Research led by Korea University Ansan Hospital reports finding an association between moderate to severe obstructive sleep apnea and increased risk of cerebral microbleeds.
Cerebral microbleeds appear as small lesions on MRI scans and are regarded as early markers of brain damage. Links with symptomatic stroke and dementia have been well documented, with prevalence ranging from 3% in middle age to 23% in older adults.
Known modifiable factors include smoking, hypertension, dyslipidemia, diabetes, and cardiocerebrovascular disease. Previous studies probing sleep apnea and microbleeds have yielded mixed results, suggesting the need for more comprehensive study.
In the study, “Obstructive Sleep Apnea and Cerebral Microbleeds in Middle-Aged and Older Adults,” published in JAMA Network Open, researchers designed a cohort study to investigate whether obstructive sleep apnea severity is associated with risk of incident cerebral microbleeds in late middle-aged adults.
Data came from an ongoing longitudinal cohort of a Korean community with in-home polysomnography sleep monitoring and brain MRI at baseline with two follow-ups.
A total of 1,441 participants without baseline microbleeds or prior cerebrovascular or cardiovascular disease were included after exclusions. Baseline sleep apnea categories included 812 with no obstructive sleep apnea, 436 with mild obstructive sleep apnea, and 193 with moderate to severe obstructive sleep apnea.
Ranking apnea severity and MRI scans
Overnight in-home sleep monitoring defined apnea-hypopnea index categories as 0–4.9 events per hour (no sleep apnea), 5.0–14.9 events per hour (mild), and 15.0 or more events per hour (moderate to severe).
Cerebral microbleeds were identified as focal areas smaller than 10 mm with very low signal as scored by a radiologist blinded to sleep apnea status.
Who is at risk?
Cumulative incidence at four years reached 1.85% in the non–obstructive sleep apnea group, 1.61% in mild obstructive sleep apnea, and 4.66% in moderate to severe obstructive sleep apnea.
Cumulative incidence at eight years reached 3.33% in the non–obstructive sleep apnea group, 3.21% in mild obstructive sleep apnea, and 7.25% in moderate to severe obstructive sleep apnea.
Multivariable models showed increased risk for moderate to severe obstructive sleep apnea compared with no obstructive sleep apnea at eight years, with relative risk more than twice that of other groups.
Analyses indicated no significantly increased risk at four years in the fully adjusted model and no significantly increased risk for mild obstructive sleep apnea at any time point.
Is it genetic?
Researchers examined whether a genetic factor known to influence cerebrovascular vulnerability, APOE-?4 carrier status, might alter the observed association between obstructive sleep apnea and cerebral microbleeds. Among 1,233 participants with complete genetic data, 18.98% were carriers.
When investigators added APOE-?4 status to the multivariable model, the association between moderate to severe sleep apnea and incident microbleeds relative risk rose slightly to 2.91 compared with 2.14 in the full cohort.
Persistence of the association after accounting for APOE-?4 suggests that the link between moderate to severe obstructive sleep apnea and cerebral microbleeds cannot be explained by genetic predisposition alone, though it could be an added vulnerability.
Findings indicate that moderate to severe obstructive sleep apnea is independently associated with incident cerebral microbleeds and that this association increases over time.
Authors suggest that obstructive sleep apnea represents a modifiable target for early diagnosis and treatment with the goal of preventing microbleeds and potentially reducing future stroke and dementia burden in aging populations.
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More information:
Ali Tanweer Siddiquee et al, Obstructive Sleep Apnea and Cerebral Microbleeds in Middle-Aged and Older Adults, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.39874
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