Can infections drive frailty? Insights from the Baltimore Longitudinal Study of Aging

BACKGROUND: Frail older people have elevated risk of developing infection. Whether a history of infections is associated with frailty and mortality has not been fully explored. This study investigates the associations between infection history, frailty and their coexistence on all-cause mortality. METHODS: Study used 1399 participants (mean age 65.3 years; 51.5% females) of the Baltimore Longitudinal Study of Aging where infection history was established by ICD-9 codes. Frailty was assessed using a 44-item Frailty Index (FI). The association between infection history and frailty was explored using multiple linear regression. Their association with mortality was assessed using Cox proportional hazard models. RESULTS: A history of any infections, and specific infections, including urinary tract, viral infection, pneumonia, and Herpes virus were associated with higher FI (p ≤ .01). Plasma leptin and BMI were positive mediators of the association between infection history and frailty. There was a significant association between infection history and FI progression (from FI < 0.12 to FI ≥ 0.12) in participants 65 years and older (HR: 1.43, 95% CI, 1.08-1.90, p = .02). Participants with both infections' history and high FI (FI ≥ 0.12) had higher risk of mortality (HR = 1.12; 95% CI, 1.05-2.10; p = .02) compared to those without history of infection and low FI. CONCLUSIONS: : A history of infections may accelerate the rate of frailty progression, defined as the transition from robustness to pre-frailty/frailty, and has an independent effect with frailty on increasing the risk of death. The mediating role of leptin suggests that obesity may be implicated in the relationship between history of infections and frailty.