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

초록

<bold>Importance</bold> The association of obstructive sleep apnea (OSA) with risk of incident cerebral microbleeds (CMBs) is unknown. <bold>Objective</bold> To investigate the association between OSA severity and risk of incident CMBs in the late middle-aged general population. <bold>Design, Setting, and Participants</bold> 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. <bold>Exposures</bold> 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). <bold>Main Outcomes and Measures</bold> 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. <bold>Results</bold> 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-epsilon 4 carrier status. No significantly increased risks were observed at 4 years or in the mild OSA group at any time. <bold>Conclusions and Relevance</bold> 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.

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