Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder

Importance: Concern that anticholinergic medications for overactive bladder (OAB) are associated with increased dementia risk has encouraged a shift toward β3 adrenergic agonists, which are presumed cognitively safer. Whether this presumption is justified is uncertain. Objective: To compare the risk of incident dementia among adults initiating high-risk anticholinergic, low-risk anticholinergic, or β3 agonist therapy for OAB and to evaluate the association of treatment duration with risk. Design, Setting, and Participants: This retrospective cohort study used Epic Cosmos electronic health record data from 2012 to 2025. Adults aged 40 to 90 years newly treated for OAB within 1 year of diagnosis without preexisting dementia were included. Exposures: First prescribed medication class: high-risk anticholinergics (oxybutynin, tolterodine, or solifenacin), low-risk anticholinergics (darifenacin, trospium, or fesoterodine), or β3 agonists (mirabegron or vibegron). Main Outcomes and Measures: Incident dementia by diagnosis code or dementia-specific medication. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards models were used, with analyses stratified by age and sex and an exploratory landmark duration-response analysis. Results: Among 830 393 patients (585 198 female [70.5%]; median [IQR] age, 67 [57-76] years), incident dementia occurred in 65 134 patients, with a median (IQR) follow-up ranging from 1046 (571-1809) days for β3 agonists to 1568 (857-2614) days for high-risk anticholinergics. After IPTW, high-risk anticholinergics were associated with a lower hazard of dementia than β3 agonists (hazard ratio [HR], 0.90; 95% CI, 0.87-0.93) and low-risk anticholinergics (HR, 0.93; 95% CI, 0.90-0.96); low-risk anticholinergics did not differ from β3 agonists (HR, 0.97; 95% CI, 0.93-1.01). Weighted 10-year dementia risk was highest for β3 agonists (20.0%; 95% CI, 18.8%-21.2%) and lowest for high-risk anticholinergics (18.1%; 95% CI, 17.9%-18.3%). E-values of 1.29 (high-risk anticholinergics vs β3 agonists) and 1.20 (high-risk vs low-risk anticholinergics) suggested that observed differences could be explained by a modest amount of unmeasured confounding. Longer anticholinergic duration was not associated with increased risk. Conclusions and Relevance: In this cohort study of patients undergoing treatment for OAB, β3 agonists were not associated with a lower dementia incidence compared with anticholinergics. These findings suggest that previously reported increases in risk may reflect residual confounding rather than a pharmacological effect.