Sleep apnea treatment and risk for cognitive decline and Alzheimers disease

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ABSTRACT The prevalence of Alzheimer’s disease and related dementias (ADRD) is expected to increase four-fold by 2050. Consequently, there are efforts to identify “actionable” risk factors, that if identified and addressed early, have the potential to prevent cognitive decline and onset of ADRD. Obstructive sleep apnea (OSA) is associated with risk of cognitive decline and ADRD, particularly among older adults. As effective treatments are available for the condition (e.g., Continuous Positive Airway Pressure [CPAP]) that are demonstrated to be highly efficacious when used adherently, OSA may be an ideal target for ADRD risk reduction. In this study, we propose to characterize associations between OSA treatment (specifically CPAP) and cognitive decline and ADRD over up to 14 years of follow-up (2010-2024) in two nationally representative NIA-funded cohorts of U.S. older adults: the Health and Retirement Study (HRS), and National Health and Aging Trends Study (NHATS). We also intend to determine whether the effects of OSA treatment on cognition differ in those at higher risk for ADRD (e.g., minority race/ethnicity, advanced age, cardiovascular risk factors/disease, etc.) in order to identify populations among whom treatment is most likely to yield effects and ways OSA treatments could be optimized in groups not benefiting. Both HRS and NHATS include nationally representative samples, have repeated performance- based cognitive measures to characterize cognitive performance trajectories and ADRD, and linkages to Medicare claims for ascertainment of OSA diagnosis and treatment. The study will use innovative methods to harmonize datasets and will address three specific aims. Aim 1 will be to determine the association of OSA with cognitive trajectories and incident ADRD from 2010-2024, and examine whether OSA interacts with other ADRD risk factors with regard to cognitive decline and ADRD risk. Aim 2 will be to determine, among individuals with OSA, whether CPAP is associated with better cognitive outcomes from 2010-2024. Specifically, we will examine whether a) receipt of CPAP (compared to no treatment) is associated with slower cognitive decline and lower risk for ADRD, b) among those treated whether initiation of CPAP is associated with a slowing of cognitive decline and lower risk for ADRD before and after initiation, and c) whether these associations vary across levels of CPAP adherence. Finally, Aim 3 will examine whether associations found in Aim 2 will differ across known ADRD risk factors. If we find that addressing OSA is particularly effective in slowing cognitive decline/preventing ADRD, especially in high-risk groups, then our study’s results will help us understand the means by which OSA can be treated in the population and contribute to development of programs to treat OSA in these populations at greatest risk. Further, it will inform efforts to curb the burden of ADRD in the U.S. and contribute substantially to dementia prevention efforts.