Dementia Associated with Anticholinergic Drugs Used for Overactive Bladder: A Nested Case-Control Study Using the French National Medical-Administrative Database

Abstract

Purpose:We analyzed the relationship between use of anticholinergic drugs to treat overactive bladder (OAB) and risk of incident dementia in older patients, overall and for each drug separately.Materials and Methods:We conducted a nested case-control study using the French National Medical-Administrative Database. We identified incident dementia cases and controls from January 1, 2013 to December 31, 2018 in individuals aged ≥60 years. Controls were matched 5:1 to cases by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure period ending 2 years before the index date (lag-time period to avoid protopathic bias). We quantified cumulative exposure to flavoxate, oxybutynin, solifenacin, trospium, and fesoterodine using defined daily doses (DDDs). We performed conditional logistic regression analyses adjusted for factors known to be associated with OAB and/or dementia including obesity, diabetes, stroke, coronary heart disease, and psychotic disorders.Results:We analyzed 4,810 cases and 24,050 matched controls with a median age of 82 years. OAB anticholinergic use was associated with an increased risk of dementia (adjusted OR [aOR]=1.23, 95% CI 1.10–1.37) with a cumulative dose-response: aOR=1.07 (95% CI 0.91–1.25) for 1-90 DDDs, aOR=1.29 (1.05–1.58) for 91–365 DDDs and aOR=1.48 (1.22–1.80) for >365 DDDs. Considering each OAB anticholinergic separately showed a particularly marked increased risk of dementia for oxybutynin and solifenacin, but no increased risk for trospium.Conclusions:When treating OAB in older patients, OAB anticholinergics should be used with caution, taking into account the patient's cognitive status, the anticholinergic load, and the different therapeutic options.

An Analysis of Stated Insurance Coverage and Estimated Patient-Incurred Costs of Treatments for Lower Urinary Tract Symptoms

“…Antimuscarinics demonstrate treatment efficacy for OAB but have frequent adverse effects (dry mouth, constipation) that lower persistence. As OAB prevalence increases with age, 16 recent studies detailing increased dementia risk 17–19 and dose-dependent associations with brain atrophy, cognitive impairments, and clinical decline with anticholinergics are concerning 17 . Oxybutynin, a nonselective anticholinergic, is the only option covered by all plans at low price, but many health care providers are reticent to prescribe it for fear of cognitive sequelae, particularly in older patients 20 .…”

SUFU white paper on overactive bladder anticholinergic medications and dementia risk

“…The authors found higher mortality (hazard ratio [HR] 1.55, p = 0.001) and cognitive decline in patients treated with high central anticholinergic burden. Another recent retrospective study found increased risk of dementia with >90 days exposure with oxybutynin and solifenacin but not trospium 33 …”

“…Another recent retrospective study found increased risk of dementia with >90 days exposure with oxybutynin and solifenacin but not trospium. 33 2.5 | Clinicians should consider potential cognitive risks in all patient populations when prescribing OAB anticholinergics for chronic use…”

Dementia Associated with Anticholinergic Drugs Used for Overactive Bladder: A Nested-Case Control Study Using the French National Medical-Administrative Database. Letter.

“…To the Editor: Malcher et al conducted a nested case-control study to evaluate the relationship between the use of anticholinergic drugs for overactive bladder (OAB) and incident dementia in older patients with a median age of 82. 1 A 1:5 matching procedure for diagnostic date, age, sex, and income was performed, and conditional logistic regression analysis was adopted. Defined daily doses were used for the dose-response relationship, and adjustments for obesity, diabetes, stroke, coronary heart disease, and psychotic disorders were made.…”