From Cerebrovascular Injury to Vascular Cognitive Impairment and Dementia: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles

Vascular cognitive impairment and dementia (VCID) encompass a spectrum of cognitive syndromes ranging from mild cognitive impairment to vascular dementia, accounting for approximately 15-20% of all dementia cases and representing the second most common form of dementia. Despite its high prevalence and clinical burden, effective therapeutic strategies remain lacking. Increasing evidence indicates that vascular dysfunction plays a central role in the pathogenesis of VCID by compromising cerebrovascular integrity, impairing endothelial function, and disrupting neurovascular coupling, which collectively contribute to cognitive decline. Stem cells have emerged as promising candidates for promoting vascular repair and neurovascular coupling. Notably, extracellular vesicles (EVs) derived from stem cells exert reparative and protective effects by transferring bioactive molecules that enhance endothelial function and preserve the blood-brain barrier (BBB) function to affected regions. This review summarizes the current knowledge of VCID from a vascular perspective, highlights recent advances in understanding stem cells and their derived EVs in promoting vascular repair and alleviating cognitive decline, and discusses future directions for translating these insights into innovative therapeutic strategies for VCID.