Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study

Abstract

Background: Compared with younger people, the elderly are more likely to suffer from overactive bladder (OAB) and to have other chronic conditions that affect physical or cognitive function. Despite this, there are few data on the cognitive safety of antimuscarinic agents in older patients and none that examine the effect of these agents on those with mild cognitive impairment (MCI).

Objective: To evaluate cognitive effects during chronic stable dosing with solifenacin and oxybutynin versus placebo in older (≥75 yr) subjects with MCI.

Design, setting, and participants: A randomised, double-blind, triple-crossover trial in 26 elderly volunteers with MCI. Cognitive function was assessed using Cognitive Drug Research (CDR) computerised testing.

Intervention: Three treatment periods of 21 d each with solifenacin 5mg once daily, oxybutynin 5mg twice daily, or placebo, separated by 21-d washout periods.

Outcome measurements and statistical analysis: The primary end point was change from baseline in cognitive function with solifenacin at 6h postdose and oxybutynin at 2h postdose (time points close to their predicted time to peak concentration). Secondary end points included change in cognitive function at additional time points, and safety and tolerability assessments.

Results and limitations: Neither agent was associated with significant changes from baseline in any of the five standard, composite outcomes of cognitive function (power of attention, continuity of attention, quality of working memory, quality of episodic memory, and speed of memory). In a secondary analysis, oxybutynin was associated with significant decreases in power and continuity of attention versus placebo at 1-2h postdose. Both agents were well tolerated, with the most frequently reported adverse event being mild or moderate dry mouth.

Conclusions: Solifenacin had no detectable effect on cognition in this group of elderly people with MCI.

Trial registration: ClinicalTrials.gov NCT01126424.