Are newer OAB drugs really safer for cognition?

Clinical takeaway: When selecting pharmacologic therapy for overactive bladder (OAB), do not assume that β3 agonists offer a lower risk of dementia than anticholinergic agents. In this large real-world study, dementia incidence was similar across drug classes, and longer anticholinergic use was not associated with increased risk.

Concerns that anticholinergic medications may contribute to dementia have led many clinicians to view β3 agonists as the cognitively safer option for OAB. This study sought to determine whether real-world dementia outcomes support that assumption.

Contrary to expectations, β3 agonists were not associated with lower dementia incidence. After adjustment for demographic and clinical differences, patients prescribed high-risk anticholinergics had a roughly 10% lower likelihood of developing dementia than those receiving β3 agonists, while dementia risk was similar between β3 agonists and low-risk anticholinergics. Weighted 10-year dementia risk estimates were 20.0% for β3 agonists, 19.0% for low-risk anticholinergics, and 18.1% for high-risk anticholinergics.

In this retrospective cohort study, investigators analyzed electronic health record data from 830,393 adults aged 40 to 90 years (70 % female, median age 67 years[SC1] ) with OAB who initiated treatment with either a β3 agonist, a high-risk or a low-risk anticholinergic (based on blood brain barrier penetration). Overall, 65,134 patients developed dementia during follow-up.

Importantly, analyses examining treatment duration found no evidence that longer anticholinergic exposure increased dementia risk. The investigators suggest the modest differences observed between drug classes may reflect residual channeling bias rather than a true pharmacologic effect, noting that clinicians often follow guideline recommendations to preferentially prescribe β3 agonists to patients perceived to be at higher risk for cognitive decline.

Source Sheyn D, et al. (2026 Nov 6) JAMA Network Open. Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder