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.

项目摘要 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“睡眠是大脑的，由大脑控制，为了大脑”这句格言的兴趣。 大脑相对于睡眠良好的成年人，那些表现出睡眠不足（SD）的人，定义为睡眠不好，睡眠不足 呼吸暂停和/或昼夜节律失调，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在AD病程的早期观察到，因此它构成了AD治疗的主要目标。 预防尽管在描述睡眠的机制和功能方面取得了成功， 仍在阐明黑人睡眠差异的因素，其特点是AD风险更高 负担黑人也承担着更大的睡眠负担，这一点可以从主要睡眠缺陷的发生率较高得到证明。 这些指标与血管风险增加、炎症、脑损伤和认知障碍有关。 多学科团队将利用创新的动态和地理空间建模， 一个框架来描述SD的心理社会和环境决定因素及其对 老年黑人的大脑健康我们将利用纽约大学睡眠差异工作组的成功， 包括具有衰老研究、平移睡眠和昼夜节律科学、脑 健康、健康差距以及地理空间和多层次动态建模。我们将利用社会 我们的社区指导委员会的资本和资产，从传统的504名黑人（60-75岁） 和非传统场所来获取研究终点。我们将调查以下目标：1） 确定社会心理（社会/情感支持、情绪、歧视、态度）和环境 （住户[密度、噪音、空气质量、光照和温度]、社会经济地位、社会资本、 社区[建筑环境]）与SD相关的因素; 2）评估SD对 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 （注意力、语言、记忆和执行功能，使用临床前阿尔茨海默氏症认知综合征） 和Trail Making Test）。血管风险（肥胖、血压、血脂和葡萄糖/HbA 1C）和 将对炎症（IL-6、IL-10和TNF-α）进行加权; 3）表征风险增加的黑人 SD使用贝叶斯机器学习建模和预测，通过基于代理的建模， 心理社会和环境变化的融合将导致减少SD负担和相关的 随着时间的推移（5，10和20岁），老年黑人的大脑健康状况。调查小组将使用小说 基于家庭的数字记录仪，创新的大脑健康生物标志物，地理空间分析和动态 系统建模，以描述SD的机制，并描绘他们的潜在作用，解释 观察到老年黑人大脑健康标志物的差异。