Perivascular spaces and their associations with risk factors, clinical disorders and neuroimaging features: A systematic review and meta-analysis

Background: Perivascular spaces, visible on brain magnetic resonance imaging, are thought to be associated with small vessel disease, neuroinflammation, and to be important for cerebral hemodynamics and interstitial fluid drainage. Aims: To benchmark current knowledge on perivascular spaces associations with risk factors, neurological disorders, and neuroimaging lesions, using systematic review and meta-analysis. Summary of review: We searched three databases for perivascular spaces publications, calculated odds ratios with 95% confidence interval and performed meta-analyses to assess adjusted associations with perivascular spaces. We identified 116 relevant studies (n = 36,108) but only 23 (n = 12,725) were meta-analyzable. Perivascular spaces assessment, imaging and clinical definitions varied. Perivascular spaces were associated (n; OR, 95%CI, p) with ageing (8395; 1.47, 1.28-1.69, p = 0.00001), hypertension (7872; 1.67, 1.20-2.31, p = 0.002), lacunes (4894; 3.56, 1.39-9.14, p = 0.008), microbleeds (5015; 2.26, 1.04-4.90, p = 0.04) but not WMH (4974; 1.54, 0.71-3.32, p = 0.27), stroke or cognitive impairment. There was between-study heterogeneity. Lack of appropriate data on other brain disorders and demographic features such as ethnicity precluded analysis. Conclusions: Despite many studies, more are required to determine potential pathophysiological perivascular spaces involvement in cerebrovascular, neurodegenerative and neuroinflammatory disorders.