Global burden of cerebral small vessel disease determined from large MRI studies: A systematic review and meta-analysis

BACKGROUND: Cerebral small vessel disease (SVD) is a major cause of ischemic stroke, intracerebral hemorrhage, and dementia. Despite its importance, there are few studies of its prevalence and how cerebral SVD varies across the world, different age ranges, sexes, and magnetic resonance imaging (MRI) parameters. SVD can be estimated using MRI neuroimaging markers, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and perivascular spaces (PVS). AIMS: This study aimed to document the global prevalence of SVD based on population-based or large community-based MRI studies and to determine how SVD prevalence varies by region, mean age, and sex. With SVD neuroimaging markers being the standard to assess SVD prevalence, we aimed to investigate how different MRI acquisition parameters may influence its prevalence. SUMMARY OF REVIEW: In this systematic review and meta-analysis, articles were searched from the Ovid MEDLINE and EMBASE databases between 1 January 2000 and 31 March 2024, without language restrictions. Title and abstract screening, full-text review, and data extraction were performed by at least two independent reviewers. The prevalence of SVD, subject demographic information, and MRI acquisition parameters were extracted. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). Of 14,582 studies identified, 246 studies spanning 40 countries were included in the systematic review. In the meta-analysis, 85 studies (88 cohorts) from 17 regions (n = 1,562,765) were included. The quality of studies was high (mean score 7.67 out of 8, ranging between 5 and 8). The pooled prevalence of moderate-to-severe WMH was 18.9%, and the pooled mean of WMH volume was 4.4 mL. Pooled prevalences of lacunes, cerebral microbleeds (CMBs), and moderate-to-severe perivascular spaces (PVS) were 11.2%, 10.3%, and 22.6%, respectively. A lower lacune prevalence (7.3% vs 13.3%; adjusted OR (aOR) [95% confidence interval (CI)]: 0.45 [0.30-0.68]) but higher PVS prevalence (30.9% vs 19.6%; aOR [95% CI]: 12.15 [2.12-69.46]) was found in Europe compared with Asia. A higher mean age of the studies was associated with a higher prevalence of most SVD markers, except for PVS. There was an overall trend of more lacunes and CMBs in males. MRI field strength, sequence used, and slice thickness could potentially influence the reported SVD prevalence, especially for WMH volume and CMB count. There was high heterogeneity in the studies (>95%) that was not resolved by performing analyses stratified by Global Burden of Disease (GBD) regions, age groups, study design, or MRI parameters. CONCLUSION: This systematic review and meta-analysis based on large MRI studies demonstrated that SVD is a common health problem affecting about one-fifth of the adult population. SVD prevalence differs in regions separated by geographical regions. SVD prevalence is higher with increasing age. There is an overall trend of more lacunes and CMBs in males. WMH volume and CMB are SVD markers prone to the variability of MRI acquisition parameters, and a harmonised SVD scanning protocol should be used. More studies from middle- and low-income regions would benefit the estimation of a truly global prevalence of SVD.