SynthesisBMC neurology2025
Efficacy of acetylcholinesterase inhibitors on reducing hippocampal atrophy rate: a systematic review and meta-analysis.
Synthesis in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Plant-derived phytochemicals for Alzheimer's disease: mechanisms of action, experimental evidence, and therapeutic perspectives.Journal of natural medicines · 2026Review
- Analysis of the Efficacy of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease, Literature Review.International journal of molecular sciences · 2026Review
- Camphor Ameliorates Cadmium-induced Memory Deficits in Rats by Downregulating NF-κB and Enhancing Acetylcholine Signaling in the Hippocampus.Biological trace element research · 2026Article
- Why acetylcholinesterase inhibitors should be considered disease-modifying drugs for Alzheimer's disease?Aging clinical and experimental research · 2026Review
- Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives.Brain and behavior · 2026Article
- The complexity of dementia development and its comorbidities: The collaborative cross-mouse population for multivarious tasks approach.Animal models and experimental medicine · 2026Review
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Authors and funding
5 authors.
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Abstract
backgroundNeurodegenerative diseases (NDs) are conditions characterized by irreversible progressive degeneration to the nervous tissue and are usually associated with cognitive decline and functional deficits, especially in elderly. Acetylcholinesterase inhibitors (AChEIs) like donepezil, rivastigmine, and galantamine are commonly prescribed to alleviate cognitive symptoms associated with NDs. However, their long-term impact on slowing structural brain degeneration, particularly hippocampal atrophy, remains unclear.
objectiveThis systematic review and meta-analysis assess the efficacy of AChEIs in reducing hippocampal atrophy in patients with NDs or clinical syndromes that lead to cognitive decline.
methodsA systematic search of PubMed, Scopus, Web of Science, and Cochrane databases, since inception till 20th August 2024, identified randomized controlled trials (RCTs) and comparative studies that measured hippocampal volume changes in elderly patients with NDs and other clinical syndromes. Random effect model was employed to estimate the pooled atrophy rates. Subgroup analysis was conducted by disease, dosage, and side of the measurement.
resultsFrom 5,943 initially screened studies, nine were included in the review, and six were analyzed in the meta-analysis, encompassing a total of 2,179 participants. The meta-analysis showed that donepezil at a 10 mg dose significantly reduced hippocampal atrophy compared to placebo (SMD = 0.44, 95% CI [0.08 to 0.81], p = 0.01), whereas the 5 mg dose showed no significant effect on hippocampal volume. Overall, pooled results favored donepezil in reducing hippocampal atrophy (SMD = 0.33, p = 0.04), indicating that higher doses are more effective. Among patients with mild cognitive impairment (MCI), both donepezil and vitamin E were associated with a significant reduction in hippocampal atrophy compared to placebo (SMD = 0.27, p = 0.01). In contrast, galantamine did not significantly reduce hippocampal atrophy in the overall analysis, but it was associated with reduced whole brain atrophy in APOE ε4 carriers. Further analysis revealed no significant difference in the reduction of right or left hippocampal atrophy in donepezil-treated patients. These findings suggest that donepezil, particularly at higher doses, may have a protective effect against hippocampal atrophy in patients with AD and MCI, while galantamine's effect may be more limited, especially in certain genetic subgroups.
conclusionHigher doses of donepezil (10 mg) significantly reduce hippocampal atrophy in Alzheimer's disease and mild cognitive impairment, suggesting potential neuroprotective effects. In contrast, lower doses (5 mg) and galantamine showed no significant impact on hippocampal volume, though galantamine reduced whole brain atrophy in APOE ε4 carriers. Dosage and genetic factors are crucial in determining the efficacy of acetylcholinesterase inhibitors in slowing neurodegeneration.
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