Risks of Dementia Associated With Anticholinergic Medication Compared to Beta-3 Agonist Among Older Patients With Overactive Bladder in Japan: The LIFE Study

Objectives: Anticholinergic drugs can cause cognitive impairment. The risk of dementia associated with anticholinergics compared to beta-3 agonists (mirabegron and vibegron) has not been extensively investigated in the super-aging society of Japan. This study evaluated the association between the dementia risk and anticholinergics compared to beta-3 agonists in older adults with overactive bladder in Japan.

Methods: This study had 1,493,202 participants from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2022. The participants included 13,448 anticholinergic drug users and 24,669 beta-3 agonist users diagnosed with overactive bladder and aged ≥ 65 years. The Cox proportional hazards regression model was used to calculate hazard ratios and 95% confidence intervals being adjusted for confounding variables to evaluate the impact of anticholinergic drugs compared to beta-3 agonists prescribed at index date to patients with overactive bladder.

Results: Among the beta-3 agonist and anticholinergic drug users, the mean (standard deviation) age was 78.9 (6.7) and 78.8 (7.0) years, and the percentage of men was 47.2% and 39.7%, respectively. In the beta-3 agonist group, 2130 participants were newly diagnosed with dementia during the 51,605 person-years of follow-up from the index date, whereas in the anticholinergic drug group, 1826 participants were diagnosed during the 34,929 person-years of follow-up. In the Cox proportional hazard regression model, there was an increased risk of dementia in the anticholinergic drug group compared to the beta-3 agonist group (adjusted hazard ratio [aHR] = 1.22; 95% confidence interval [CI], 1.15-1.30). The increased risk remained identical when Inverse Probability Weighting (IPW) model was used for the analysis (aHR = 1.19; 95% CI, 1.11-1.28).

Conclusions: Compared to beta-3 agonists, anticholinergic drugs are associated with an increased risk of dementia in older adults with overactive bladder, in Japan. These findings suggest that beta-3 agonists may have a lower risk of dementia than anticholinergics and have potential to be a good alternative opinion for older people with OAB, which warrants further study.