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Kroger E, VanMarum R, Souverein P, Carmichael PH, Egberts T. Pharmacoepidemiol Drug Saf. 2015 Mar; 24 (3): 276-85.

BACKGROUND: Treatment of Alzheimer disease (AD) with cholinesterase inhibitors (ChEIs) may increase the risk of urinary incontinence (UI). OBJECTIVE: To assess whether ChEI use was associated with the risk of UI among older patients with AD. METHOD: A crossover cohort study using the PHARMO Record Linkage System included 10 years of data on drug dispensing histories for over two million Dutch residents. Included patients were aged 50 +, free of UI for the last 6 months, received a first ChEI prescription during the study period, had at least 12 months prior drug exposure history and one subsequent prescription of any drug. UI was defined as a first dispensing of a urinary spasmolytic or of incontinence products for at least 30 days. Cox regression with time-varying covariates and multivariate adjustment allowed assessing whether UI incidence was associated with ChEI exposure. RESULTS: Among 3154 patients there were 657 UI cases during a mean follow-up of 5.1 years before a first ChEI dispensing,and 499 cases after ChEI initiation, during a mean follow-up of 2.0 years. Among the 2700 participants free of UI one year before ChEI initiation, the adjusted hazard ratio (HR) for UI was 1.13 (95% CI: 0.97-1.32) when periods with ChEI use were compared to periods without ChEI use. Sensitivity analyses may suggest an increased risk in the 1(st) month after ChEI initiation (HR: 1.72, p = 0.09) CONCLUSION: Worsening AD may increase incidence of UI, but no firm association between ChEI treatment and riskof UI could be shown from these data. Copyright (c) 2015 John Wiley & Sons, Ltd.