10 Genetic associations with brain microbleeds: systematic review and meta-analyses

Abstract

Objective: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). Methods:We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of Ͼ100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I 2 and 2 statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. Results:Only the APOE ⑀2/3/4 polymorphism had been studied in Ͼ100 people (10 studies, Conclusions:Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy. Neurology ® 2011;77:158-167 GLOSSARY BMB ϭ brain microbleed; CAA ϭ cerebral amyloid angiopathy; CI ϭ confidence interval; GRE ϭ gradient-recalled echo; HWE ϭ Hardy-Weinberg equilibrium; ICH ϭ intracerebral hemorrhage; OR ϭ odds ratio.Brain microbleeds (BMBs) are minute deposits of blood products, seen as focal areas of signal loss typically Ͻ10 mm in diameter on haem-sensitive T2*-weighted gradient-recalled echo (GRE) MRI sequences. BMBs occur in 5% to 38% of apparently healthy people, increasing in frequency with age, hypertension, and smoking.