APOE genotype and MRI markers of cerebrovascular disease

Objective: We aimed to examine the association of APOE e genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds. Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n 5 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis. Results: APOE e4 carrier status and APOE e44 genotype were associated with increasing white matter hyperintensity burden (sample size-weighted z score meta-analysis [meta]-p 5 0.0034 and 0.0030) and presence of cerebral microbleeds (meta odds ratio [OR] 5 1.24, 95% confidence interval [CI] [1.07, 1.43], p 5 0.004, and 1.87 [1.26, 2.78], p 5 0.002), especially lobar. APOE e2 carrier status was associated with increasing white matter hyperintensity load (z score meta-p 5 0.00053) and risk of brain infarct (meta OR 5 1.41[1.09, 1.81], p 5 0.008). Conclusions: APOEe4andAPOEe2 were associated with increasing burden inMRImarkers for both hemorrhagic and ischemic CVD. While the association of APOE e4 with an increased burden of CVD could be partly contributing to the relationship between APOE e4 and AD, APOE e2was associated with MRI markers of CVD in the opposite direction compared to AD.