Midlife cumulative deficit frailty predicts Alzheimer’s disease-related plasma biomarkers in older adults Journal Article uri icon

Overview

abstract

  • Abstract; ; Background; The study explores whether frailty at midlife predicts mortality and levels of biomarkers associated with Alzheimer’s disease and related dementias (ADRD) and neurodegeneration by early old age. We also examine the heritability of frailty across this age period.; ; ; Methods; Participants were 1,286 community-dwelling men from the Vietnam Era Twin Study of Aging at average ages 56, 62 and 68, all without ADRD at baseline. The cumulative deficit frailty index (FI) comprised 37 items assessing multiple physiological systems. Plasma biomarkers at age 68 included beta-amyloid (Aβ40, Aβ42), total tau (t-tau) and neurofilament light chain (NfL).; ; ; Results; Being frail doubled the risk of all-cause mortality by age 68 (OR = 2.44). Age 56 FI significantly predicted age 68 NfL (P = 0.014), Aβ40 (P = 0.001) and Aβ42 (P = 0.023), but not t-tau. Age 62 FI predicted all biomarkers at age 68: NfL (P = 0.023), Aβ40 (P = 0.002), Aβ42 (P = 0.001) and t-tau (P = 0.001). Age 68 FI scores were associated with age 68 levels of NfL (P = 0.027), Aβ40 (P < 0.001), Aβ42 (P = 0.001) and t-tau (P = 0.003). Genetic influences accounted for 45–48% of the variance in frailty and significantly contributed to its stability across 11 years.; ; ; Conclusions; Frailty during one’s 50s doubled the risk of mortality by age 68. A mechanism linking frailty and ADRD may be through its associations with biomarkers related to neurodegeneration. Cumulative deficit frailty increases with age but remains moderately heritable across the age range studied. With environmental factors accounting for about half of its variance, early interventions aimed at reducing frailty may help to reduce risk for ADRD.;

publication date

  • March 1, 2024

has restriction

  • closed

Date in CU Experts

  • July 4, 2024 12:25 PM

Full Author List

  • Buchholz E; Gillespie NA; Hunt JF; Reynolds CA; Rissman RA; Schroeder A; Cortes I; Bell T; Lyons MJ; Kremen WS

author count

  • 11

Other Profiles

International Standard Serial Number (ISSN)

  • 0002-0729

Electronic International Standard Serial Number (EISSN)

  • 1468-2834

Additional Document Info

volume

  • 53

issue

  • 3