The first prospective, longitudinal study of OSA and cerebral microbleeds (CMBs) found that moderate to severe OSA more than doubles the risk for microbleeds.1 CMBs are an early marker of cerebral vasculopathy and are associated with increased risk of symptomatic stroke and dementia. The research suggests moderate to severe OSA may be a useful target to help identify incident CMBs and their associated risks in the general population.
“When researchers adjusted to control for a person’s age, weight, diabetes, and high blood pressure, moderate to severe OSA remained an independent risk factor for microbleeds,” said Franco Laghi, MD, Assistant Professor of Pulmonary Medicine at the University of Chicago, who was not involved in the research. “The potential effects of moderate to severe sleep apnea that is not controlled or treated with a CPAP device are concerning. Even if the person does not fit the classic picture of OSA or vasculopathy, this is something to keep in mind and to communicate to patients.”
The findings are not surprising given the associations between OSA and cerebral small vessel disease seen in earlier studies (mostly cross-sectional in nature), said lead author Ali Tanweer Siddiquee, MBBS, PhD, Research Professor at the Institute of Human Genomic Study at Korea University.
“Our findings help consolidate the relationship between OSA and the risk of cerebral microbleeds from long-term longitudinal data at population level,” he explained.
The study, Obstructive Sleep Apnea and Cerebral Microbleeds in Middle-Aged and Older Adults, followed 1,441 participants of the ongoing Korean Genome and Epidemiology Study (KoGES) and the KoGES-Ansan Aging Study subcohort for eight years between 2011 and 2022. All of the participants had in-home polysomnography and structural brain MRI at baseline, four years, and eight years. Apnea was defined as a ≥ 90% reduction in baseline airflow for at least 10 seconds despite ongoing respiratory effort. Hypopnea was defined as a ≥ 30% reduction in airflow for at least 10 seconds with ≥ 4% oxygen desaturation.
The mean age of participants was 57.75 years at baseline. More than half the participants (52.67%) were female, 30.35% had mild OSA, 13.39% had moderate to severe OSA, and 56.26% had no OSA. The moderate to severe group was predominately male (70.47%) and had significantly higher BMI (26.11) compared with the mild (25.28) or no (23.94) OSA groups. There was no difference in self-reported routine physical activity between the groups, but the moderate to severe group had more individuals who reported current tobacco smoking and alcohol use. The moderate to severe group also had higher prevalences of hypertension and diabetes.
Compared with the non-OSA group, the moderate to severe OSA group had higher unadjusted RR at both four years (RR, 2.52; 95% CI, 1.12-5.68; P = .02) and eight years (RR, 2.18; 95% CI, 1.16-4.08; P = .01) of follow-up.
After adjusting for age, sex, educational level, BMI, physical activity, smoking, alcohol use, total and low-density lipoprotein cholesterol, hypertension, diabetes, and age-related white matter change, CMB risk was similar at four years (RR, 2.52; 95% CI, 1.07-5.92; P = .03) and eight years (RR, 2.04; 95% CI, 1.04-3.99; P = .03), respectively.
Adding adjustments for change in apnea-hypopnea index (AHI), change to BMI, and mean arterial pressure, the moderate to severe OSA group had no increased risk for CMB at four years; but, at eight years, the RR was 2.14 (95% CI, 1.08-4.23; P = .02). The mild OSA group had no increased CMB risk at any observed point.
Given these findings, Dr. Laghi said he would feel even more inclined to prescribe a CPAP device for moderate sleep apnea, as even individuals in the 15 to 30 AHI range showed an increased microbleed risk.
“For AHI higher than 30, severe sleep apnea, I would definitely do it,” he added. “This is the first piece of prospective literature to show these significant differences, a stepping stone to future work. This is an exciting development for future collaborations among authors and researchers as well as for clinicians and patients.”
Notably, this research does not demonstrate that treating OSA can prevent microbleeds. However, treating OSA remains important in modifying other downstream consequences of OSA.
References
1. Siddiquee AT, Hwang YH, Kim S, et al. Obstructive sleep apnea and cerebral microbleeds in middle-aged and older adults. JAMA Netw Open. 2025;8(10):e2539874. doi:10.1001/jamanetworkopen.2025.39874
