Data Availability StatementAccess to anonymized individual participant-level data collected during the trial, in addition to supporting clinical documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Abstract Background Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; “type”:”clinical-trial”,”attrs”:”text”:”NCT02216214″,”term_id”:”NCT02216214″NCT02216214) described the efficacy and safety of mirabegron, a 3-adrenoreceptor agonist, for treatment of wet OAB in patients aged 65?years. This pre-planned analysis aimed to measure differences in cognitive function between mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA). Methods Outpatients aged 65?years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age ( 75/75?years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25?mg/day with an optional increase to 50?mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The MK-4827 pontent inhibitor study protocol was Independent Ethics Committee/Institutional Review Board-approved. Results Of the 887 randomized patients who received 1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged 75?years. All patients had 1 comorbidity and 94.3% were receiving 1 concomitant medication. Mctp1 One third of patients had a history of psychiatric disorders, the most common being depressive disorder (17.2%), insomnia (15.7%), and stress (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score? 26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (?0.2 [0.1]) or the placebo group (?0.1 [0.1]). Conclusions Treatment with mirabegron for 12?weeks did not contribute to drug-related cognitive side effects in patients aged 65?years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo. Trial registration “type”:”clinical-trial”,”attrs”:”text”:”NCT02216214″,”term_id”:”NCT02216214″NCT02216214 (prospectively registered August 13, 2014). (%)324 (73.3)317 (71.2)Age, mean??SD71.9??6.071.7??5.5Age?75?years, (%)124 (28.1)125 (28.1)BMI, kg/m2, mean??SD30.2??6.429.7??6.3?Category, (%)?? 2591 (20.6)108 (24.3)??25C 30150 (33.9)157 (35.3)??30201 (45.5)180 (40.4)Ethnicity, (%)?Not Hispanic or Latino395 (89.4)401 (90.1)?Hispanic or Latino43 (9.7)41 (9.2)?Unknown4 (0.9)3 (0.7)Race, (%)?White357 (80.8)348 (78.2)?Asian54 (12.2)59 (13.3)?Black or African American25 (5.7)33 (7.4)?Other6 (1.4)5 (1.1)Country, (%)?United Says389 (88.0)385 (86.5)?Canada53 MK-4827 pontent inhibitor (12.0)60 (13.5)Charlson Comorbidity Index score, mean??SD2.3 (1.2)2.3 (1.2)History of psychiatric disorders?Depressive disorder72 (16.3)81 (18.2)?Insomnia82 (18.6)57 (12.8)?Anxiety42 (9.5)59 (13.3)?Sleep disorder5 (1.1)6 (1.3)?Attention deficit/hyperactivity disorder4 (0.9)4 (0.9)?Libido decreased4 (0.9)4 (0.9)?Bipolar disorder3 (0.7)4 (0.9)?Nicotine dependence5 (1.1)1 (0.2)?Adjustment disorder with depressed mood2 (0.5)1 (0.2)?Initial insomnia02 (0.4)?Persistent depressive disorder02 (0.4)?Tension02 (0.4)?Main depression1 (0.2)1 (0.2)?Modification disorder01 (0.2)?Alcoholism01 (0.2)?Burnout symptoms01 (0.2)?Frustrated disposition01 (0.2)?Medication mistreatment01 (0.2)?Medication dependence01 (0.2)?Psychological disorder01 (0.2)?Disposition swings01 (0.2)?Nervousness01 (0.2)?Post-traumatic stress disorder01 (0.2)?Premature ejaculations01 (0.2)?Stress and anxiety disorder1 (0.2)0?Claustrophobia1 (0.2)0?Obsessive-compulsive disorder1 (0.2)0MoCA total scorea, MK-4827 pontent inhibitor (%)?Category, (%)??Regular (26)305 (69.3)310 (70.0)??Mild (18C25)103 (23.4)112 (25.3)??Average (10C17)3 (0.7)3 (0.7)??Serious ( 10)00??Missing29 (6.6)18 (4.1) Open up in another window Safety evaluation place (SAF): all randomized topics who received 1 dosage of study medicine Montreal Cognitive Evaluation, regular deviation a(%)overactive bladderselective serotonin reuptake inhibitors Baseline mean (regular mistake, SE) MoCA total ratings were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groupings, respectively (Desk?3). Among sufferers with MoCA data offered by baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group sufferers, respectively, had impaired cognitive function (MoCA total score? 26) at baseline (Fig.?1). Desk 3 Differ from baseline to EoT in MoCA check total rating (SAF) confidence period, end of treatment, Montreal Cognitive Evaluation, safety analysis established, standard mistake aend of treatment, Montreal Cognitive Evaluation. Impaired cognitive function?=?MoCA total rating? 26 [19] End of treatment There have been no adjustments in adjusted suggest (SE) MoCA total rating from baseline to EoT in the mirabegron group (?0.2 [0.1]) or the placebo group (?0.1 [0.1]) (Desk ?(Desk3).3). Adjustments in subscale ratings are proven in Desk?4. The amount of sufferers missing scores at EoT were 29 for placebo and 18 for the mirabegron total group. Of the 411 patients receiving placebo and 425 patients receiving mirabegron, 48 patients (24 in.