Mild polypharmacy and MCI progression in older adults: the mediation effect of drug-drug interactions

Background: Polypharmacy has been associated with worse cognitive performance, but its impact on mild cognitive impairment (MCI) progression to dementia has not been explored. Aims: The aims of the study were to investigate the association between multidrug regimens and MCI progression, and the possible mediation of drug-drug interactions and drugs' anticholinergic effect in such association. Methods: This work included 342 older adults with MCI, who were involved in an Italian multicenter population-based cohort study. Information on drugs taken was derived from general practitioners' records and data on drug-drug interactions and anticholinergic burden [evaluated through the Anticholinergic Cognitive Burden and the Anticholinergic Risk Scale (ARS)] were extracted. Multinomial logistic regressions assessed the associations between mild polypharmacy (>= 3 drugs/day), drug-drug interactions, and anticholinergic burden with MCI changes after 1-year follow-up. Mediation analysis evaluated potential mediators of that relationship. Results: Approximately, 50% of participants took >= 3 drugs/day. During the follow-up, 4.1% of MCI patients progressed to dementia. The odds of developing dementia was sixfold higher in those who took >= 3drugs/day (OR = 6.04, 95% CI 1.19-30.74), eightfold higher in those with >= 1 drug-drug interaction/s (OR = 8.45, 95% CI 1.70-41.91), and fivefold higher in those with ARS >= 1 (OR = 5.10, 95% CI 1.04-24.93). Drug-drug interactions mediated 70.4% of the association between medication number and MCI progression to dementia (p = 0.07). Discussion: Our study suggests that even mild polypharmacy may increase the risk of MCI progression to dementia, probably due to the presence of drug-drug interactions, which often occur in multidrug regimens. Conclusions: Older people require careful management of pharmacological treatments, with special attention to drug-drug interactions and drug-related anticholinergic effects.