Article type: Literature Review
Article title: Movement disorders associated with acetylcholinesterase inhibitors in Alzheimer’s dementia: A systematic review
Journal: Brain Circulation
Year: 2025
Authors: Jamir Pitton Rissardo and Ana Letícia Fornari Caprara
E-mail: jamirrissardo@gmail.com
ABSTRACT
Background: Acetylcholinesterase inhibitors (AChEIs) are widely used in Alzheimer’s disease (AD). This study aims to systematically review the literature about movement disorders (MDs) associated with AChEIs for AD, which include donepezil, galantamine, rivastigmine, tacrine, and ipidacrine. Methodology: Two reviewers conducted a comprehensive review of relevant studies across six databases, without language restrictions, covering publications from 1992 to 2024. Results: Overall, 74 studies containing 92 cases were found of MDs related to ACHEIs. The MDs found were Pisa syndrome in 33 patients, parkinsonism in 31, myoclonus in 11, dystonia in 10, dyskinesia in 6, and extrapyramidal symptoms in 1. Regarding the medications, the abnormal movements were associated with donepezil in 62 cases, rivastigmine in 15, galantamine in 10, and tacrine in 5. No case of ipidacrine-induced MD was found. Overall, the most commonly affected sex was the female, accounting for 61.9% of the cases. The mean and median age was 74.1 (standard deviation: 8.9) and 75 years (range: 49–93 years). The MD occurred within 6 months of the starting of AChEI in approximately 70% of the patients. Furthermore, the full recovery of the MD after the main management was noticed within 6 months in about 80% of the patients. About 86.3% of the individuals fully recovered after treatment, which included AChEI discontinuation, dose adjustment, and prescription of additional therapy. Conclusions: The occurrence of tacrine-induced tremor indicated a potential predisposition to movement disorders associated with AChEI therapy. Based on the drug class side effect profile, it is possible that future studies may observe abnormal movements with other AChEIs.
Keywords: Adverse effect, donepezil, drug‑induced, extrapyramidal symptom, galantamine, movement disorder, rivastigmine.
Full text available at:
DOI
Citation
Rissardo JP, Caprara AL. Movement disorders associated with acetylcholinesterase inhibitors in Alzheimer’s dementia: A systematic review. Brain Circ 2025;11:9-23.
Figure 1. Flowchart of the screening process.
Figure 2. Movement disorder onset. The figure describes the percentage of individuals with Acetylcholinesterase inhibitor (AChEI)‑associated movement disorder versus the time between the AChEI’s start and the movement disorder’s development in weeks.
Figure 3. Movement disorder recovery. The figure describes the percentage of individuals with Acetylcholinesterase inhibitor‑associated movement disorder that fully recovered versus the time between the management and the full recovery.
Table 1. Summary of acetylcholinesterase inhibitor‑associated movement disorder.
Table 2. Abnormal movement percentages reported in clinical trials with acetylcholinesterase inhibitors.
Supplementary Table 1. Acetylcholinesterase inhibitors used for Alzheimer’s disease therapy.
Supplementary Table 2. FreeText and MeSH search terms in the US National Library of Medicine.
Supplementary Table 3. Preferred reporting items for systematic reviews and meta‑analyses 2020 checklist.
Supplementary Table 4. Literature review of movement disorders associated with donepezil, galantamine, rivastigmine, tacrine, and ipidacrine.
Supplementary Table 5. Tacrine‑induced tremulous jaw movements rat model studies in PubMed.