The Impact of Anticholinergic Use for Overactive Bladder on Cognitive Changes in Adults with Normal Cognition, Mild Cognitive Impairment, or Dementia

Background: Few studies have addressed whether anticholinergic (AC) medications for overactive bladder (OAB) cause cognitive decline in individuals with existing cognitive impairment, and whether the ε4 gene increases this risk.

Objective: To determine whether OAB AC use is associated with a clinically relevant change in cognitive measures among adults with normal and abnormal cognition.

Design Setting And Participants: This was a retrospective cohort study using data from the National Alzheimer's Coordinating Center. Patients were enrolled at specialized centers in the USA between 2005 and 2019. Patients with existing OAB AC use, missing ε4 status, and confounding neurologic diagnoses were excluded. New users of an OAB AC were matched 1:1 to patients not taking an OAB AC using propensity scores.

Intervention: New use of oxybutynin, tolterodine, solifenacin, trospium, darifenacin, or fesoterodine.

Outcome Measurements And Statistical Analysis: The outcome was a change in cognitive function, measured as a ≥1-point increase on the Clinical Dementia Rating (CDR) instrument or a ≥3-point decrease on the Mini-Mental State Examination (MMSE). Conditional logistic regression with odds ratios (ORs) was conducted. We also tested for ε4 effect modification.

Results And Limitations: Among 18 835 eligible patients, 782 matched pairs were identified. The most common OAB ACs were oxybutynin (38%) and tolterodine (23%). There was no significant increase in the risk of a clinically relevant cognitive decline among OAB AC users (CDR: OR 1.38, 95% confidence interval [CI] 0.93-2.05;  = 0.11, MMSE: OR 1.06, 95% CI 0.79-1.43;  = 0.70). There was no significant interaction between ε4 status and OAB AC use for the CDR ( = 0.38) or MMSE ( = 0.95) outcomes. Users of oxybutynin or tolterodine had numerically higher odds of a change on the CDR test (OR 1.65, 95% CI 0.98-2.77) that was close to statistical significance ( = 0.06). Limitations include the inability to determine medication dose or duration, and residual confounding.

Conclusions: OAB AC use was not associated with a significant change in cognitive function among individuals with normal and abnormal cognition. Further research is necessary to determine if oxybutynin and tolterodine are significantly more likely to cause cognitive decline.

Patient Summary: Use of a specific class of overactive bladder medication was not associated with negative changes in brain function among patients with either normal or abnormal function. A genetic risk factor for Alzheimer's disease did not predispose individuals to cognitive decline when taking these drugs. Two of the drugs (oxybutynin and tolterodine) may lead to a higher risk of cognitive decline in comparison to other drugs, and this needs further research.