Using a Health Disparity Research Framework to examine mechanisms linking Obstructive Sleep Apnea with higher Alzheimer’s disease risk in older Blacks/African-Americans

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PROJECT ABSTRACT/SUMMARY Blacks/African-Americans (blacks) have two times the risk of developing Alzheimer’s disease (AD) compared to non-Hispanic whites (whites), in part attributable to the higher prevalence of vascular risk factors. Examining other risk factors and delineating pathological mechanisms associated with this higher AD-risk in older blacks is a critical initial step needed to optimize patient care paradigms. Obstructive sleep apnea (OSA) is one such risk factor. Notably, blacks have a higher burden of OSA with excessive daytime sleepiness (EDS), which is associated with longitudinal amyloid-PET uptake. OSA is associated with decreased non rapid eye movement (NREM) slow wave sleep/activity (SWS/SWA) and increased inflammation, both of which affect amyloid and tau pathology. NREM SWS/SWA and inflammation are also associated with changes in cognition in late-life, and are more burdensome in blacks. The current proposal will utilize a health disparities research framework related to aging to: (i) investigate within and between race effects of OSA on AD pathology. (ii) Identify decreased NREM SWS/SWA and increased inflammation as potential intermediate mechanisms linking OSA and AD. (iii) Examine whether socio-structural determinants of health (SDOH) can help explain racial heterogeneity in OSA- AD outcomes. Our neurodegeneration, central hypothesis is that black OSA subjects will exhibit higher tau and greater as well as reduced NREM SWS/SWA and increased inflammation compared to white OSA subjects, in the context of amyloid burden. Furthermore, we hypothesize SDOH (i.e., environmental, socio- structural, and behavioral factors) and vascular risk will mediate racial heterogeneity in OSA-AD outcomes. We will test our central hypothesis in a sample of 300 community-dwelling cognitively normal (CN) subjects; ages 55-85 matched on race (2:1), age and sex, and balanced by education, income and BMI. Subjects will include 150 controls (100 blacks & 50 whites), and 150 newly diagnosed OSA subjects with EDS (100 blacks & 50 whites). This proposal will recruit from the community, 125 new black subjects [80 OSA and 45 controls] and leverage existing data and resources in 175 (75 blacks [20 OSA and 55 controls] & 100 whites [50 OSA and 50 controls]) community-dwelling CN subjects with similar eligibility criteria, from NYU Alzheimer’s Disease Research Center and two-affiliated ongoing NIH supported R01 studies (R01AG056031 and R01AG056531). Subjects will undergo 2 nights of at-home sleep monitoring for OSA, followed by 5 days of actigraphy and sleep logs. Clinical visits will include full clinical evaluation, neuropsychological tests and clinical labs on visit 1; 1 night of nocturnal polysomnography (NPSG) recording on visit 2; neuroimaging measures of vascular burden, amyloid (18F- florbetaben) and tau (18F-PI2620) PET-MRI on visits 3 and 4 respectively, at baseline and at 2.5 years follow-up. Importantly, we will prioritize acquisition of SDOH data to elucidate disease mechanisms to aid future discovery of novel AD prevention targets e.g. targeting stress management, inflammation and sleep quality in OSA.