Polypharmacy and cognitive outcomes in elderly inpatients with Alzheimer’s disease: A three-year retrospective study

Background: Inpatient care for Alzheimer's disease (AD), often complicated by comorbidities, frequently involves polypharmacy (?5 medications). The profile and cognitive consequences of sustained polypharmacy in these elderly inpatients require further investigation. Objectives: To investigate the status of polypharmacy in elderly inpatients with AD and its correlation with three-year cognitive outcomes, so as to provide a basis for clinical optimization of medication regimens. Methods: This study was a retrospective propensity score matching (PSM) cohort study. 300 AD inpatients who were hospitalized from March 2022 to March 2025 were included. Patients were stratified into polypharmacy and non-polypharmacy groups according to their polypharmacy status. The primary outcome was the incidence of cognitive decline (MMSE decline ?3 points) at 3 years. Secondary outcomes were the association of CDR progression, rate of decline in MoCA, incidence of falls, all-cause rehospitalization, all-cause mortality and anticholinergic drug burden with cognitive outcomes. Results: After PSM, baseline characteristics were balanced (p>0.05). At the 3-year follow-up, the polypharmacy group had a significantly higher incidence of cognitive decline than the non-polypharmacy group (64.0% vs. 38.0%; RR=1.68, 95% CI: 1.33-2.13, p<0.001). Polypharmacy was also associated with faster CDR progression, a greater annual rate of MoCA decline and increased risks of falls (RR=1.82, p<0.01) and all-cause rehospitalization (RR=1.67, p<0.001). A high anticholinergic burden (ACB score ?3) was identified as an independent predictor of cognitive decline (OR=2.5, 95%CI: 1.7-3.7, p<0.001). Conclusions: Our findings highlight polypharmacy as a key, modifiable risk for cognitive decline in AD, calling for structured medication management to mitigate this risk.