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

Abstract

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.

Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management

“…Novel insights into sleep and cognition [ 18 ▪▪ , 19 ] suggest that short night sleep (<5 h), poor quality sleep and hypnotics use are associated with an increased risk of dementia in healthy adults [ 153 , 154 ]. Accordingly, moderate to severe sleep apnoea is linked to WMH and silent brain infarctions [ 155 , 156 ▪ ]. Recent findings on the influence of non-REM-sleep in perivascular clearance of metabolites from the brain, with potential impact on neurodegenerative and vascular pathways [ 19 ], raise questions as to whether interventions focused on improving sleep quality could prevent or reverse age-related cognitive decline.…”

Magnetic resonance white matter changes in patients with obstructive sleep apnoea. The subset of the PURE-MIND (Prospective Urban and Rural Epidemiological) cohort study

“…Numerous studies have demonstrated that patients with moderate and severe OSA have a higher prevalence of CSVD than controls or subjects with mild OSA [22][23][24][25][26]. A recently published meta-analysis and systematic reviews confirm that moderate to severe sleep apnoea is independently related to WMH and silent brain infarcts, which strongly suggests that OSA may contribute to the pathogenesis of CSVD [27,28]. In the present study the score of WMHs both in periventricular and subcortical areas was significantly higher in patients with OSA than in the control group.…”

Clinical management of cerebral small vessel disease: a call for a holistic approach

“…Whether unusual sleep patterns increase the risk of SVD lesions is unclear although disordered night-time sleep is associated with brain atrophy and increased daytime sleep is associated with increased PVS on MRI. [ 74 ] Abnormal sleep, such as obstructive sleep apnea, may be associated with more WMH and silent lacunar infarction, [ 75 ] although inability to correct for co-associated factors like smoking and hypertension may have overestimated the association.…”