Lifestyle, biological, and genetic factors related to brain iron accumulation across adulthood

Neurobiol Aging. 2024 Dec:144:56-67. doi: 10.1016/j.neurobiolaging.2024.09.004. Epub 2024 Sep 10.

Abstract

Iron is necessary for many neurobiological mechanisms, but its overaccumulation can be harmful. Factors triggering age-related brain iron accumulation remain largely unknown and longitudinal data are insufficient. We examined associations between brain iron load and accumulation and, blood markers of iron metabolism, cardiovascular health, lifestyle factors (smoking, alcohol use, physical activity, diet), and ApoE status using longitudinal data from the IronAge study (n = 208, age = 20-79, mean follow-up time = 2.75 years). Iron in cortex and basal ganglia was estimated with magnetic resonance imaging using quantitative susceptibility mapping (QSM). Our results showed that (1) higher peripheral iron levels (i.e., composite score of blood iron markers) were related to greater iron load in the basal ganglia; (2) healthier diet was related to higher iron levels in the cortex and basal ganglia, although for the latter the association was significant only in younger adults (age = 20-39); (3) worsening cardiovascular health was related to increased iron accumulation; (4) younger ApoE ε4 carriers accumulated more iron in basal ganglia than younger non-carriers. Our results demonstrate that modifiable factors, including lifestyle, cardiovascular, and physiological ones, are linked to age-related brain iron content and accumulation, contributing novel information on potential targets for interventions in preventing brain iron-overload.

Keywords: Aging; Brain iron; Cardiovascular risk; Lifestyle; Longitudinal; Quantitative susceptibility mapping (QSM).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aging* / genetics
  • Aging* / metabolism
  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / metabolism
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Diet
  • Female
  • Humans
  • Iron Overload / genetics
  • Iron Overload / metabolism
  • Iron* / metabolism
  • Life Style*
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Iron