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

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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.