ADULTS receiving β3 adrenergic agonists for overactive bladder (OAB) did not have a lower incidence of dementia than those prescribed anticholinergic medications, according to a retrospective cohort study involving more than 830,000 patients. The findings challenge the assumption that β3 agonists offer a cognitive safety advantage over anticholinergic treatments.
The study compared dementia incidence across three medication groups: high-risk anticholinergics, low-risk anticholinergics, and β3 adrenergic agonists. Researchers also investigated whether longer exposure to anticholinergic medications was associated with an increased risk of dementia.
Researchers analysed electronic health record data from 830,393 adults aged 40–90 years who initiated pharmacological treatment for OAB between 2012 and 2025. Participants had no pre-existing dementia diagnosis and had started treatment within 1 year of their OAB diagnosis.
The cohort included 585,198 females (70.5%), with a median age of 67 years. Medications were categorised as high-risk anticholinergics (oxybutynin, tolterodine, or solifenacin), low-risk anticholinergics (darifenacin, trospium, or fesoterodine), or β3 agonists (mirabegron or vibegron).
Dementia incidence was identified through diagnostic codes or prescriptions for dementia-specific medication. Researchers used inverse probability of treatment weighting and Cox proportional hazards models to compare outcomes between medication groups.
During follow-up, 65,134 patients developed dementia. Following statistical adjustment, high-risk anticholinergics were associated with a lower dementia hazard than β3 agonists (hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.87–0.93).
High-risk anticholinergics also had a lower dementia hazard than low-risk anticholinergics (HR: 0.93; 95% CI: 0.90–0.96). However, no significant difference was identified between low-risk anticholinergics and β3 agonists (HR: 0.97; 95% CI: 0.93–1.01).
The weighted 10-year dementia risk was highest among β3 agonist users at 20.0%, compared with 18.1% among high-risk anticholinergic users.
Longer anticholinergic exposure was not associated with an increased incidence of dementia. However, researchers highlighted that the observed differences between medication groups were modest and potentially explained by residual confounding.
E-values of 1.29 and 1.20 indicated that relatively modest unmeasured confounding could account for the observed differences. Preferential prescribing of β3 agonists to patients perceived to be at greater cognitive risk was identified as one possible explanation.
Overall, the findings suggest that β3 agonists were not associated with lower dementia incidence than anticholinergic medications. The researchers concluded that previously reported associations between anticholinergic treatment and dementia may partly reflect residual confounding rather than a direct pharmacological effect.
Reference
Sheyn D et al. Drug therapies and incidence of dementia among adults with overactive bladder. JAMA Netw Open. 2026;9;(11):e2642026.
Featured image: pikselstock on Adobe Stock.
Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.
