Polypharmacy, drug-drug interactions, anticholinergic burden and cognitive outcomes: a snapshot from a community-dwelling sample of older men and women in northern Italy

Abstract

Abstract Introduction Polypharmacy (PP) use is very common in older people and may lead to anticholinergic burdens that affect cognitive impairment. We aimed to determine the occurrence of PP, drug-drug interactions (DDIs) and anticholinergic burden (ACB) and their role in cognitive outcomes in Italian older population. Methods Cross-sectional data from 636 community-dwelling adults (73.2±6.0 SD, 58.6% women) participating in the NutBrain study (2019-2023) were analyzed. Participants were asked about their medication use, and data on DDIs and ACB were extracted. The association of PP (≥ 5 drugs/day), DDIs, and ACB with mild cognitive impairment (MCI) and specific cognitive domains was assessed using logistic regression adjusted for confounders. Sex-stratified analysis was performed. Results Overall, 27.2% of the participants were exposed to PP, 42.3% to DDIs and 19% to cumulative ACB. Women were less exposed to PP and more exposed to ACB than men. In multivariate analysis, the odds of having MCI (24%) were three times higher in those with severe ACB ( ≥ 3) (OR 3.34, 95%CI 1.35-8.25). ACB was positively associated with poor executive function (OR 4.45, 95%CI 1.72-11.49) and specifically with FAB and phonological and semantic fluency. In a stratified analysis by sex, ACB was statistically significantly associated with MCI and executive function in women and with memory in men. Conclusions PP, DDIs and anticholinergic (AC) use are very common in community-dwelling older people. AC exposure is associated with MCI, especially poor executive function. Further sex-stratified longitudinal neuroimaging studies are warranted. Clinicians are encouraged to be vigilant when prescribing anticholinergics. Trial registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov).