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

Bonnie Yin Ka Lam; Yuan Cai; Rufus Akinyemi; Geert Jan Biessels; Hilde van den Brink; Christopher Chen; Chin Wai Cheung; King Ngai Chow; Henry Kwun Hang Chung; Marco Duering; Siu Ting Fu; Deborah Gustafson; Saima Hilal; Vincent Ming Ho Hui; Rajesh Kalaria; SangYun Kim; Maggie Li Man Lam; Frank Erik de Leeuw; Ami Sin Man Li; Hugh Stephen Markus; Anna Marseglia; Huijing Zheng; John O'Brien; Leonardo Pantoni; Perminder Singh Sachdev; Eric E Smith; Joanna Wardlaw; Vincent Chung Tong Mok

doi:10.1177/17474930221137019

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

Bonnie Yin Ka Lam, Yuan Cai, Rufus Akinyemi, Geert Jan Biessels, Hilde van den Brink, Christopher Chen, Chin Wai Cheung, King Ngai Chow, Henry Kwun Hang Chung, Marco Duering, Siu Ting Fu, Deborah Gustafson, Saima Hilal, Vincent Ming Ho Hui, Rajesh Kalaria, SangYun Kim, Maggie Li Man Lam, Frank Erik de Leeuw, Ami Sin Man Li, Hugh Stephen MarkusAnna Marseglia, Huijing Zheng, John O'Brien, Leonardo Pantoni, Perminder Singh Sachdev, Eric E Smith, Joanna Wardlaw, Vincent Chung Tong Mok

Research output: Contribution to journal › Review article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	17474930221137019
Journal	International Journal of Stroke
Early online date	25 Oct 2022
DOIs	https://doi.org/10.1177/17474930221137019
Publication status	E-pub ahead of print - 25 Oct 2022

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LMICs_cSVD_prevalence_systematic_review_meta_anaylses_20220930_highlightedAccepted author manuscript, 2.92 MBLicence: Creative Commons: Attribution (CC-BY)

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Lam, B. Y. K., Cai, Y., Akinyemi, R., Biessels, G. J., van den Brink, H., Chen, C., Cheung, C. W., Chow, K. N., Chung, H. K. H., Duering, M., Fu, S. T., Gustafson, D., Hilal, S., Hui, V. M. H., Kalaria, R., Kim, S., Lam, M. L. M., de Leeuw, F. E., Li, A. S. M., ... Mok, V. C. T. (2022). The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis. International Journal of Stroke, 17474930221137019. Advance online publication. https://doi.org/10.1177/17474930221137019

@article{abc04696c2cc4dbfa5b8d6eb5fd5677f,

title = "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.",

author = "Lam, {Bonnie Yin Ka} and Yuan Cai and Rufus Akinyemi and Biessels, {Geert Jan} and {van den Brink}, Hilde and Christopher Chen and Cheung, {Chin Wai} and Chow, {King Ngai} and Chung, {Henry Kwun Hang} and Marco Duering and Fu, {Siu Ting} and Deborah Gustafson and Saima Hilal and Hui, {Vincent Ming Ho} and Rajesh Kalaria and SangYun Kim and Lam, {Maggie Li Man} and {de Leeuw}, {Frank Erik} and Li, {Ami Sin Man} and Markus, {Hugh Stephen} and Anna Marseglia and Huijing Zheng and John O'Brien and Leonardo Pantoni and Sachdev, {Perminder Singh} and Smith, {Eric E} and Joanna Wardlaw and Mok, {Vincent Chung Tong}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). BYKL is supported by the Lee Hysan Postdoctoral Fellowship in Clinical Neurosciences. JW is supported by the UK Dementia Research Institute, which receives its funding from DRI Ltd (funded by the UK Medical Research Council, Alzheimer{\textquoteright}s Society, and Alzheimer{\textquoteright}s Research UK). RK is supported by a grant from the Royal Society and African Academy of Sciences. DG is supported by NIH/National Heart, Lung and Blood Institute (5U01HL146202-03); MACS/WIHS Combined Cohort Study (MWCCS): Brooklyn Clinical Research Site. Publisher Copyright: {\textcopyright} 2022 World Stroke Organization.",

year = "2022",

month = oct,

day = "25",

doi = "10.1177/17474930221137019",

language = "English",

pages = "17474930221137019",

journal = "International Journal of Stroke",

issn = "1747-4930",

publisher = "SAGE Publications",

}

Lam, BYK, Cai, Y, Akinyemi, R, Biessels, GJ, van den Brink, H, Chen, C, Cheung, CW, Chow, KN, Chung, HKH, Duering, M, Fu, ST, Gustafson, D, Hilal, S, Hui, VMH, Kalaria, R, Kim, S, Lam, MLM, de Leeuw, FE, Li, ASM, Markus, HS, Marseglia, A, Zheng, H, O'Brien, J, Pantoni, L, Sachdev, PS, Smith, EE, Wardlaw, J & Mok, VCT 2022, 'The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis', International Journal of Stroke, pp. 17474930221137019. https://doi.org/10.1177/17474930221137019

TY - JOUR

T1 - The global burden of cerebral small vessel disease in low- and middle-income countries

T2 - A systematic review and meta-analysis

AU - Lam, Bonnie Yin Ka

AU - Cai, Yuan

AU - Akinyemi, Rufus

AU - Biessels, Geert Jan

AU - van den Brink, Hilde

AU - Chen, Christopher

AU - Cheung, Chin Wai

AU - Chow, King Ngai

AU - Chung, Henry Kwun Hang

AU - Duering, Marco

AU - Fu, Siu Ting

AU - Gustafson, Deborah

AU - Hilal, Saima

AU - Hui, Vincent Ming Ho

AU - Kalaria, Rajesh

AU - Kim, SangYun

AU - Lam, Maggie Li Man

AU - de Leeuw, Frank Erik

AU - Li, Ami Sin Man

AU - Markus, Hugh Stephen

AU - Marseglia, Anna

AU - Zheng, Huijing

AU - O'Brien, John

AU - Pantoni, Leonardo

AU - Sachdev, Perminder Singh

AU - Smith, Eric E

AU - Wardlaw, Joanna

AU - Mok, Vincent Chung Tong

N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). BYKL is supported by the Lee Hysan Postdoctoral Fellowship in Clinical Neurosciences. JW is supported by the UK Dementia Research Institute, which receives its funding from DRI Ltd (funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK). RK is supported by a grant from the Royal Society and African Academy of Sciences. DG is supported by NIH/National Heart, Lung and Blood Institute (5U01HL146202-03); MACS/WIHS Combined Cohort Study (MWCCS): Brooklyn Clinical Research Site. Publisher Copyright: © 2022 World Stroke Organization.

PY - 2022/10/25

Y1 - 2022/10/25

N2 - 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.

AB - 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.

U2 - 10.1177/17474930221137019

DO - 10.1177/17474930221137019

M3 - Review article

C2 - 36282189

SN - 1747-4930

SP - 17474930221137019

JO - International Journal of Stroke

JF - International Journal of Stroke

ER -

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

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