Mechanisms of sleep deficiency and effects on brain injury and neurocognitive functions among older blacks

老年黑人睡眠不足的机制及其对脑损伤和神经认知功能的影响

• 批准号: 10469160
• 负责人: Girardin Jean-Louis
• 金额: $ 64.69万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469160
• 关键词: Mechanisms; sleep; deficiency; effects; brain

Project Summary Translational studies showing a mechanistic interplay between Alzheimer’s disease (AD) pathogenesis and sleep/circadian disruption has renewed interest in the maxim ‘sleep is of the brain, by the brain, and for the brain’. Relative to adults sleeping well, those exhibiting sleep deficiency (SD), defined as poor sleep, sleep apnea, and/or circadian misalignment, have greater AD risk (OR=1.55), cognitive decline (OR=1.68), or preclinical AD (OR=3.78). Since SD is observed early in the course of AD, it constitutes a prime target for prevention. Notwithstanding successes in delineating the mechanisms and functions of sleep, a critical gap remains in elucidating factors undergirding sleep disparities among blacks, marked by a greater AD risk burden. Blacks also shoulder a greater sleep burden as evidenced by a higher prevalence of the main SD indices, which are linked to increased vascular risks, inflammation, brain injury, and cognitive impairment. The multi-disciplinary team will utilize innovative dynamic and geospatial modeling in a multi-level framework to delineate the psychosocial and environmental determinants of SD and its putative effects on the brain health of older blacks. We will leverage the success of the NYU Sleep Disparity Workgroup, comprising investigators with expertise in aging research, translational sleep and circadian sciences, brain health, health disparities, and geospatial and multi-level dynamic modeling. We will leverage the social capital and assets of our Community Steering Committee to enroll 504 blacks (60-75 years) from traditional and non-traditional venues to capture study endpoints. We will investigative the following aims: 1) To ascertain the psychosocial (social/emotional support, mood, discrimination, attitudes) and environmental (household [density, noise, air quality, light, and temperature], socioeconomic position, social capital, neighborhood [built environment]) factors that are associated with SD; 2) To assess effects of SD on markers of brain injury (Hcy, NFL, GFAP, Tau & Amyloid-β peptides) and on neurocognitive functions (attention, language, memory, and executive function using the Preclinical Alzheimer Cognitive Composite and Trail Making Test). The contributions of vascular risk (obesity, BP, lipid, and glucose/HbA1C) and inflammation (IL-6, IL-10, and TNF-α) will be weighted; 3) To characterize blacks who are at increased risk of SD using Bayesian machine-learning modeling and forecast through Agent-Based modeling which amalgamation of psychosocial and environmental changes will lead to a reduced SD burden and related brain health profile among older blacks over time (5, 10, & 20 yrs.). The investigative team will use novel home-based digital recorders, innovative brain health biomarkers, geospatial analytics and dynamic systems modeling to describe the mechanisms of SD and delineate their potential role in explaining observed disparities in markers of brain health of older blacks.

项目概要 转化研究显示阿尔茨海默病（AD）发病机制与 睡眠/昼夜节律紊乱重新引起了人们对这句格言的兴趣：“睡眠属于大脑，由大脑决定，并且为了睡眠”。 相对于睡眠良好的成年人，那些表现出睡眠不足（SD）（定义为睡眠不佳）的人。 呼吸暂停和/或昼夜节律失调具有更大的 AD 风险 (OR=1.55)、认知能力下降 (OR=1.68)，或 临床前 AD (OR=3.78) 由于 SD 是在 AD 病程早期观察到的，因此它构成了 AD 的主要目标。 尽管在描述睡眠的机制和功能方面取得了成功，但仍存在重大差距。 仍在阐明导致黑人睡眠差异的因素，其特点是 AD 风险更大 黑人还承担着更大的睡眠负担，主要睡眠障碍的患病率较高就证明了这一点。 这与血管风险增加、炎症、脑损伤和认知障碍有关。 多学科团队将在多层次中利用创新的动态和地理空间建​​模 框架来描述可持续发展的社会心理和环境决定因素及其对人的假定影响 我们将利用纽约大学睡眠差异工作组的成功， 由在衰老研究、转化睡眠和昼夜节律科学、脑科学等方面具有专业知识的研究人员组成 我们将利用社会健康、健康差异以及地理空间和多层次动态建模。 我们的社区指导委员会的资金和资产将招收 504 名传统黑人（60-75 岁） 我们将研究以下目标：1） 确定社会心理（社会/情感支持、情绪、歧视、态度）和环境 （家庭[密度、噪音、空气质量、光线和温度]、社会资本、 与可持续发展相关的邻里[建筑环境]）因素；2) 评估可持续发展对环境的影响； 脑损伤标志物（Hcy、NFL、GFAP、Tau 和淀粉样蛋白-β 肽）和神经认知功能 （使用临床前阿尔茨海默氏症认知复合物的注意力、语言、记忆和执行功能 和追踪测试）。血管风险（肥胖、血压、血脂和葡萄糖/HbA1C）的影响。 炎症（IL-6、IL-10 和 TNF-α）将被加权；3) 表征风险较高的黑人； 使用贝叶斯机器学习建模进行 SD 的分析，并通过基于代理的建模进行预测 心理社会和环境变化的结合将导致可持续发展负担和相关的减轻 调查小组将使用新颖的方法来了解老年黑人随时间推移（5、10 和 20 岁）的大脑健康状况。 家用数字记录器、创新的大脑健康生物标记、地理空间分析和动态 系统建模来描述 SD 的机制并描绘其在解释中的潜在作用 观察到老年黑人大脑健康指标的差异。