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.
Keywords: Alzheimer's disease; Cognitive decline; Incidence rate; Polypharmacy; Propensity score matching; Risk factors.