Taken together, we conclude that T1D causes increased mitochondrial complex III ROS production, DNA damage, and Chk2 phosphorylation in CASMC, thereby leading to vascular dementia in both male and female mice; our results further demonstrate that mitochondrial complex III ROS-mediated DNA damage is more significant in male than female mice, which contributes to more serious vascular dementia in the former than the latter. The gene discussed is CHEK2; the disease is vascular dementia.