The use of anticholinergic bladder drugs was associated with a 44% increased risk of dementia compared with nonuse, but no increased risk was observed when compared with the beta-3 agonist mirabegron, according to a recent study.
Researchers conducted a nationwide nested case-control study in Denmark, analyzing data from 2.26 million participants to examine the association between cumulative use of anticholinergic bladder drugs and the risk of all-cause dementia. The study investigators—who published their findings in BMJ Medicine—utilized Danish national registry data from January 2000 to December 2022. They evaluated two cohorts: a general population cohort of 2.26 million participants aged 60 to 75 years with no prior dementia, and a secondary cohort of 58,242 new users of bladder drugs. The primary analysis compared the use of anticholinergic bladder drugs with nonuse, while the secondary analysis utilized mirabegron as an active comparator.
Researchers identified 129,254 participants diagnosed with dementia and matched them by age and sex to 646,270 controls. In the secondary cohort, 2,198 participants with dementia were matched to 10,990 controls. Medication use was determined through filled prescriptions and defined daily doses (DDDs). Conditional logistic regression models were employed to estimate adjusted incidence rate ratios (IRRs) for dementia risk, controlling for educational level, cardiovascular disease, diabetes, hypertension, dyslipidemia, and the Charlson Comorbidity Index.
Results demonstrated that ever-use of anticholinergic bladder drugs was associated with a significantly increased risk of dementia compared with nonuse (IRR = 1.44; 95% confidence interval [CI] = 1.40–1.48). A dose-response relationship was observed, with an IRR of 1.31 (95% CI = 1.27–1.36) for 1 to 90 DDDs and an IRR of 1.68 (95% CI = 1.59–1.76) for more than 365 DDDs. Specifically, tolterodine (IRR = 1.43; 95% CI = 1.38–1.49), solifenacin (IRR = 1.37; 95% CI = 1.29–1.46), trospium (IRR = 1.52; 95% CI, 1.37–1.67), and fesoterodine (IRR = 1.48; 95% CI, 1.26–1.74) were all associated with increased dementia risk.
When using mirabegron as an active comparator, no increased risk of dementia was observed with anticholinergic bladder drugs (IRR = 0.82; 95% CI = 0.74-0.92). The study used an active comparator to address potential biases present in prior observational research. Sensitivity analyses incorporating a 2-year lag period yielded similar results.
The researchers—led by Nelsan Pourhadi, MD, of the Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet—noted that prior studies linking anticholinergic bladder drugs to dementia risk may have been influenced by confounding factors such as protopathic bias and indication bias. They emphasized the value of active comparators in observational studies assessing the cognitive risks of pharmacologic treatments for overactive bladder, and suggested that further investigation is needed to evaluate the long-term cognitive effects of both anticholinergic bladder drugs and beta-3 agonists.
Full disclosures can be found in the published study.