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

BackgroundCompared 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).ObjectiveTo evaluate cognitive effects during chronic stable dosing with solifenacin and oxybutynin versus placebo in older (≥75 yr) subjects with MCI.Design, setting, and participantsA randomised, double-blind, triple-crossover trial in 26 elderly volunteers with MCI. Cognitive function was assessed using Cognitive Drug Research (CDR) computerised testing.InterventionThree treatment periods of 21 d each with solifenacin 5 mg once daily, oxybutynin 5 mg twice daily, or placebo, separated by 21-d washout periods.Outcome measurements and statistical analysisThe primary end point was change from baseline in cognitive function with solifenacin at 6 h postdose and oxybutynin at 2 h 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 limitationsNeither 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 1–2 h postdose. Both agents were well tolerated, with the most frequently reported adverse event being mild or moderate dry mouth.ConclusionsSolifenacin had no detectable effect on cognition in this group of elderly people with MCI.