Vascular Cognitive Impairment and Dementia : From Pathophysiological Mechanisms to Emerging Therapeutic Strategies

Vascular Cognitive Impairment and Dementia (VCID) is a major, potentially preventable cognitive decline that emerges from cerebrovascular dysfunction, influenced predominantly by aging and metabolic disorders. VCID represents a significant cause of dementia worldwide. VCID arises from heterogeneous cerebrovascular pathologies, including cerebral small and large vessel disease and chronic cerebral hypoperfusion. Therapeutic progress in VCID remains constrained by pathological heterogeneity, frequent overlap with mixed neurodegenerative dementia, limited availability of sensitive early biomarkers, and a persistent shortage of VCID-specific randomized trials validating disease-modifying interventionsThis review summarizes recent diagnostic concepts, mechanistic pathways, and preventive and potential therapeutic interventions in managing VCID. Key mechanisms in pathophysiology of VCID include vascular endothelium disruption and loss of blood–brain barrier integrity, which facilitate oxidative stress and neuroinflammation. These processes impair neurovascular coupling and drive the white-matter injury, disconnecting cortical and subcortical pathways, and subsequent cognitive dysfunction. Hypertension remains the most robust modifiable risk factor, with metabolic disorders, chronic kidney disease, aging, and stroke further accelerating vascular brain injury. Although current management largely focuses on vascular risk reduction, emerging disease-modifying approaches, including senolytics and mitochondrial boosters, necessitate the evaluation in clinical settings. Future progress in VCID management depends on detection of sensitive biomarkers, and phase III clinical trials targeting neurovascular repair.