Pattern of normal age-related regional differences in white matter microstructure is modified by vascular risk

Brain Res. 2009 Nov 10;1297:41-56. doi: 10.1016/j.brainres.2009.08.058. Epub 2009 Aug 25.


Even successful aging is associated with regional brain shrinkage and deterioration of the cerebral white matter. Aging also brings about an increase in vascular risk, and vascular impairment may be a potential mechanism behind the observed patterns of aging. The goals of this study were to characterize the normal age differences in white matter integrity in several brain regions across the adult life span and to assess the modifying effect of vascular risk on the observed pattern of regional white matter integrity. We estimated fractional anisotropy and diffusivity of white matter in nine cerebral regions of interest in 77 healthy adults (19-84 years old). There was a widespread reduction of white matter anisotropy with age, and prefrontal and occipital regions evidenced the greatest age-related differences. Diffusivity increased with age, and the magnitude of age differences increased beginning with the middle of the fifth decade. Vascular risk factors modified age differences in white matter integrity. Clinically diagnosed and treated arterial hypertension was associated with reduced white matter anisotropy and increased diffusivity beyond the effects of age. In the normotensive participants, elevation of arterial pulse pressure (a surrogate of arterial stiffness) was linked to deterioration of the white matter integrity in the frontal regions. Although the causal role of vascular risk in brain aging is unclear, the observed pattern of effects suggests that vascular risk may drive the expansion of age-related white matter damage from anterior to posterior regions.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Blood Pressure / physiology
  • Brain Mapping / methods
  • Cerebral Arteries / pathology*
  • Cerebral Arteries / physiopathology
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / pathology*
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / pathology
  • Cerebrovascular Disorders / physiopathology
  • Dementia, Vascular / etiology
  • Dementia, Vascular / pathology*
  • Dementia, Vascular / physiopathology
  • Diffusion Tensor Imaging / methods
  • Disease Progression
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Risk Factors
  • Severity of Illness Index
  • Young Adult