Comparative Efficacy and Acceptability of Cholinesterase Inhibitors and Memantine Based on Dosage in Patients with Vascular Cognitive Impairment: A Network Meta-analysis

Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs.PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted.Eleven RCTs were included. Compared with the placebo, in terms of efficacy donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective on the cognition of ADAS-cog; and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits on the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements on CDR-SB and EXIT25, respectively. In terms of acceptability, the memantine behaved as the best.Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg have beneficial effects on cognition, and donepezil 10mg provides beneficial effects on executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but dose-related adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice, in terms of efficacy and safety acceptability.