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

Author:

Lam Bonnie Yin Ka123ORCID,Cai Yuan1,Akinyemi Rufus4567ORCID,Biessels Geert Jan8ORCID,van den Brink Hilde8,Chen Christopher9,Cheung Chin Wai1ORCID,Chow King Ngai1,Chung Henry Kwun Hang1,Duering Marco11011ORCID,Fu Siu Ting1,Gustafson Deborah12,Hilal Saima91314,Hui Vincent Ming Ho12,Kalaria Rajesh7,Kim SangYun15,Lam Maggie Li Man1,de Leeuw Frank Erik16,Li Ami Sin Man12ORCID,Markus Hugh Stephen17ORCID,Marseglia Anna18,Zheng Huijing12,O’Brien John19,Pantoni Leonardo20ORCID,Sachdev Perminder Singh21ORCID,Smith Eric E22ORCID,Wardlaw Joanna23ORCID,Mok Vincent Chung Tong12

Affiliation:

1. Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong

2. Gerald Choa Neuroscience Institute, Margaret K.L. Cheung Research Centre for Management of Parkinsonism, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong

3. Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

4. Neuroscience and Ageing Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria

5. Centre for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria

6. Department of Neurology, University College Hospital, Ibadan, Nigeria

7. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

8. Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands

9. Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

10. Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany

11. Medical Image Analysis Center (MIAC), Department of Biomedical Engineering, University of Basel, Basel, Switzerland

12. Section for NeuroEpidemiology, Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA

13. Memory, Aging and Cognition Center, National University Health System, Singapore

14. Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore

15. Clinical Neuroscience Center, Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea

16. Donders Institute for Brain Cognition and Behaviour, Department of Neurology, Radboudumc, Nijmegen, The Netherlands

17. Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

18. Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden

19. Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK

20. Stroke and Dementia Lab, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

21. School of Psychiatry, Neuropsychiatric Institute, The University of New South Wales, Sydney, NSW, Australia

22. Division of Neurology, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

23. Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK

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.

Funder

Wellcome Trust

MACS/WIHS Combined Cohort Study (MWCCS): Brooklyn Clinical Research Site

NIH/National Heart, Lung and Blood Institute

UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK

Lee Hysan Postdoctoral Fellowship in Clinical Neurosciences

Royal Society and African Academy of Sciences

Publisher

SAGE Publications

Subject

Neurology

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