Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging

Neurobiol Aging. 2014 Aug;35(8):1862-72. doi: 10.1016/j.neurobiolaging.2014.02.008. Epub 2014 Feb 15.


A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.

Keywords: 3T; Aging; MT; Magnetization transfer; Quantitative; R1; R2*; Relaxation; T1; T2*; VBQ; Water content.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / pathology*
  • Brain / metabolism
  • Brain / pathology*
  • Female
  • Humans
  • Iron / metabolism
  • Iron Metabolism Disorders / metabolism
  • Iron Metabolism Disorders / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neuroaxonal Dystrophies / metabolism
  • Neuroaxonal Dystrophies / pathology
  • Neuroimaging / methods*
  • Young Adult


  • Iron

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)