Identifying targets at the blood-brain barrier for treating vascular cognitive impairment and dementia

Vascular cognitive impairment and dementia (VCID) arise from chronic cerebrovascular dysfunction that compromises the blood-brain barrier (BBB), a critical interface maintaining neural homeostasis. The BBB's neurovascular unit (NVU) integrates endothelial cells, pericytes, astrocytes, and neurons, whose coordinated function preserves cerebral integrity. Persistent hypoperfusion, oxidative stress, and inflammation disrupt this system, triggering tight-junction degradation, impaired nutrient transport, and neuroinflammatory cascades that accelerate white matter damage and cognitive decline.

This review examines recent advances linking BBB dysfunction to VCID pathogenesis and summarizes pharmacological, cellular, and technological strategies to restore barrier function. Small molecules targeting oxidative and inflammatory signaling, cell-based therapies (mesenchymal and endothelial progenitors, iPSC-derived lineages), and advanced delivery platforms such as focused ultrasound and nanocarriers are evaluated for their potential to protect or repair the BBB.

Effective VCID management will require precision medicine approaches integrating BBB biomarkers, vascular risk control, and targeted anti-inflammatory or regenerative therapies. Ongoing innovation in imaging, molecular diagnostics, and delivery systems offers a realistic path toward early intervention and prevention of cognitive decline by safeguarding neurovascular integrity.