Abstract
OBJECTIVES: This study aimed to analyze the associations of the Phenotypic Aging Index (PAI) with health outcomes, functional outcomes, and health care utilization using UK Biobank data. Specifically, we assessed whether the PAI predicts these outcomes after adjusting for polygenic risk scores (PRS) and demographic and socioeconomic variables.</p>
DESIGN: This was a prospective cohort study with no intervention.</p>
SETTING AND PARTICIPANTS: We analyzed data from 13,879 individuals aged ≥60 years in the UK Biobank.</p>
METHODS: The PAI was constructed based on 4 domains: body composition, energetics, homeostatic mechanisms, and neurodegeneration. Health outcomes included mortality, multimorbidity, and disability; functional outcomes included physical and cognitive function; and health care utilization outcomes included long-term hospitalization and nursing home admission. Cox proportional hazards models and logistic regression analyses were used to examine associations. Covariates included age, sex, ethnicity, household income, education, alcohol consumption frequency, smoking status, and PRS.</p>
RESULTS: The PAI significantly predicted mortality (hazard ratio, 1.84; 95% CI, 1.26-2.70), multimorbidity [odds ratio (OR), 1.69; 95% CI, 1.48-1.93], disability (OR, 1.36; 95% CI, 1.190-1.57), physical function decline (OR, 4.48; 95% CI, 3.21-6.22), and long-term hospitalization (OR, 1.29; 95% CI, 1.00-1.66). Interaction analyses showed a stronger association of the PAI with multimorbidity and physical function decline in women. Models that included the PAI showed improved predictive performance for these outcomes.</p>
CONCLUSIONS AND IMPLICATIONS: The PAI is a significant predictor of adverse health, functional, and health care utilization outcomes and enhances predictive accuracy. Its greater impact on multimorbidity and physical function decline in women suggests the need for sex-specific aging interventions.</p>