The use of specific anticholinergic medications for overactive bladder has been associated with an increased risk of dementia, according to a nested case-control study published in BMJ Medicine. The study analyzed data from England’s Clinical Practice Research Datalink, including 170,742 patients with dementia and 804,385 matched controls aged 55 years and older.

The study found that cumulative use of certain anticholinergics, including oxybutynin hydrochloride, solifenacin succinate, and tolterodine tartrate, was associated with a higher dementia risk. Patients taking oxybutynin for more than three years at standard doses had an adjusted odds ratio (OR) of 1.31. Solifenacin and tolterodine showed similar risks, with ORs of 1.29 and 1.25, respectively. The overall adjusted OR for any anticholinergic use for OAB was 1.18.

In contrast, no significant increase in dementia risk was observed for darifenacin, fesoterodine fumarate, or trospium chloride. Mirabegron, a non-anticholinergic β3-adrenoceptor agonist, demonstrated variable associations that may have been influenced by prior use of anticholinergic medications in the study population.

The findings also suggested a stronger association in men compared to women. The median age of participants was 83 years, and 62.6% were women.

The study accounted for potential confounding factors, including comorbidities, sociodemographic variables, and use of other anticholinergic medications. A three-year exclusion period prior to dementia diagnosis was applied to minimize protopathic bias. Researchers attributed the increased risk of dementia to the ability of lipophilic anticholinergic drugs, such as oxybutynin, to cross the blood-brain barrier and interact with central muscarinic receptors.

The authors noted that cumulative use exceeding 1,095 days represents approximately three years of daily use at standard doses and emphasized the importance of considering alternative treatments. Full study disclosures and limitations are available in the published article.