Progression and trajectory network of age-related functional impairments and their associations with mortality: a two-decade prospective study

ABSTRACT Objective To characterize the progression and trajectory network of age-related functional impairments and assess their associations with mortality. Design Prospective cohort study. Setting The Health and Retirement Study (HRS, 2000-2020). Participants A total of 17 914 HRS participants aged from 51 to 90 years in 2000. Main outcome measure Age-related functional impairments including visual impairment, hearing impairment, cognitive impairment, physical frailty, restless sleep, and depression, all measured using structural questionnaires biennially or quadrennially. All-cause mortality was ascertained from multiple sources. Results During follow-up (median=12 years), the incidence rates of visual impairment (59.3 cases/1000 person years), hearing impairment (52.1 cases/1000 person years), physical frailty (31.7 cases/1000 person years), and cognitive impairment (42.5 cases/1000 person years) increased exponentially with age ( P -trend <0.001), while those of restless sleep (75.6 cases/1000 person years) and depression (35.6 cases/1000 person years) increased relatively slowly. We detected bidirectional associations among all ARFIs ( P <0.001). Overall, each additional ARFI was associated with 13% (11%-15%) higher risk of mortality, with independent associations observed for physical frailty (hazard ratio: 1.59, 95% confidence interval: 1.49-1.69), depression (1.38, 1.30-1.46), visual impairment (1.19, 1.13-1.26), and cognitive impairment (1.13, 1.06-1.21). Conclusions ARFIs were highly interconnected as a network and were associated with mortality, which highlighted the importance of integrated strategies to monitor and manage the ARFIs to achieve healthy longevity. SUMMARY BOXES WHAT IS ALREADY KNOWN ON THIS TOPIC Aging is characterized by changes in multiple functions, such as visual, hearing, and cognitive impairments. Specific age-related functional impairments are associated bidirectionally. WHAT THIS STUDY ADDS In a prospective study, the incidence rates of visual impairment, hearing impairment, physical frailty, and cognitive impairment increased exponentially as age increased, while incidence rates of restless sleep and depression increased relatively slowly with age. The six ARFIs are bidirectionally related to each other and predicted higher risk of mortality in a dose-response manner, with independent associations observed for visual impairment, cognitive impairment, physical frailty, and depression.