Inflammation, Depression, and Slow Gait: A High Mortality Phenotype in Later Life

Background. Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality. Methods. Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression >= 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality. Results. For each outcome, low-probability (n(inflammation) = 1,656, n(slow gait) = 1,471, n(depression) = 1,458), increasing-probability (n(inflammation) = 847, n slow gait = 880, n(depression) = 1,062), and consistently high-probability (n(inflammation) = 572, n(slow gait) = 724, n(depression) = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r=.40, p<.001) and depression (r=.49, p<.001). Although worsening trajectories of inflammation were independently associated with mortality (p<.001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p<.01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations. Conclusions. Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed.