Genetics of Vascular Dementia: Systematic Review and Meta-Analysis

Background: Vascular dementia (VaD) is the second most common type of dementia. So far, little is known about the contribution of genetic polymorphisms to the risk of VaD. Many candidate genetic polymorphisms have been examined in a large number of studies. However, due to the conflicting results, the genetics of VaD is still behind the shadow. Objective: We conducted a comprehensive meta-analysis on associations between genetic polymorphisms of any gene and VaD to investigate the genetics of VaD. Method: We sought the published studies of associations between any genetic polymorphism and VaD and critically appraised them. We assessed the effects of genetic models by calculating pooled odds ratios (ORs), investigating the origin of heterogeneity by subgroup analysis, and testing the robustness by random effect model and sensitivity analysis. Results: 69 studies with 4,462 cases and 11,583 controls were included. We identified APOE epsilon 2/epsilon 3/epsilon 4 and additional four genetic polymorphisms including MTHFR C677T, PON1 L55M, TGF-beta 1 + 29C/T, and TNF-alpha -850C/T associated with VaD. Tested by random effect model and sensitivity analysis, the pooled results show nice robustness. Conclusions: Our comprehensive meta-analysis highlighted the genetic contribution to sporadic VaD. Because of the small amount of data on associations between genetic polymorphisms, except for APOE, and VaD, more studies are needed to test the existing genetic polymorphisms and detect other related genetic variants.