Distribution of cerebral microbleeds in the East and West: Individual participant meta-analysis

Abstract

Objective: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations.

Methods: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-free participants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial [D/I], or mixed [i.e., CMBs located in both lobar and D/I regions]). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution.

Results: Among 8,595 stroke-free individuals (mean age [SD] 66.7 [5.6] years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval [CI] 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31).

Conclusions: Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.

Figure 1. Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data (PRISMA-IPD) flow diagram

The search of electronic databases (PubMed between January 1, 1996, and April 30, 2014: no articles identified through other sources), using English and Japanese language limit, performed by 2 authors (Y.Y. and A.C.), yielded 39 publications. After 23 duplicates were removed, we identified 16 potential articles. Of those that were reviewed in full-text, we invited 13 independent studies for collaboration with providing individual data. Finally, we included 11 studies that could provide individual data. CMB = cerebral microbleed; IPD = individual participant data. *Additional data (n = 296) were provided by the corresponding author of the publication.

Figure 2. Frequency distribution of participants by age between the Eastern population and Western population (all collected data of 13,985 participants)

Blue bars indicate participant number of Eastern population (per years of age). Red bars indicate participant number of Western population (per years of age). Arrows indicates age range in primary analysis (upper) and in sensitivity analysis (lower).

Figure 3. Forest plots of prevalence of APOE4 carriers made with metadata obtained from published or unpublished metadata

^a Published data of participants with ambulatory blood pressure monitoring in the related cohort study. ^b Unpublished data provided from coauthor (D.D.). ^c Unpublished data provided from coauthor (L.J.L.). ^d Unpublished data (including participants with previous stroke/1 TIA) provided from coauthor (V.S.). ^e Published data.^, CI = confidence interval; ES = effect size.