Vascular contributions to cognitive impairment/dementia in diabetes: role of endothelial cells and pericytes

Vascular contributions to cognitive impairment/dementia (VCID) are a leading cause of dementia, a known neurodegenerative disorder characterized by progressive cognitive decline. Although diabetes increases the risks of stroke and the development of cerebrovascular disease, the cellular and vascular mechanisms that lead to VCID in diabetes are yet to be determined. A growing body of research has identified that cerebrovascular cells within the neurovascular complex display an array of cellular responses that impact their survival and reparative properties, which plays a significant role in VCID development. Specifically, endothelial cells and pericytes are the primary cell types that have gained much attention in dementia-related studies due to their molecular and phenotypic heterogeneity. In this review, we will discuss the various morphological subclasses of endothelial cells and pericytes as well as their relative distribution throughout the cerebrovasculature. Furthermore, the use of diabetic and stroke animal models in preclinical studies has provided more insight into the impact of sex differences on cerebral vascularization in progressive VCID. Understanding how cellular responses and sex differences contribute to endothelial cell and pericyte survival and function will set the stage for the development of potential preventive therapies for dementia-related disorders in diabetes.