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.

Drug Discovery and Development Targeting Dementia

“…Moreover, many biological targets and signaling pathways are involved in the pathology of dementia. There is substantial literature that focuses on drug targets for AD [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ], LBD [ 74 , 75 , 76 , 77 ], FTD [ 78 , 79 , 80 , 81 ], and VD [ 82 , 83 , 84 ]. As a result of a better understanding of the biochemical regulation of the mechanisms leading to dementia, new molecular targets have been introduced into clinical trials ( Table 3 ).…”

Effect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis

“…[1,2] Patients often experience a certain degree of behavioral changes, decreased attention and memory, and cognitive impairment. [2,3] If the patient does not receive timely and effective intervention, the neurological function will be further affected as the condition progresses, leading to motor, sensory, and perceptual disorders, which greatly affects the patient's quality of life. [1][2][3] Currently, butylphthalide is commonly used in clinical practice to treat patients with vascular dementia.…”

“…[2,3] If the patient does not receive timely and effective intervention, the neurological function will be further affected as the condition progresses, leading to motor, sensory, and perceptual disorders, which greatly affects the patient's quality of life. [1][2][3] Currently, butylphthalide is commonly used in clinical practice to treat patients with vascular dementia. It has a certain vasodilatory effect, can effectively regulate the blood circulation status of the cardiovascular and cerebrovascular systems, increases the blood flow of the cerebral blood supply arteries, and regulates mitochondrial function.…”

“…[1,2] Patients often experience a certain degree of behavioral changes, decreased attention and memory, and cognitive impairment. [2,3] If the patient does not receive timely and effective intervention, the neurological function will be further affected as the condition progresses, leading to motor, sensory, and perceptual disorders, which greatly affects the patient’s quality of life. [1–3]…”

Treadmill Exercise Prevents Recognition Memory Impairment in VD rat model through Enhancement of Hippocampal Structural Synaptic Plasticity

“…It was mentioned as early as 1980's that VD at present may be more amenable to prevention and treatment than AD [7] . Until now, many more drugs exerts memory protective effects in VD patients, including donepezil and tanzhi granules, targeted the amelioration of cognitive impairment by inhibiting neuroinflammation and acetylcholinesterase [8] . But the drug's side effects can include drug dependence and depression.…”