Longevity & AgingFixing the Brain's Blood Vessels Could Unlock New Dementia Treatments
Vascular cognitive impairment and dementia (VCID) is a leading cause of late-life cognitive decline, yet no approved disease-modifying therapies exist. This review argues that dysfunction of the neurovascular unit — involving small vessel disease, blood-brain barrier breakdown, chronic low blood flow, and neuroinflammation — is the central mechanism driving VCID across its many forms. The authors synthesize current pathobiology and highlight emerging therapeutic strategies aimed at restoring neurovascular health, including endothelial stabilization and reducing vascular inflammation. As a case study, they present preclinical evidence for Mas receptor agonism using PNA5, a glycosylated angiotensin-(1-7) analogue, as a promising vascular-focused approach. The review also addresses how better biomarkers and patient stratification could improve early clinical trial design for this underserved condition.
