Obstructive sleep apnea is associated with markers of cerebral small vessel disease in a dose-response manner: A systematic review and meta-analysis

Cerebral small vessel disease manifests on neuroimaging as white matter hyperintensities, lacunes, cerebral microbleeds, perivascular spaces or subcortical infarcts and is a major contributor to dementia, stroke and incident death. We aimed to determine whether obstructive sleep apnea severity is associated cerebral small vessel disease. A systematic search was conducted for studies examining the association between obstructive sleep apnea and cerebral small vessel disease markers. A random-effects model was used to meta-analyze unadjusted odds ratios derived from event rates. The neuroimaging-derived measures of white matter hyperintensities, lacunes, and cerebral microbleeds were compared against increasing obstructive sleep apnea severity, as measured by apnea-hypopnea indices of <5, 5–15, ≥15 and ≥ 30. Thirty-two observational studies were included: ten reported effect sizes for white matter hyperintensities, nine for lacunes and three for cerebral microbleeds. Compared to patients without obstructive sleep apnea, the odds of possessing white matter hyperintensities were 1.7 [95% confidence interval 0.9–3.6] in mild, 3.9 [2.7–5.5] in moderate-severe and 4.3 [1.9–9.6] in severe obstructive sleep apnea. Moderate-severe obstructive sleep apnea was associated with a higher risk of lacunar infarcts. Obstructive sleep apnea had no association with cerebral microbleeds and an indeterminate association with perivascular spaces and subcortical infarcts due to insufficient data.