Project Abstract Aging is a known risk factor for the development of obstructive sleep apnea (OSA), although the underlying mechanisms are only recently being understood. OSA is associated with Alzheimer’s disease in epidemiological studies as well as having common genetic links. A number of mechanisms have been proposed including oxidative stress and amyloid and tau deposition which may contribute to the observed link. Recent prominent publications have hi-lighted the potential impact of sleep disruption on Alzheimer’s risk. We have clearly observed impairment in sleep-dependent memory consolidation even with mild OSA and have developed robust methods to assess these outcomes in a rigorous manner. Recent evidence suggests that OSA in older individuals may be a somewhat different disease than OSA in younger individuals, based on relatively unique underlying mechanisms. We have recently published and validated techniques allowing the assessment of the pathophysiology underlying OSA using minimally invasive methods making disease endotyping clinically accessible. We have also recently found subgroups of OSA patients who respond well to oxygen and can be predicted based on the underlying pathophysiology of OSA. We plan to study and further validate our model by assessing the impact of oxygen therapy in OSA patients who are at risk of developing Alzheimer’s disease. We have a robust panel of neurocognitive outcomes and have exciting preliminary data showing reversibility of some of the observed impairment in hippocampal memory. Moreover we are now working with expert imaging and neuropsychology collaborators who will help us define robust outcome metrics using MRI and PET scanning (e.g. volumetric analyses, amyloid, tau). Ultimately we hope that this application will lay the groundwork for a mechanistic comparative effectiveness trial whereby we can compare oxygen with standard therapy for select OSA patients in an effort to prevent the development of Alzheimer’s disease. Regardless of the results of the proposed work however we will gain major insights into the mechanisms and optimal care of elderly people with OSA.