Objective To investigate the association between the medication exposure, measured by the polypharmacy/excessive polypharmacy and the anticholinergic and/or sedative drug exposure, on frailty status among French older community-dwelling patients. Setting day-care unit in France (Lyon), with retrospective data from July, 2017 to March, 2018. Method This monocentric cross-sectional study included community-dwelling patients aged 65 years and over and admitted at the day-care unit for a geriatric evaluation. Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and excessive polypharmacy were defined as the concomitant use of 5-9 and 10 or more drugs, respectively. The cumulative anticholinergic and sedative exposure was measured using the drug burden index (DBI). The DBI score was presented in 4 differentiated scores: a null score (DBI = 0), a combined score (anticholinergic and sedative score), an anticholinergic score, and a sedative score. The association between medication and frailty was assessed by logistic regression models controlled for multiple potential confounders. Main outcome measure Association between medication exposure (polypharmacy, anticholinergic and sedative exposure) and frailty. Results In this study, 403 patients were included: 44.7% were frail and 40.7% were pre-frail. Polypharmacy and excessive polypharmacy affected 44.7% and 17.1% of the population respectively. The mean DBI was 0.33 ± 0.43, with 16.4% of patients with only sedative exposure, 9.7% with only anticholinergic exposure and 33.0% with both exposures. After adjustment, polypharmacy and excessive polypharmacy were associated with frailty with adjusted odds ratios (95% confidence interval) of 2.18 (1.03-4.22) and 2.72 (1.01-7.37) respectively. The cumulative exposure to anticholinergic and sedative drugs (combined score) was significantly associated to an increased risk for frailty with adjusted odds ratios (95% confidence interval) of 3.54 (1.47-8.57). Conclusion The study showed that polypharmacy and cumulative anticholinergic and sedative exposure are associated with frailty. Further research should address the potential benefit of collaborative medication review for preventing medication-associated frailty.

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