Efficacy Of Donepezil For Vascular Dementia And The Dose Correlation:a Meta-analysis

BackgroundVasculer dementia (VaD) is a syndrome caused by cerebrovascular lesions involving functionally important brain areas responsible for memory、cognition and behavior, which is the second most common type of dementia following AD. Along with global aging, the morbidity of VaD is rising. VaD seriously influenses the quality of the patients’life, and brings their families heavy burdens. It also brings a big challenge to the society. The cure of VaD is urgent. Therefore, people have turned their attention to effective medicine. A meta-analysis of several randomized controlled trials made by Richard A Hansen demonstrate that cholinesterase inhibitor(CHEI) is effective for mild and moderate Alzheimer’s disease(AD). Clinical evidence indicates that a cholinergic deficit, similar to that seen in AD, is associated with VaD, suggesting that patients with VaD may benefit from treatment with CHEI.The CHEI donepezil, is indicated for the treatment of AD, but if it can bring a benefit to patients with VaD still remains a dispute. There is considerable evidence regarding the efficacy of donepezil for patients with VaD. However, due to lack of sufficient evidence, there is still doubt about the answer. In the present study, we performed a meta-analysis to evaluate the efficacy of donepezil for the treatment of VaD and the dose correlation. ObjectiveTo evaluate the efficacy of donepezil for VaD and the dose correlation.MethodWe searched Pubmed、Cochrane Library、EMbase, using the terms "donepezil and vascular dementia", for relative randomized controlled trials. Information about age, sex, numbers randomized, design, medication doses, least squares mean change from baseline score, and adverse effect was extracted and a meta-analysis was performed by Revman5.1.4.0.ResultFour reports of randomized controlled trials were identified, involving2315patients with probable VaD or possible VaD. Of the2315patients,786were treated with placebo,399with donepezil5mg/day,1130with donepezil10mg/day. The ADAS-cog was used in all trials, which made it possible for our study. The result showed that both donepezil5mg/day(WMD-1.16,95%CI:-1.67—-0.65, P<0.00001) and10mg/day(WMD-2.17,95%CI:-2.97—-1.36. P<0.00001) significantly improved the patients’cognitive function, and there was no significant difference between the two doses(WMD-0.50,95%CI:-1.27—0.28, P=0.21).For functional and behavioral outcomes, only10mg/day donepezil group differed from placebo in functional assessment scores with a difference on the AD Functional Assessment and Change Scale(ADFACS, WMD-0.95,95%CI:-1.73—-0.17, P=0.02), and there was no significant difference between the two doses(WMD-0.21,95%CI:-0.98—0.57, P=0.60). Only5mg/day donepezil group differed from placebo on Mini-Mental State Examination (MMSE, WMD0.53,95%CI:0.18-0.89, P=0.003), and on Clinical Dementia Rating-Sum of Boxes score (CDR-SB), only10mg/day donepezil group differed from placebo(WMD-0.29,95%CI:-0.49—-0.09, P=0.005).ConclusionDonepezil provides small benefits for the treatment of patients’with mild to moderate VaD, and there is no difference in the efficacy between the two doses. Data is not sufficient for the present meta-analysis to support widespread use of donepezil in VaD.