Among patients with overactive bladder (OAB), anticholinergic medication use appears to be associated with an increased risk of new onset dementia when compared with beta-3 agonist use, according to the findings of a retrospective population-based cohort study.  

The study utilized linked administrative data from Ontario, Canada, to determine whether OAB patients initiating an anticholinergic medication had an increased risk of dementia compared with those initiating a beta-3 agonist. A group of new users of anticholinergic medications (n=47,324) used to treat OAB (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, and trospium) were matched to new users of the beta-3 agonist medication, mirabegron (n=23,662). After matching, the groups were similar across all 75 measured baseline variables (ie, comorbid conditions, recent medication use, and past healthcare utilization). The primary outcome of the analysis was dementia.

Findings of the study revealed tolterodine, oxybutynin, and solifenacin to be the most common anticholinergic medications used (40%, 29%, and 26%, respectively). The median prescription duration was found to be 30 days (interquartile range [IQR], 30-170) for anticholinergic medications compared with 64 days (IQR, 30-317) for mirabegron. 

The study authors reported that users of anticholinergic medications were found to have an increased risk of new onset dementia compared with beta-3 agonist users (hazard ratio [HR] 1.23; 95% CI, 1.12-1.35). “Anticholinergics may affect cognitive function by increasing amyloid plaques, or by directly inhibiting specific muscarinic receptors in the prefrontal cortex and hippocampus,” the authors hypothesized.

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Findings of the analysis also revealed 2 significant effect modifiers: gender and age. Males and patients ≤75 years old using anticholinergic medications were found to have the highest risk of dementia compared to similar users of beta-3 agonists. The authors noted that this effect had not been observed in past research of this area. “The higher magnitude of relative risk among people ≤75 years of age may be due to a time specific period in which a patients’ progression from mild cognitive impairment to dementia can be accelerated by anticholinergic medications,” they stated.

According to the findings of this cohort study, use of OAB anticholinergic medications may be associated with an increased risk of new onset dementia. The authors concluded, “Further research should be carried out to explore the identified effect modifiers of gender and age in this patient population, and to assess the differential effects of specific OAB anticholinergics.”

Reference

Welk, B. and McArthur, E. (2020), Increased risk of dementia among patients with overactive bladder treated with an anticholinergic medication compared to a beta‐3 agonist: a population‐based cohort study. BJU Int. doi:10.1111/bju.15040