Gray matter volume abnormalities in vascular cognitive impairment and their association with gene expression profiles

It has been revealed that brain gray matter volume (GMV) abnormalities are present in patients with vascular cognitive impairment (VCI). However, the GMV alterations that have been uncovered are highly inconsistent, and their correlation with gene expression profiles is still largely unknown. To establish a correlation between VCI-related GMV alterations and gene expression patterns and uncover potential genetic profiles underlying GMV abnormalities in VCI. Here, a quantitative meta-analysis that compared voxel-based GMV between VCI patients and healthy controls (HCs) was carried out on 11 datasets (10 from previous studies and 1 newly collected), comprising 385 VCI individuals and 334 HCs, to investigate GMV alterations in VCI patients. Partial least squares regression analysis was then conducted to investigate the relationship between the GMV alterations in VCI and gene expression profiles obtained from Allen Human Brain Atlas database. Compared with healthy controls, patients with VCI showed consistent decreased GMV which predominantly included the right insula, right Rolandic operculum, right putamen, right superior temporal gyrus, left medial superior frontal gyrus, and right median cingulate and paracingulate gyri. Meta-regression analysis revealed that decreased GMV in left medial superior frontal gyrus was negatively correlated with Mini-Mental State Examination score in VCI. Furthermore, 2,835 genes were identified whose expression patterns were correlated with VCI-related GMV changes, and these genes were enriched in distinct biological processes, brain cell types and lifespan windows across brain regions. Together, these findings could provide the potential neurobiological underpinnings and the genetic substrates underlying GMV abnormalities of VCI.