Genetic dissection of susceptibility to vascular dementia

Abstract

Vascular dementia (VD) is the dementia induced by cerebrovascular lesions with a variety of pathophysiological subtypes. Our knowledge of the genetic mechanism of VD was restricted to a few Mendelian forms of VD. The complexity of sporadic VD caused by individual and interactive genetic effects under various environmental exposures renders it difficult to uncover genetic determinants. Much more effort has been made to identify associations of various candidate genes and to explain the variability of the complex VD than the Mendelian VD. The identified genes, however, explain a small portion of the heritability of VD, and the associations are often controversial in different populations. This makes understanding the genetic architecture of VD more complicated. We studied the genes and their sequence variants associated with susceptibility to VD, and many of the genes were involved in lipid metabolism, angiotensin, and inflammation. We also discussed future directions for the association analysis. Endeavors with various approaches would eventually show the genetic architecture of VD and provide a valuable tool in stratifying patients according to their genotypes. This is the first review to introduce a variety of primary studies that may offer some foundation for the genetics of VD. Psychiatr Genet 21:69-76 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.