OAB Cohort Finds No Lower Dementia Incidence With β3 Agonists

A retrospective cohort study of 830,393 adults treated for overactive bladder found no lower incidence of dementia among patients initiating β3 agonists than among those starting anticholinergics. The authors caution that modest unmeasured confounding could explain the observed differences.

Cohort included 830,393 adults treated for overactive bladder.
β3 agonists were not associated with lower dementia incidence.
Longer anticholinergic duration was not linked to increased risk.
Residual confounding limits causal interpretation.

Researchers used Epic Cosmos electronic health record data from 2012 to 2025 to compare incident dementia among adults aged 40 to 90 years newly treated for overactive bladder. The retrospective cohort included 830,393 patients without preexisting dementia. Initial therapies were classified as high-risk anticholinergics, low-risk anticholinergics, or β3 agonists; dementia was identified through diagnosis codes or dementia-specific medication use. Analyses used inverse probability of treatment weighting and Cox models.

Dementia was identified in 65,134 patients. After weighting, high-risk anticholinergics were associated with a lower dementia hazard than β3 agonists (hazard ratio, 0.90; 95% CI, 0.87-0.93) and low-risk anticholinergics (HR, 0.93; 95% CI, 0.90-0.96). Low-risk anticholinergics and β3 agonists did not differ significantly (HR, 0.97; 95% CI, 0.93-1.01). Weighted 10-year dementia risk was 20.0% with β3 agonists and 18.1% with high-risk anticholinergics. Longer anticholinergic use was not associated with increased risk.

The findings do not support the assumption that β3 agonists were associated with lower dementia incidence in this cohort. The retrospective design cannot establish causation, and the authors’ E-value analysis indicated that modest unmeasured confounding could explain observed differences. The results do not establish that anticholinergics protect against dementia.

In practice

For adults treated for overactive bladder, this large retrospective cohort found no lower dementia incidence with β3 agonists than with anticholinergics, and longer anticholinergic duration was not associated with increased risk. These findings challenge the presumption that β3 agonists are cognitively safer in this population, but they do not establish that anticholinergics reduce dementia risk or support changing treatment choices. The observational design and E-values indicate that modest unmeasured confounding could explain the differences; treatment effects remain uncertain.

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Source

JAMA Network Open: Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder ↗

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