Abstract 031: Age-related Homeostatic Dysregulation In Midlife And Physical Function In Late Life: The Atherosclerosis Risk In Communities (aric) Study

Abstract

Introduction: Age-related homeostatic dysregulation (Dm), characterized by multi-biomarker composite measures, has shown promise as a rate-of-aging metric. We tested the association of midlife Dm and its change over ~20 years of follow-up with later life physical function. Methods: We studied 4617 ARIC cohort participants (mean age 54.8 years, 58% female, 20% Black) who completed in-person examinations from 1990-92 (baseline) through 2011-13. Dm quantifies the multivariate statistical deviation of 15 physiology-motivated biomarkers from the distribution in a healthy sample at baseline. Midlife Dm was grouped by quartiles (higher quartiles indicating greater homeostatic dysregulation) and temporal change in Dm was quantified continuously. Physical function was assessed in 2011-13 and included measures from the Short Physical Performance Battery (SPPB) including repeated chair stands, balance, 4-meter walk and grip strength. Associations were quantified using linear regression and ordinal logistic regression as applicable, adjusting for age, sex, race, and education. Results: A graded association was observed between midlife Dm and physical functional performance in late life (Table). Compared to the 1 st quartile of midlife Dm, the odds ratio of a lower SPPB score in late life was 1.19 (95%CI 1.04, 1.35) for the 2 nd quartile, 1.63 (1.41, 1.90) for the 3 rd quartile, and 3.14 (2.60, 3.79) for the 4 th quartile. Similar associations were observed for each of SPPB components and grip strength, either modeled ordinally or continuously. Each standard deviation increase in 10-year Dm change was associated with ~2-3 times the odds of having a poorer physical functional performance. Conclusions: Greater homeostatic dysregulation at midlife and increases in dysregulation during follow-up were associated with poorer physical function in late life. Insights into the factors that lead to progression of multisystem deterioration during midlife may highlight opportunities to preserve functional abilities in late life.