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.