Research Connections · Jul 2026
Association of polypharmacy with cognitive decline and mortality in the oldest old: findings from the Newcastle 85+ study
By Maheshwari V, Robinson L, Kingston A
Abstract The oldest old experience high rates of polypharmacy and cognitive impairment. While polypharmacy is suspected to accelerate cognitive decline, evidence is frequently limited by cross-sectional designs and informative censoring due to high mortality. This study investigated the longitudinal association between polypharmacy, cognitive decline, and mortality in the oldest old. Data from 843 participants (aged 85 at baseline) from the Newcastle 85+ Study were analyzed across five waves covering a 10-year follow-up. Medication count was used as a continuous time-varying exposure in the primary analysis and categorized for sensitivity analyses. Cognitive function was assessed using the Mini-Mental State Examination. A Bayesian joint modelling approach was used to simultaneously estimate longitudinal cognitive trajectories and mortality risk, adjusting for sociodemographic factors and time-varying health covariates. In the fully adjusted joint model, a significant interaction between time and medication count was observed [β = −0.03, 95% credible interval (CI) − 0.05 to −0.01], with each additional medication steepening the annual rate of cognitive decline by approximately 0.03 MMSE points. However, medication count was not significantly associated with mortality (hazard ratio, HR = 1.02, 95% CI 0.97–1.07). Sensitivity analyses were consistent with the primary analysis. Physical inactivity and disability were also strongly associated with both outcomes. Polypharmacy is modestly associated with accelerated cognitive decline in the oldest old but is not associated with mortality once health covariates are accounted for. Future research should use larger cohorts, richer medication classification, adherence measures, and cognitive assessments capable of examining domain-specific decline.