To the Editor In their recent study, Coupland et al1 conclude that, at sufficiently high dosages, exposure to 11 disparate anticholinergic drug classes is associated with increases in observed dementia. They focus on 4 drug classes as particularly concerning: antidepressants, bladder antimuscarinic drugs, antiparkinson drugs, and epilepsy drugs.
However, because they excluded everyone with a diagnosis of Parkinson disease from both their case patients and controls to help address indication bias, their data cannot apply to patients with Parkinson disease. Furthermore, Table 51 shows that the exclusion of patients with Parkinson disease resulted in 99.5% and 99.8% of their case patients and controls, respectively, never having used antiparkinson drugs. This extreme sparseness undoubtedly led to the lack of statistical significance in 2 of 4 dosage groups and to an extremely nonmonotonic dose effect. Although a small number of patients without Parkinson disease may have taken antiparkinson medications for other medically supportable reasons, it is critical to have a clear caveat that the results do not necessarily apply to patients with Parkinson disease. Similarly, although patients with epilepsy were not apparently excluded from the study, 97.6% and 98.0% of the case patients and controls, respectively, had never taken antiepileptic drugs, which was likely the cause of the lack of statistical significance in 3 of 4 dosage categories (Table 51).
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Paul LM. Association of Anticholinergic Drug Exposure With Increased Occurrence of Dementia. JAMA Intern Med. 2019;179(12):1729. doi:10.1001/jamainternmed.2019.4905
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