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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. [ABSTRACT FROM AUTHOR]

Importance: Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce., Objective: To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex., Design, Setting, and Participants: This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023., Main Outcomes and Measures: Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death., Results: A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences., Conclusions and Relevance: This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

Introduction: The benefit and risk of aerobic exercise among older people harboring advanced cerebral small vessel disease (CSVD) upon cognition, mood, and motor functions are unknown., Methods: This rater-blind randomized trial examined effects of a 24-week aerobic exercise training (60 min/session, twice/week) upon clinical (cognition, mood, motor functions) and hemodynamic (pulse pressure [PP], blood pressure [BP], pulsatility index) measures in older people harboring moderate to severe CSVD, as evidenced by confluent white matter hyperintensity and/or ≥2 lacunes on magnetic resonance imaging. We further investigated interactions between treatment conditions and hemodynamics measures., Results: Fifty-three and 54 subjects were randomized into the active and control group, respectively. There was no between-group difference in any of the clinical outcomes. The active group had a greater between-group reduction in systolic BP and PP than the control group. Within-group comparison showed that global cognition of the active group remained similar at end of the study compared to baseline, whereas it declined significantly in the control group. We observed "diverging" interaction effects in that greater reduction in systolic BP/PP was associated with greater improvement in memory functions and global cognition but worsening in processing speed in the active group. Side effects were comparable between the two groups., Discussion: Future study should investigate the mechanisms of the diverging impacts of aerobic exercise upon different cognitive domains so that the benefit-risk ratio of aerobic exercise in older people harboring more advanced CSVD can be better defined., Competing Interests: In the past 36 months, Adrian Wong reports payment from Hong Kong Court (payment made to him). Margaret Kit Yi Mak reports conference attendance support from The Hong Kong Polytechnic University to attend the XXVI World Congress on Parkinson's Disease and Related Disorders May 1–4, 2021. Linda Chiu Wa Lam reports consulting fees from the second expert Colloquium on Early Alzheimer's Disease organized by Eisai Pharmaceutical (zoom meeting in 2020); and giving a lecture and preparing a newsletter article on mental disorders for dentists for the Hong Kong Dental Association (2020); and she is a member of the Advisory Committee on Mental Health at the Food and Health Bureau of the HKSAR government. Sin Ki Yeung reports the provision of reading materials by the professor for the submitted work. Lin Shi reports grants from Hong Kong General Research Fund and Innovation and Technology Fund. Thomas Wai Hong Leung is the president of Hong Kong Neurological Society (unpaid). Yannie Oi Yan Soo reports grants from Hong Kong Health and Medical Research Fund (payment made to CUHK) and Emerging Markets Thrombosis Investigator‐Initiated Research Program from Pfizer (payment made to CUHK); and honorarium for being a speaker from Amgen (payment made to her), honorarium for being a speaker from Daiichi and Boehringer Ingelheim (Hong Kong) Ltd (payment made to CUHK); and support for conference attendance by Hong Kong Neurological and Hong Kong Stroke Societies (no direct payment involved). Timothy Chi Yui Kwok is the director of Jockey Club Centre for positive ageing, Hong Kong; reports honorarium for attending a hearing for guardianship board, Hong Kong; and payment from Hong Kong government for expert report for coroner office; and donation for research (donation made to CUHK). Ho Ko reports grants from Croucher Innovation Award, Collaborative Research Fund of the Research Grants Council, Hong Kong and Area of Excellence Scheme of the Research Grants Council, Hong Kong (payments made to CUHK); and consulting fees from Videns Incorporation Limited. He has patents on the identifications of new potential disease‐modifying therapeutics for Niemann‐Pick disease type C, a method for slowing down brain aging, and new methods for achieving rapid and deep immunostaining. All other authors declare no financial disclosures or conflicts of interest., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)