Sleep Apnea Physiology and MRI-enlarged Perivascular Spaces in Community-Dwelling Adults.

INTRODUCTION:Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with cognitive impairment and cerebral small vessel disease (CSVD), including enlarged perivascular spaces (PVS). PVS are hypothesized to play a role in brain metabolite clearance. While some studies suggest an association between OSA and PVS enlargement, findings are inconsistent, and the specific physiological aspects of OSA driving these changes remain unclear. This study aimed to identify latent variables underlying sleep apnea physiology and relate them to PVS burden in a large community-based cohort. METHODS:We conducted a cross-sectional study of 614 participants from the Ontario Health Study who underwent home sleep apnea testing and brain MRI within 3 years. We computed 9 individual measures of sleep apnea physiology and performed factor analysis to identify latent variables. Linear regression models, adjusted for age, sex, and vascular risk factors, were used to assess associations between these latent variables and basal ganglia (BG) and non-basal ganglia (non-BG) PVS counts and volumes. RESULTS:Factor analysis yielded three latent variables accounting for 71.5% of the variance: an "apnea burden factor" (respiratory/desaturation event frequency), a "hypoxia factor" (chronic hypoxia), and a "duration factor" (event duration). In age- and sex-adjusted models, higher levels of the apnea burden factor were associated with higher BG-PVS counts (Estimate = +0.000040, SE = 0.000015, p = 0.007), while higher levels of the hypoxia factor were associated with higher non-BG PVS counts (Estimate = +0.068, SE = 0.0, p = 0.02). DISCUSSION:Our findings indicate that distinct physiological aspects of OSA are differentially associated with PVS burden. Greater respiratory event frequency is significantly associated with higher BG-PVS counts This highlights the importance of characterizing specific OSA endotypes to identify individuals at highest risk for PVS enlargement and to target relevant physiological pathways for intervention. Additional studies are needed to confirm causality and explore the impact of OSA treatment on PVS progression.