Large bladder-drug study finds no dementia advantage for beta-3 agonists over anticholinergics

Researchers used Epic Cosmos electronic health records from 2012 to 2025 to follow adults aged 40 to 90 who were newly treated for overactive bladder and had no dementia at the start. They compared three groups by first prescription: high-risk anticholinergics (oxybutynin, tolterodine or solifenacin), lower-risk anticholinergics (darifenacin, trospium or fesoterodine) and beta-3 agonists (mirabegron or vibegron).

What they found

Among 830,393 patients (median age 67), 65,134 developed dementia. After inverse probability weighting, high-risk anticholinergics were associated with a lower hazard of dementia than beta-3 agonists (HR 0.90, 95% CI 0.87 to 0.93). Lower-risk anticholinergics did not differ from beta-3 agonists (HR 0.97, 95% CI 0.93 to 1.01). Longer anticholinergic use was not associated with higher risk.

The nuance

This does not show that anticholinergics protect the brain. The authors’ E-values (1.29 and 1.20) indicate that a modest amount of unmeasured confounding could explain the differences, and follow-up was shorter for beta-3 agonists. Anticholinergic drugs can still cause confusion, constipation and dry mouth in older adults, and geriatric prescribing guidance continues to urge caution.

Youthful take

Do not stop or switch a bladder medication on your own. Bring this question to your physician, who can review your full medication list, your cognitive health and your goals.