Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia

Abstract

Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer's disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword "vascular dementia" was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer's dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies' investment in new drugs targeting VCI and vascular dementia remains insufficient.

Keywords: clinical trial; vascular cognitive impairment; vascular dementia.

Figure 1

Progression of the pathophysiology of vascular cognitive impairment (VCI) or vascular dementia (VaD). BBB, blood–brain barrier.

Figure 2

Drug development pipeline in VCI or VaD treatment. The agents are displayed using specific shapes corresponding to their pathophysiological mechanisms. BBB, blood–brain barrier; BPSD, behavioral and psychological symptoms of dementia.

Figure 3

VCI and VaD drug development between 2007 and 2022 (registered on ClinicalTrials.gov accessed on 20 May 2022).

Figure 4

Flowchart of trial selection from a search of ClinicalTrials.gov accessed on 20 May 2022.