Treatment of OSA on sleep-dependent memory and blood biomarkers in blacks

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PROJECT SUMMARY. Growing evidence suggests that obstructive sleep apnea (OSA) patients have cognitive impairments as well as increases in Alzheimer's disease (AD) biomarkers such as amyloid beta and tau. Positive airway pressure (PAP) therapy is an effective treatment for OSA but is often limited by suboptimal adherence. Anecdotal evidence show both short and long-term adequate OSA treatment improving attention, psychomotor speed, memory and executive function deficits associated with OSA. However, there is scarcity of data regarding the impact of OSA treatment among blacks on neurocognitive outcomes, despite having a disproportionate burden of OSA and AD, as well as a traditionally low treatment adherence. In this innovative hypothesis-driven study, we will address inadequate adherence to OSA treatment in blacks with “personalized multi-modal OSA treatment”, tailored to reduce health risks in minoritized communities by offering any combination of PAP, oral appliance therapy (OAT) and positional therapy, as well as address individual and system-level barriers through no-cost enrollment, personalized educational/instructional use, and real-time adherence monitoring that results in an effective reduction in AHI. Using a pre-and-post treatment design, we will examine the personalized multi-modal OSA treatment effect on within-subject changes on i) blood-based biomarkers of neurodegeneration (Aim 1), ii) sleep-dependent spatial navigational memory and functional magnetic resonance imaging (fMRI) (Aim 2), and iii) examine whether adequate sustained reductions in AHI at 12 months (effective AHI<15) are associated with sustained improvement in global cognition, standard declarative memory, attention and processing speed tests (Aim 3). Our central hypothesis is that the degree of effective AHI reduction by our personalized multi-modal OSA treatment will predict: 1. the longitudinal change in overnight plasma NfL; 2. the longitudinal change in brain circuit activity and spatial navigational memory improvement and 3. the degree of sustained improvements in sleep and cognitive performance at 12-months.We will leverage the success of our Sleep Disparity Workgroup in recruiting from minoritized communities, and the collaboration with affiliated sleep clinics and test our central hypothesis in a sample of 60 newly diagnosed moderate-to-severe OSA black subjects ages 45-75. Subjects will undergo full clinical evaluation, neuropsychological tests and clinical labs. Prior to and after 3-months of personalized multi-modal OSA treatment, all subjects will undergo a night of in-lab polysomnography with a pre-sleep and post-sleep blood draw and spatial navigational memory test in the MR scanner. A 12-month follow- up will also assess the effect of sustained improvements in sleep on changes in cognitive performance. Importantly, we will acquire and explore identifying socio-structural determinants of health (SDOH) factors that are associated with sustained treatment adherence to inform both clinical and public health practices targeting inadequate adherence and impact of OSA treatment on cognition in blacks.