Cited by 171Dementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatments

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Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: a network meta-analysis of 41 randomized controlled trials

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Dou, Kai-Xin, Tan, Meng-Shan, Tan, Chen-Chen, Cao, Xi-Peng, Hou, Xiao-He, Guo, Qi-Hao, Tan, Lan, Mok, Vincent, Yu, Jin-Tai·2018·Alzheimer's Research & Therapy

Abstract

Cholinesterase inhibitors and memantine have been approved for management of Alzheimer’s disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs. We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis. Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference – 0.51, 95% credible interval – 0.67 to − 0.35), galantamine 24 mg daily (− 0.50, − 0.61 to − 0.40), and donepezil 10 mg daily (− 0.40, − 0.51 to − 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm 2 patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis. Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms.

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Crossref · 10.1186/s13195-018-0457-9

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Figures

Fig. 1 Flow diagram of study selection
Fig. 1 Flow diagram of study selectionCC BY · PubMed Central
Fig. 2 Network of eligible comparisons of cognition for mild to moderate AD (a) and moderate to severe AD (b). Width of lines proportional to number of trials comparing every pair of treatments, and size of every node proportional to number of randomly assigned participants (sample size). DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmine
Fig. 2 Network of eligible comparisons of cognition for mild to moderate AD (a) and moderate to severe AD (b). Width of lines proportional to number of trials comparing every pair of treatments, and size of every node proportional to number of randomly assigned participants (sample size). DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmineCC BY · PubMed Central
Fig. 3 Comparative efficacy and tolerability for mild to moderate AD in the network meta-analysis: comparisons should be read from left to right. Efficacy and tolerability estimate located at intersection of column-defining treatment and row-defining treatment. For efficacy (mean changes of cognition), SMD < 0 favors column-defining treatment. For tolerability (all-cause adverse events), OR < 1 favors row-defining treatment. Significant results bold and underlined. CrI credible interval, DON donepezil, GAL galantamine, MEM memantine, OR odds ratio, PBO placebo, RIV rivastigmine, SMD standardized mean difference
Fig. 3 Comparative efficacy and tolerability for mild to moderate AD in the network meta-analysis: comparisons should be read from left to right. Efficacy and tolerability estimate located at intersection of column-defining treatment and row-defining treatment. For efficacy (mean changes of cognition), SMD < 0 favors column-defining treatment. For tolerability (all-cause adverse events), OR < 1 favors row-defining treatment. Significant results bold and underlined. CrI credible interval, DON donepezil, GAL galantamine, MEM memantine, OR odds ratio, PBO placebo, RIV rivastigmine, SMD standardized mean differenceCC BY · PubMed Central
Fig. 4 Rank for efficacy on cognition (solid line) and tolerability (dotted line) for mild to moderate AD. Ranking (x axis) indicates probability to be best treatment, second best, third best, and so on. DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmine
Fig. 4 Rank for efficacy on cognition (solid line) and tolerability (dotted line) for mild to moderate AD. Ranking (x axis) indicates probability to be best treatment, second best, third best, and so on. DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmineCC BY · PubMed Central
Fig. 5 Forest plots of network meta-analysis of efficacy on function (a) and global changes (b) compared with placebo. SMD standardized mean difference, OR odds ratio, CrI credible interval
Fig. 5 Forest plots of network meta-analysis of efficacy on function (a) and global changes (b) compared with placebo. SMD standardized mean difference, OR odds ratio, CrI credible intervalCC BY · PubMed Central

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Research works printed but not linked: 1

  1. NICE. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. London: National Institute for Health and Care Excellence; 2011.

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Metadata

Authors
Dou, K.-X., Tan, M.-S., Tan, C.-C., Cao, X.-P., Hou, X.-H., Guo, Q.-H., Tan, L., Mok, V., & Yu, J.-T.
Affiliations
  • Qingdao University (CN)
  • Fudan University (CN)
  • Chinese University of Hong Kong (HK)
Corresponding author
  • Tan, Lan
  • Yu, Jin-Tai
Venue
Alzheimer's Research & Therapy
Published
2018-12
Volume
10
Issue
1
Pages
126-126
ISSN
1758-9193 (ISSN-L)
OpenAlex
W2907817008
Cited by
171
References
41
Citations by year
2026: 15 · 2025: 24 · 2024: 24 · 2023: 31 · 2022: 28 · 2021: 22 · 2020: 16 · 2019: 11
FWCI
1.86
Type
journal article
Language
en
Open access
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, cholinesterase inhibitors, memantine, galantamine, donepezil, rivastigmine, cognitive function, drug efficacy, drug safety, tolerability, neuropsychiatric symptoms, disease severity, combination therapy
MeSH terms
Network Meta-Analysis, Alzheimer Disease, Cholinesterase Inhibitors, Female, Humans, Male, Memantine, Randomized Controlled Trials as Topic, Treatment Outcome, Nootropic Agents

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