Clinical Report: Putting Unexpected Safety Findings for OAB Treatments in Context

Overview

In a retrospective cohort of 830,393 adults treated for overactive bladder (OAB), β3 adrenergic agonist exposure was not associated with a statistically significant reduction in incident dementia compared with anticholinergic exposure. The authors caution that confounding and other observational-study limitations may explain the findings; they also note that concern about potential adverse effects of strongly anticholinergic medications supports considering alternative therapies.

Background

OAB is treated with anticholinergic medications and β3 adrenergic agonists, while concern about anticholinergic effects on cognition has grown from the cholinergic hypothesis and observational associations between anticholinergic exposure and dementia. This concern has contributed to changes in prescribing, although the source notes that evidence supporting the shift to β3 agonists had been limited. The study by Sheyn et al examined dementia incidence after initiation of OAB treatments using electronic health record data. Its findings differ from those of earlier investigations, and the authors identify potential confounding as an important interpretive limitation.

Data Highlights

Key Findings

• Sheyn et al analyzed 830,393 adults aged 40 to 90 years who initiated OAB treatment within 1 year of diagnosis and had no preexisting dementia.
• Dementia was identified using administrative diagnosis codes or prescriptions for dementia-related medications.
• After adjustment using inverse probability of treatment weighting, β3 agonist exposure was not associated with a statistically significant lower dementia incidence than anticholinergic exposure.
• Following confounder balancing, regular anticholinergic use was associated with a modestly lower hazard, while β3 agonists showed the highest 10-year incidence.
• The exploratory duration-response analysis found no association between longer anticholinergic exposure and increased dementia risk.
• The authors note that channeling bias, residual confounding, and confounding by indication—including the possibility that OAB may precede neurodegenerative or cerebrovascular processes—could account for the observed associations.

Clinical Implications

The study does not establish that β3 agonists prevent dementia or that anticholinergic medications reduce dementia risk; its retrospective design and potential confounding limit causal interpretation. The source states that, pending prospective studies with rigorous dementia definitions, concern about potential adverse effects of strongly anticholinergic medications makes alternative therapies, including β3 agonists, a reasonable option.

Conclusion

In this large retrospective cohort, β3 agonists were not associated with lower dementia incidence than anticholinergic medications. The authors call for further prospective evidence and continued development of treatments that are safe and effective for OAB and Alzheimer disease and related dementias.

Related Resources & Content

1. Sheyn et al, JAMA Network Open, 2026 -- Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder
2. European Association of Urology, EAU Guidelines on Non-neurogenic Female LUTS, 2026 -- Summary of changes
3. MDSpire News, year not stated -- Researchers Question Routine Urodynamic Testing
4. Journal of Medical Internet Research, 2026 -- Impact of Digital Health Interventions on Symptom Relief and Quality of Life in Individuals with Overactive Bladder: A Systematic Review and Meta-Analysis
5. JMIR Medical Informatics, 2026 -- A Predictive Model Utilizing Machine Learning to Assess Overactive Bladder Risk in Women in the United States: Insights from the National Health and Nutrition Examination Survey 2011-2018
6. ASCO Publications — Radical Treatment of the Primary Tumor in Metastatic Bladder Cancer: Potentially Dangerous Findings From Observational Data
7. Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder
8. EAU Guidelines on Non-neurogenic Female LUTS - Summary of changes
9. IncobotulinumtoxinA Versus OnabotulinumtoxinA for Treatment of Overactive Bladder Syndrome: A Randomized Single-blinded Non-inferiority Trial.