Clinical Research Studies

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 such as diabetes and hypertension. 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. Reduced NREM SWS/SWA and inflammation are also associated with changes in cognition in late-life, and are more burdensome in blacks. Our central hypothesis is that black OSA participants will exhibit higher tau and greater neurodegeneration, as well as reduced NREM SWS/SWA and increased inflammation compared to their white counterparts, in the context of amyloid burden. Furthermore, we hypothesize structural/social determinants of health (SDOH; i.e., environmental, socio-structural, and behavioral factors) and vascular risk will mediate racial/ethnic 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 complaints of EDS (100 blacks & 50 whites). Subjects will be recruited primarily from the community, guided by principles of stakeholder-engaged research, and 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; one night of nocturnal polysomnography (NPSG) recording on visit 2; obtaining neuroimaging measures of vascular burden and amyloid on visit 3, and tau on visit 4, using 18F-florbetaben (FBB) and MK 6240 (with PI2620 as a backup) PET-MRI respectively, at baseline and at 2.5 years follow-up. More importantly, we will prioritize acquisition of SDOH data to elucidate disease mechanisms to aid future discovery of disease prevention targets.