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Background: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-β (Aβ) burden, the hallmark of Alzheimer's disease, and cognitive decline. Objective: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. Methods: Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aβ burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. Results: Aβ burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aβ burden when controlling for sleep variables. Conclusions: Nocturnal hypoxemia was related to brain Aβ burden in this sample of OSA participants. Aβ burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aβ burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether it may be a therapeutic target for dementia prevention in OSA is yet to be determined. [ABSTRACT FROM AUTHOR]