Introduction: Treatment with antiparkinsonism anticholinergics (AAs) has been well-established for patients with Parkinson's disease (PD), especially for tremor. However, concerns regarding the association between anticholinergics and dementia risk are increasing. This retrospective cohort study investigated whether AAs increase the risk of dementia in patients with early-stage PD. Methods: Data were obtained from the National Health Insurance Research Database of Taiwan. In total, 30,740 patients with newly diagnosed PD were selected and matched based on the propensity score. Patients who were prescribed AAs within the first year of PD diagnosis were further categorized into two groups based on the exposure time, namely ≥6-month and <6-month exposure groups. Conditional Cox proportional regression analysis was used to examine dementia risk. Results: Exposure to AAs for ≥6 months conferred a significant increase in dementia risk (adjusted hazard ratio = 1.23, 95% confidence interval: 1.10–1.37). Subgroup analyses indicated that exposure to AAs for ≥6 months positively interacted with the conventional risk factors for dementia, such as age, hypertension, diabetes, and hyperlipidemia, resulting in greater risk of dementia in patients with early-stage PD. A class effect of AAs with other potent anticholinergics was demonstrated on dementia risk; co-exposure did not lead to a further increase in dementia risk. Conclusions: Greater exposure to AAs increased dementia risk in patients with early-stage PD, which was speculated to result from the class effect of anticholinergics. Although AAs have a therapeutic effect on patients with PD, it should be cautiously prescribed.
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