Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Apr 19;103(16):e37799.
doi: 10.1097/MD.0000000000037799.

Evaluating the efficacy and safety of Alzheimer's disease drugs: A meta-analysis and systematic review

Yan Chen  1 , Min Lai  1 , Ming Tao  2
Affiliations
Meta-Analysis

Evaluating the efficacy and safety of Alzheimer's disease drugs: A meta-analysis and systematic review

Yan Chen et al. Medicine (Baltimore). .

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.

Objective: The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.

Methods: We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.

Results: All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.

Conclusion: ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Flowchart describing the approach used to identify all eligible studies of meta-analysis.
Figure 2.
Figure 2.
(A) Cognitive outcomes on the ADAS–cog subscale (change from baseline) in AD patients in cholinesterase inhibitors, memantine, and GV-971 trials; (B) Global change outcomes on the CIBIC + scale (change from baseline) in AD patients in cholinesterase inhibitors, memantine, and GV-971 trials; (C) Behavior outcomes on the NPI scale (change from baseline) in AD patients in cholinesterase inhibitors, memantine, and GV-971 trials; (D) Functional outcomes on the ADCS/ADL subscale (change from baseline) in AD patients in cholinesterase inhibitors, memantine and GV-971 trials.
Figure 3.
Figure 3.
(A) Safety outcomes comparison on any reason caused dropouts in cholinesterase inhibitors, memantine, and GV-971 trials; (B) Safety outcomes comparison on adverse events caused dropouts in cholinesterase inhibitors, memantine, and GV-971 trials.
Figure 4.
Figure 4.
Forest plots of all adverse events.
Figure 5.
Figure 5.
The molecular docking of donepezil.
Figure 6.
Figure 6.
The molecular docking of galantamine.
Figure 7.
Figure 7.
The molecular docking of rivastigmine.
Figure 8.
Figure 8.
The molecular docking of memantine.
None
See this image and copyright information in PMC

References

    1. Sengupta U, Nilson AN, Kayed R. The Role of Amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine. 2016;6:42–9. - PMC - PubMed
    1. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s Disease: causes and treatment. Molecules. 2020;25:5789. - PMC - PubMed
    1. Davis M, T OC, Johnson S, et al. . Estimating Alzheimer’s Disease progression rates from normal cognition through mild cognitive impairment and stages of Dementia. Curr Alzheimer Res. 2018;15:777–88. - PMC - PubMed
    1. Sperling RA, Aisen PS, Beckett LA, et al. . Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280–92. - PMC - PubMed
    1. Asher S, Priefer R. Alzheimer’s disease failed clinical trials. Life Sci. 2022;306:120861. - PubMed

MeSH terms