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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

The efficacy and safety of post-stroke cognitive impairment therapies: an umbrella review

“…In all, 31 studies were excluded due to the following reasons: samples overlap with other studies ( n = 7), no necessary sample data ( n = 10), other outcomes ( n = 4), other PSCI ( n = 3), not written in English ( n = 4), and no placebo group ( n = 3) ( Figure 1 ). Thus, 19 studies were included in the umbrella review: Kim and Kang, (2020) , Guekht et al (2017) , Kwon (2019) , Huang et al (2021) , Tan (2015) , Jin and Liu (2019) , Shi et al (2022) , Lopez-Arrieta and Birks (2002) , Fan (2021) , Yi et al (2020) , Alvarez-Sabín. (2013) , Huahui and Hehua (2015) , Malykh and Sadaie (2010) , Ming (2016) , NanZhu et al (2018) , Wei (2020) , You et al (2019) , Szatmári and Whitehouse (2009) , Szatmari and Whitehouse (2003) .…”

Butylphthalide combined with donepezil for the treatment of vascular dementia: a meta-analysis

“…For example, 10 mg of donepezil has a significantly higher risk of discontinuation related to adverse reactions than a 5-mg dose of donepezil. 5 In China, traditional Chinese medicine is one of the most important supplementary treatments for patients with vascular dementia. 6 Many randomized controlled trials (RCTs) have shown that Chinese patent medicines or Chinese herbal extracts can further improve the cognitive abilities and dementia symptoms of vascular dementia patients in combination with donepezil treatment.…”

Physical Exercise Counteracts Aging-Associated White Matter Demyelination Causing Cognitive Decline

“…Conversely, there is no FDA approved drug for the treatment of VaD. Several AD drugs, such as cholinesterase inhibitors and memantine, were evaluated in clinical trials of VaD, but only marginal positive outcomes were obtained [8][9][10][11]. Altogether, the current situation of pharmacotherapy for SD remains unsatisfactory and requires further development.…”