The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis

Abstract

Background: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed.

Aim: This study aims to systematically review the prevalence of cSVD in LMICs.

Results: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented.

Conclusions: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

Keywords: Cerebral small vessel disease; cerebral microbleed; lacunes; low- and middle-income countries; meta-analysis; perivascular space; prevalence; systematic review; white matter hyperintensities.