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

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.

Anticholinergic Activity of Psychotropic Drugs and Cognitive Impairment Among Participants Aged 45 and Over: The CONSTANCES Study.

INTRODUCTION: Psychotropic drugs such as anxiolytics, antidepressants and antipsychotics may have anticholinergic properties that could directly affect patients' cognition. OBJECTIVES: Our objective was to assess the relationship between exposure to anticholinergic-positive (AC+) psychotropic drugs and cognitive impairment compared with psychotropic drugs without anticholinergic activity (AC-). METHODS: This analysis included participants (aged 45-70 years) enrolled between January 2012 and October 2017 in the CONSTANCES cohort treated with psychotropic drugs (antidepressants n = 2602, anxiolytics n = 1195, antipsychotics n = 197) in the 3 years preceding cognitive assessment. Within each drug class, the Anticholinergic Cognitive Burden scale was used to classify drugs as either AC+ or AC-. Cognitive impairment was defined as a score below - 1 standard deviation from the standardized mean of the neuropsychological score. We used multiple logistic regression models and matching on propensity score to estimate the relationship between anticholinergic activity and cognitive impairment. RESULTS: Our analyses did not show any increased risk of cognitive impairment for AC+ antidepressants and anxiolytics, with the exception of a slight increase for AC+ antidepressants in episodic memory (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.05-1.36). Conversely, we found a more marked increase in risk with AC+ antipsychotics on executive function (Trail Making Test-A [TMT-A], OR 4.49 [95% CI 2.59-7.97] and TMT-B, OR 3.62 [95% CI 2.25-5.89]). CONCLUSION: Our results suggest there is no clinically relevant association between the anticholinergic activity of antidepressant and anxiolytic drugs and cognitive impairment in middle-aged adults. An association could exist between AC+ antipsychotics and executive function.

Anticholinergic drug use and cognitive performances in middle age: findings from the CONSTANCES cohort.

BACKGROUND: Previous studies have shown associations between the use of anticholinergics (AC) and cognitive performance in the elderly, considering AC as a homogeneous set of drugs. The present study aims to assess the relationship between exposure to AC drugs and cognitive performance in middle-aged adults according to AC potency and drug class. METHODS: Our cross-sectional study used baseline data of 34 267 participants aged 45-70 from the Consultants des centres d'examen de santé de la sécurité sociale (CONSTANCES) cohort. The cumulative exposure to AC was measured using national reimbursement databases over the 3-year period preceding assessment of cognitive performance. Eight classes of AC drugs were differentiated. Episodic verbal memory, language abilities and executive functions were evaluated by validated neuropsychological tests. Analyses were controlled on lifestyle and health status variables. RESULTS: This study showed a negative association between overall cumulative AC exposure and cognitive performances after adjustment. The use of drugs with possible AC effect according to the Anticholinergic Cognitive Burden scale (ACB-1 score) was only associated with executive functions. Analyses of AC exposure across drug classes showed a negative association between the use of AC antipsychotics and all cognitive functions assessed. Heterogeneous associations were found for the use of AC anxiolytics, AC opioids and AC drugs targeting the gastrointestinal tract or metabolism. We did not find significant associations between the use of antihistamines, antidepressants, cardiovascular system or other AC medications and cognitive function. CONCLUSION: Association between AC drugs and cognitive performance was highly heterogeneous across drug classes; this heterogeneity will have to be considered by future studies.

Intergenerational Socioeconomic Mobility and Adult Depression: The CONSTANCES Study.

ABSTARCT: Using data from the nationally representative Consultants des Centres d'Examens de Santé (CONSTANCES) study in France (2012-2014; n = 67,057), we assessed the relationship between intergenerational socioeconomic mobility and adult depression (Center for Epidemiological Studies-Depression Scale scores of ≥16 in men or ≥20 in women) and antidepressant use. Socioeconomic position was ascertained by occupational grade (childhood: maternal and paternal measures prior to age 15 years combined; adulthood: participant's own). We used logistic regression models adjusted for sociodemographic characteristics, parental history of psychiatric disorders and suicide, health behaviors, and chronic health problems. Compared with the reference group (persistently high socioeconomic circumstances), participants in other groups had elevated levels of depression (for upward mobility, multivariate odds ratios (OR) = 1.21; intermediate socioeconomic position, 1.28; downward mobility, 1.66; persistently low socioeconomic position, 1.82). Downward mobility and persistently low socioeconomic position were also associated with elevated odds of antidepressant use (for downward mobility, multivariate OR = 1.24; for persistently low socioeconomic position, 1.36). In supplementary analyses, the association of socioeconomic mobility with depression was stronger in women than in men and among younger participants (aged 18-29 years) than among older participants. Factors that contribute to depression risk and socioeconomic inequalities in this area appeared to be at play already in childhood; this should be acknowledged by clinicians and policymakers.