Impact of Acetylcholinesterase Inhibitors on Movement Disorders

Background on Acetylcholinesterase Inhibitors and Alzheimer’s Disease

Acetylcholinesterase inhibitors (AChEIs) are a cornerstone in the pharmacological treatment of Alzheimer’s disease (AD), aimed at improving cognitive function by preventing the breakdown of acetylcholine, a neurotransmitter crucial for learning and memory. Approved AChEIs include donepezil, galantamine, rivastigmine, tacrine, and ipidacrine, with donepezil being one of the most commonly prescribed medications in the United States, ranking 131st among the top 300 prescribed medications in 2021 (Rissardo et al., 2025).

Despite their efficacy in symptom management, the use of AChEIs is not without risks. Recent systematic reviews have highlighted a range of adverse effects associated with these medications, particularly concerning movement disorders (MDs). The pharmacological mechanisms through which AChEIs operate can inadvertently impact the motor control pathways, leading to symptoms such as parkinsonism, myoclonus, dystonia, and tremors, particularly in the elderly population who are already at risk for these conditions due to age-related neurodegeneration (Rissardo et al., 2025).

Common Movement Disorders Associated with AChEIs

The adverse events related to AChEIs encompass a spectrum of movement disorders. According to a systematic review conducted by Rissardo et al. (2025), the most frequently reported AChEI-induced movement disorders included:

• Pisa Syndrome: Characterized by an abnormal posture, where patients lean to one side, occurring in 33 identified cases.
• Parkinsonism: Symptoms resembling Parkinson’s disease, reported in 31 cases.
• Myoclonus: Sudden, involuntary muscle jerks observed in 11 cases.
• Dystonia: Sustained muscle contractions and abnormal postures noted in 10 cases.
• Dyskinesia: Involuntary movements, reported in 6 cases.
• Extrapyramidal Symptoms: Generalized movement disorders, observed in 1 case.

These movement disorders were predominantly associated with donepezil (62 cases), followed by rivastigmine (15 cases), galantamine (10 cases), and tacrine (5 cases), while no cases were linked to ipidacrine (Rissardo et al., 2025).

Methodology for Assessing AChEI-Induced Movement Disorders

To evaluate the impact of AChEIs on movement disorders, a comprehensive systematic review was conducted, encompassing studies published from 1992 to 2024 across multiple databases, including PubMed and ScienceDirect. The researchers focused on case reports, clinical trials, and cohort studies that documented instances of movement disorders attributed to AChEIs. The assessment criteria included:

• Demographic Characteristics: Age, sex, and underlying health conditions of the patients.
• Onset Timing: The time frame from the initiation of AChEI therapy to the appearance of movement disorders.
• Recovery Outcomes: The effectiveness of interventions, including AChEI discontinuation and alternative treatments, on the resolution of movement disorders.

The review synthesized data from 74 studies, involving a total of 92 cases, to establish a clear connection between AChEI use and the onset of movement disorders in patients diagnosed with Alzheimer’s disease (Rissardo et al., 2025).

Key Findings: Prevalence and Types of Movement Disorders

The findings from the systematic review conducted by Rissardo et al. (2025) revealed that approximately 70% of patients experienced movement disorders within the first six months of initiating AChEI therapy. The mean age of affected individuals was 74.1 years, with a higher prevalence among females (61.9%). Notably, the majority of movement disorders were reversible upon modification of treatment, with approximately 86.3% of patients achieving full recovery after management interventions, which often included dose adjustments and the cessation of AChEIs.

Table 1: Summary of Movement Disorders Associated with AChEIs

Management and Recovery from AChEI-Induced Movement Disorders

Managing AChEI-induced movement disorders primarily focuses on identifying symptoms early and adjusting treatment regimens accordingly. The protocols typically involve:

1. Discontinuation of AChEIs: This is often the first step in managing drug-induced movement disorders.
2. Symptomatic Treatment: In cases where discontinuation is not feasible, adjunctive therapy with medications such as anticholinergics may be considered.
3. Patient Monitoring: Regular follow-ups to assess the progression or resolution of movement disorders are crucial.
4. Physical Therapy: Engaging patients in physical therapy can help mitigate the effects of movement disorders and improve overall mobility.

Recovery from AChEI-induced movement disorders is generally favorable, with most patients experiencing significant improvement within six months of intervention. Rissardo et al. (2025) report that about 80% of patients fully recover after appropriate management strategies are employed.

FAQ Section

What are Acetylcholinesterase inhibitors (AChEIs)?

AChEIs are medications used primarily to treat Alzheimer’s disease by inhibiting the enzyme acetylcholinesterase, thereby increasing levels of acetylcholine in the brain.

What types of movement disorders are associated with AChEIs?

Common movement disorders associated with AChEIs include Pisa syndrome, parkinsonism, myoclonus, dystonia, dyskinesia, and extrapyramidal symptoms.

How prevalent are movement disorders in patients taking AChEIs?

Approximately 70% of patients may develop movement disorders within the first six months of starting AChEI therapy, with a higher incidence in older adults.

What management strategies are effective for AChEI-induced movement disorders?

Management strategies include discontinuation of AChEIs, symptomatic treatment, physical therapy, and regular monitoring of symptoms.

What is the prognosis for recovery from AChEI-induced movement disorders?

The prognosis for recovery is generally positive, with around 80% of patients experiencing full recovery following treatment adjustments.

References

1. Rissardo, J. P., Caprara, A. L., & Fornari, A. L. (2025). Movement disorders associated with acetylcholinesterase inhibitors in Alzheimer’s dementia: A systematic review. Brain Circulation. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11984823/