A Double-blind, Randomised Four-way Crossover Study to Compare the Effects of Fesoterodine 4 and 8 mg Once Daily and Qxybutynin 5 mg Twice Daily After Steady-state Dosing Versus Placebo on Cognitive Function in Overactive Bladder-wet Patients over the Age of 75 Years with Mild Cognitive Impairment.

ABSTRACT

BACKGROUND AND OBJECTIVE: There is a reported association between overactive bladder (OAB) treated with antimuscarinic drugs and an increased risk of a dementia diagnosis, although short-term data suggest that newer OAB antimuscarinics are cognitively safe. This study examined the cognitive safety of fesoterodine in older adults with mild cognitive impairment (MCI) and OAB. METHODS: This four-way randomised crossover study examined the cognitive effects of fesoterodine 4 and 8 mg and oxybutynin 5 mg b.i.d. compared with placebo. Older adult patients with OAB and MCI were included. Treatment and washout periods were of 1-week duration, to reach steady-state drug levels. The primary outcome was continuity of attention at 1 and 4 h after the dose. The secondary outcomes included other cognitive domains, change in Montreal Cognitive Assessment score, and alertness. KEY FINDINGS AND LIMITATIONS: Twenty-three patients completed the study (16 females and seven males). For the primary outcome, at 1 h after the dose, a trend towards worsening of continuity of attention was observed for fesoterodine 4 mg (p = 0.09) compared with placebo. At 4 h after the dose, a nonstatistically significant trend towards improvement compared with placebo was observed in the fesoterodine 4 mg group (p = 0.0633) compared with placebo. No differences were observed in any other treatment group at either time point. Apart from quality of working memory, associated with a statistically significant improvement with fesoterodine 4 mg, there was no difference in any comparison for other secondary outcomes. CONCLUSIONS: Exposure to steady-state dosing of fesoterodine 4 and 8 mg or oxybutynin 5 mg b.i.d. was not associated with any detectable effect on cognitive function using a sensitive battery of cognitive tests in a group of older adult patients with MCI and OAB. PATIENT SUMMARY: In this report, we investigated whether the medication fesoterodine, a member of a family of drugs called anticholinergics, commonly used for the treatment of a condition called overactive bladder that leads to accidental leakage of urine, affected the memory function of older adults with mild memory impairment. These people might be more sensitive to memory side effects. We found that at the doses most used by doctors, the drug had no effect on any of the memory functions we tested.