Advances in pharmacotherapy for vascular cognitive impairment and vascular dementia: An update of 2025

Vascular cognitive impairment (VCI), including vascular dementia (VaD), encompasses a spectrum of cognitive deficits resulting from cerebrovascular pathology, ranging from mild impairment to dementia. As the second leading cause of dementia worldwide, VCI remains a major therapeutic challenge. A comprehensive search of ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) identified randomized controlled trials (RCTs) conducted or completed between 2012 and 2025. Trials enrolling participants diagnosed with VCI or VaD across all disease stages and all trial phases were included. Forty-one RCTs met the inclusion criteria encompassing diverse therapeutic mechanisms. Investigated agents included neuroprotective and vascular-targeted compounds, neurotransmitter modulators, symptom-focused drugs for behavioral and psychological symptoms of dementia (BPSD), traditional Chinese medicine (TCM) formulations, and agents acting on novel pathways. Recent trials in VCI and VaD show increasing methodological rigor and therapeutic diversity, signaling growing research momentum in the field. Nonetheless, progress is constrained by regional concentration of studies, limited publication of completed results, and inconsistent disease classification across stages. Strengthening global collaboration, ensuring transparent reporting, and standardizing disease staging will be critical to advancing pharmacological development for vascular cognitive disorders.