Obstructive Sleep Apnea and Cerebral Microbleeds in Middle-Aged and Older Adults

Importance The association of obstructive sleep apnea (OSA) with risk of incident cerebral microbleeds (CMBs) is unknown. Objective To investigate the association between OSA severity and risk of incident CMBs in the late middle-aged general population. Design, Setting, and Participants This cohort study included eligible participants who had in-home overnight polysomnography data and brain magnetic resonance imaging done at baseline (2011-2014) and 4-year follow-ups (first follow-up, 2015-2018, and second follow-up, 2019-2022) from an ongoing longitudinal cohort study of a Korean community of adults. Data were analyzed from March 2024 through January 2025. Exposures OSA severity was categorized by apnea-hypopnea index levels as no OSA (0-4.9 events/h), mild OSA (5.0-14.9 events/h), and moderate to severe OSA (≥15.0 events/h). Main Outcomes and Measures CMBs were defined as well-defined focal areas (<10 mm in diameter) of very low signal intensity on gradient echo T2*-weighted images. Modified Poisson regression (robust error variance) was used to estimate relative risk (RR), with 95% CIs, of incident CMBs by OSA group; adjustment was done for age, sex, education level, body mass index, physical activity level, smoking and drinking status, total and low-density lipoprotein cholesterol level, hypertension, diabetes, age-related white matter changes, change in apnea-hypopnea index level, change in body mass index, and mean arterial pressure of the corresponding follow-up. Results Of 1441 study participants (mean [SD] age, 57.75 [5.53] years; 759 female [52.67%]), 436 participants (30.25%) and 193 participants (13.39%) had mild and moderate to severe OSA at baseline, respectively; 812 participants had no OSA. The cumulative incidence rate of CMBs in non-OSA, mild OSA, and moderate to severe OSA groups was 15 participants (1.85%), 7 participants (1.61%), and 9 participants (4.66%), respectively, at 4 years and 27 participants (3.33%), 14 participants (3.21%), and 14 participants (7.25%), respectively, at 8 years. In multivariable modified Poisson models, participants with moderate to severe OSA compared with the non-OSA group had an increased risk of developing CMBs at 8 years (RR, 2.14; 95% CI, 1.08-4.23; P = .02). These results were unaffected by the presence or absence of APOE-ε4 carrier status. No significantly increased risks were observed at 4 years or in the mild OSA group at any time. Conclusions and Relevance In this study, moderate to severe OSA was independently associated with an increased risk of incident CMBs over an 8-year follow-up. These results add to the evidence for the importance of sleep apnea to brain health.