Mirabegron and Memory: The Twelve-Week Trial and Longer Dementia Studies

Mirabegron is a beta-3 agonist used for overactive bladder, a different drug class from antimuscarinic medicines such as oxybutynin.¹ That distinction often enters discussions about memory. The evidence needs a second distinction: a cognitive test after twelve weeks and a dementia diagnosis years later are different outcomes.

What PILLAR measured

The randomized PILLAR trial included 887 treated adults aged 65 or older with overactive bladder and urgency leakage. 836 had paired Montreal Cognitive Assessment (MoCA) scores. This is a 30-point screening instrument; the trial compared mirabegron with placebo over twelve weeks.²

Adjusted average score changes were −0.2 points with mirabegron and −0.1 with placebo, with no statistically detectable between-group difference (P=0.471).²

Participants were generally healthy, community-dwelling older adults. The study was powered for bladder outcomes, not a difference in MoCA scores. Astellas initiated and funded it and contributed to design, analysis and interpretation. The finding cannot establish years of dementia safety or describe every frail older patient.²

Why the prescription studies require different questions

The 2024 English study³ compared 170,742 people with dementia with 804,385 matched controls, examining bladder-drug prescriptions three to sixteen years before diagnosis. Any bladder anticholinergic use was associated with an adjusted odds ratio of 1.18 relative to non-use. That does not mean an individual has an 18% probability of dementia.³

Mirabegron results were difficult to interpret: 86.2% of its users had previously used anticholinergic bladder drugs. Their later diagnoses cannot neatly be assigned to one medicine. These were prescribing records, not randomly allocated treatments.³

The 2025 Danish study⁴ illustrates how the comparison group can change the result. Anticholinergic bladder drugs were associated with a higher dementia rate than non-use: adjusted incidence rate ratio 1.44. But a separate analysis of 58,242 new bladder-drug users compared anticholinergics with mirabegron. The ratio was 0.82 (95% confidence interval 0.74–0.92), favoring anticholinergics in that analysis.⁴

This does not demonstrate that anticholinergics protect memory or that mirabegron causes dementia. The authors discuss differences in underlying bladder symptoms and prescribing choices: clinicians might select mirabegron for people whose cognitive vulnerability is not fully captured in the records. Statistical adjustment cannot remove every such difference.⁴

Nor do all comparisons between drug classes agree. The 2025 Japanese LIFE study⁵ included 13,448 anticholinergic users and 24,669 beta-3 agonist users aged 65 or older. Its adjusted dementia hazard ratio was 1.22 (95% confidence interval 1.15–1.30) for anticholinergics versus beta-3 agonists. The comparator combined mirabegron and vibegron, so this is not a mirabegron-only estimate. It was also observational.⁵

The practical reading is to keep the population, previous exposure, comparator and outcome beside each number. A screening-score result cannot settle dementia incidence, and an association in medical records cannot establish which drug caused a diagnosis.

What belongs in the prescribing conversation

Statement 18 of the US 2024 AUA/SUFU guideline calls for discussing potential dementia and cognitive-impairment risk when prescribing antimuscarinic OAB medicines. That guideline predates the two 2025 studies above; the discussion remains appropriate without treating their conflicting results as a settled causal verdict.⁶

Bring the names of current and previous bladder medicines, approximate treatment dates and any cognitive changes you have noticed. Useful questions include:

• What bladder benefit would justify continuing this medicine?
• Do my other medicines affect this choice?
• What should prompt a call or an earlier review?

The US mirabegron label includes postmarketing reports of confusion and hallucinations, while stating that a causal relationship has not been established. Voluntary reports cannot supply a reliable frequency. Its blood-pressure, urinary-retention and interaction precautions also still apply.¹ Our beta-3 medicine appointment guide covers those checks.

Chapter 9’s “The Next Rungs” in Laugh, Sneeze, Jump places medicines within the wider bladder treatment discussion. Use that discussion to agree on the benefit you are tracking and a review date, rather than choosing a prescription from one reassuring study headline.