A voxel-based morphometric study of cortical gray matter volume changes in Alzheimer’s disease with white matter hyperintensities

White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer’s disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p < 0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p < 0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.