Association of obstructive sleep apnea and cerebral small vessel disease: a systematic review and meta-analysis

Sleep. 2020 Apr 15;43(4):zsz264. doi: 10.1093/sleep/zsz264.


Study objectives: The objective of the present study was to investigate the association between obstructive sleep apnea (OSA) and the presence of various neuroimaging marker of cerebral small vessel disease (CSVD).

Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane library (from inception to May 2019) for studies evaluating the association between OSA and CSVD, which included white matter hyperintensities (WMH), silent brain infarction (SBI), cerebral microbleeds (CMBs), and perivascular spaces (PVS). Pooled odds ratios (ORs) with 95% confidence interval (CIs) were estimated using random-effects meta-analysis.

Results: After screening 7290 publications, 20 studies were finally included involving 6036 subjects. The sample size ranged from 27 to 1763 (median 158, interquartile range: 67-393). The meta-analysis showed that moderate to severe OSA was positively associated with WMH (13 studies, n = 4412, OR = 2.23, 95% CI = 1.53 to 3.25, I2 = 80.3%) and SBI (12 studies, n = 3353, OR 1.54, 95% CI = 1.06 to 2.23, I2 = 52%). There was no association with CMBs (three studies, n = 342, OR = 2.17, 95% CI = 0.61 to 7.73, I2 = 60.2%) or PVS (two studies, n = 267, OR = 1.56, 95% CI = 0.28 to 8.57, I2 = 69.5%). There was no relationship between mild OSA and CSVD.

Conclusion: Current evidence suggests that moderate to severe sleep apnea is positively related to WMH and SBI, but not CMBs or PVS, which suggests that OSA may contribute to the pathogenesis of CSVD. Further large cohort studies should be prioritized to confirm the findings.

Keywords: cerebral microbleeds; cerebral small vessel disease; obstructive sleep apnea; silent brain infarction; white matter hyperintensities.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Biomarkers
  • Cerebral Small Vessel Diseases* / complications
  • Cerebral Small Vessel Diseases* / diagnostic imaging
  • Cerebral Small Vessel Diseases* / epidemiology
  • Humans
  • Magnetic Resonance Imaging
  • Neuroimaging
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / epidemiology


  • Biomarkers