Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment

Dementia is a large and growing health problem in developed and developing countries, with total costs approaching 1% of global gross domestic product, threatening the sustainability of healthcare systems.1 There are currently no disease‐modifying treatments for the most common cause of dementia, Alzheimer disease (AD). The second most common contributor to dementia risk is cerebrovascular disease.2 In contrast to AD, there is greater hope that vascular contributions to cognitive impairment can be prevented and treated. Recent evidence that the incidence of dementia is declining has prompted speculation, not yet confirmed, that this decline may be partly attributable to improved vascular care.3, 4 In this article, we review trial design and drug development for vascular cognitive impairment (VCI), focusing on symptomatic patients with vascular mild cognitive impairment (MCI) or dementia. First, we review axes along which vascular components of cognitive impairment can be addressed, including choice of trial population, trial intervention, and type of outcome. Second, we briefly review the pathophysiology of VCI, introducing the concept that trials may focus on disease modification, improving resilience, or enhancing cognition. Third, we systematically review prior drug trials for VCI patients according to drug class and trial size. Finally, we offer suggestions for methodological improvements for future trials.