Association Between Polypharmacy and Physical Function in Middle-aged Adults: Findings from the CARDIA Function Study

J Gen Intern Med. 2025 Jul 7:10.1007/s11606-025-09692-3. doi: 10.1007/s11606-025-09692-3. Online ahead of print.

Abstract

Background: Polypharmacy (≥ 5 medications) and potentially inappropriate medications (PIM; per Beers criteria) are common in midlife. Polypharmacy and PIM use are associated with poor physical function and adverse health outcomes in older age, but the associations of polypharmacy and PIM use with physical function in middle-age are poorly understood.

Objective: Estimate the associations of polypharmacy and PIM use with physical performance in middle-age.

Design: Cross-sectional analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Function study.

Participants: The CARDIA prospective cohort study enrolled 5115 participants aged 18-30 in 1985-1986. We included participants with data on self-reported medication use who completed physical performance testing (gait speed, grip strength, 30-s chair stand, single-leg balance, 6-min walk test) at the year 35 in-person exam (2020-2022).

Main measures: The CARDIA Physical Performance (CAPP) score was calculated by assigning points to sex-specific quartiles for each test (0 = not attempted, 1-4 per quartile) and summing points across all five tests (0-20). We used multivariable linear regression to estimate the associations of polypharmacy and PIM use with CAPP score, adjusting for sociodemographics, multimorbidity, and physical activity history. For PIM use, a second model further adjusted for polypharmacy.

Key results: Among 1842 participants (age 60 years ± 4; 49% female, 44% Black race), 29% had polypharmacy and 25% used ≥ 1 PIM. Estimated CAPP score was 1.24 points lower among participants with polypharmacy vs. no polypharmacy (95% confidence interval [95%CI] -1.58, -0.90; p < 0.001). Estimated CAPP score was 0.88 points lower among participants with PIMs vs. no PIMs after initial adjustment (95%CI -1.22, -0.54; p < 0.001). After adjusting for polypharmacy, PIM use was not associated with CAPP score.

Conclusions: Polypharmacy is associated with lower physical function in middle-aged adults. Clinicians should consider systematically assessing physical function in middle-aged patients who have polypharmacy, to capture physical decline earlier in the lifespan.

Keywords: Middle-age; Physical function; Polypharmacy; Potentially inappropriate medications.