阻塞性睡眠呼吸暂停 (OSA) 等干扰是 AD 的可改变危险因素）；或者，ii) 睡眠是对 Aβ 和神经原纤维缠结病理特别敏感（即睡眠障碍是 Aβ 的早期生物标志物） AD），影响生活质量，我们公布的数据表明，认知正常的老年人的 OSA 严重程度增加。我们的初步数据还表明，OSA 与 Aβ 负担增加有关。脑脊液 (CSF) tau 蛋白升高，这一发现可能与认知能力下降有更强的联系。最近证实，世界贸易中心 (WTC) 灰尘中新发 OSA 的患病率有所增加 (75%) 与一般人群相比，暴露对象（即反应者）正在老龄化且严重。有证据表明，与年龄匹配的人相比，存在早期认知障碍和认知能力下降的高发生率该队列的独特之处在于 OSA 患病率高、存在和存在的纵向数据的可用性。 OSA 的持续时间以及 AD 的其他相关危险因素（例如抑郁症和术后睡眠障碍）的信息创伤性应激障碍 (PTSD)，并提供了评估睡眠与创伤性应激障碍 (PTSD) 之间关系的独特机会干扰、AD 风险和认知的生物标志物本提案的目的是检查其影响。 WTC 受试者中 OSA 严重程度和睡眠相关变化对 AD 血浆生物标志物、tau 蛋白负荷和认知的影响使用新颖的方法并调整潜在的混杂因素，目标 1 将检查纵向变化。对 64 名患有和不患有 OSA 的受试者进行血浆 tau 和 tau 负荷，以检验 OSA 严重程度与使用 PET-MR 成像与 (i) 血浆 tau 变化和 (ii) 更大的纵向 tau 负荷相关使用 18F-PI2620 目标 2 将使用视觉空间记忆检查 OSA 和认知之间的关系。测试（3D 迷宫）和微妙认知障碍测试（SCIT）；这两种测试都对睡眠中断敏感。我们将测试通过标准神经心理学测试认知正常或轻度受损的受试者。基线 OSA 严重程度预示空间导航记忆纵向下降的假设 SCIT。OSA、AD 生物标志物和认知障碍之间关系的证明表明了特定的关系。 AD 的危险因素可以进行非侵入性评估（例如通过迷宫/SCIT 或通过寻找 OSA 或睡眠特异性）这些数据将指导未来针对睡眠障碍的干预研究（例如治疗 OSA（增加睡眠时间）和结果（例如认知能力的改善），长期目标是改善世贸中心响应者队列的生活质量和健康结果。