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Increased risk of dementia among overactive bladder patients treated with an anticholinergic medication compared to a beta-3 agonist: a population-based cohort study

Welk B, McArthur E. BJU Int. 2020; Mar 12 [Epub ahead of print]. DOI:

Objective — To determine if there is an increased risk of dementia among overactive bladder patients starting anticholinergic medication compared to those starting a beta-3 agonist.

Methods — We conducted a population-based, retrospective, matched cohort study using linked administrative data from Ontario, Canada from 2010-2018. We matched 47,324 new users of anticholinergic medications (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, trospium) to 23,662 new users of a beta-3 agonist medication (mirabegron); all of the included medications are only indicated for the treatment of overactive bladder. We measured 75 baseline variables (including comorbid conditions, recent medications, and prior healthcare utilization) and used these to create a propensity score; groups were similar across all measured variables after matching. The primary exposure was the class of overactive bladder medication (anticholinergic or beta-3 agonist). The primary outcome was dementia using a validated administrative data definition. 

Results — The most common anticholinergics used were tolterodine (40%), oxybutynin (29%) and solifenacin (26%). The median prescription duration among anticholinergics was 30 (IQR 30-170) days. The median prescription duration of a beta-3 agonist (mirabegron) was 64 (IQR 30-317) days. There was an increased risk of dementia among anticholinergic users compared to beta-3 agonist users (HR 1.23, 95% CI 1.12-1.35). There was significant effect modification based on both gender and age; men and those ≤75 years of age on anticholinergics had the highest risk of dementia relative to similar beta-3 agonist users.

Conclusions — The use of anticholinergic medications among overactive bladder patients was associated with an increased risk of new onset dementia compared to beta-3 agonist users. These results address the potential protopathic bias present in other studies, and support the association between the anticholinergic medication use and dementia.