Heterogeneous age-related breakdown of white matter structural integrity: Implications for cortical "disconnection" in aging and Alzheimer's disease

George Bartzokis, David Sultzer, Po H. Lu, Keith H. Nuechterlein, Jim Mintz, Jeffrey L. Cummings

Research output: Contribution to journalArticlepeer-review

286 Scopus citations


Human and non-human primate data suggest that the structural integrity of myelin sheaths deteriorates during normal aging, especially in the late-myelinating association regions and may result in "disconnection" of widely distributed neural networks. Magnetic resonance imaging (MRI) was used to assess the heterogeneity of this process and its impact on brain aging and Alzheimer's disease (AD) by evaluating early- and later-myelinating regions of the corpus callosum, the splenium (Scc) and genu (Gcc), respectively. Calculated transverse relaxation rates (R2), an indirect measure of white matter structural integrity for the Gcc and Scc, were examined. The relationship between age and R2 differed in the two regions. A quadratic (inverted U) function with an accelerating rate of decline beginning at age 31 best represented the Gcc pattern while the Scc decline was three-fold smaller, gradual, and linear. These data suggest that the severity of age-related myelin breakdown is regionally heterogeneous, consistent with the hypothesis that differences in myelin properties make later-myelinating regions more susceptible to this process. In AD this process is globally exacerbated, consistent with an extracellular deleterious process such as amyloid β-peptide toxicity. Non-invasive measures such as R2 may be useful in primary prevention studies of AD.

Original languageEnglish (US)
Pages (from-to)843-851
Number of pages9
JournalNeurobiology of Aging
Issue number7
StatePublished - Aug 1 2004
Externally publishedYes


  • Aging
  • Alzheimer
  • Amyloid
  • Corpus callosum
  • Degeneration
  • MRI
  • Myelin
  • Oligodendrocyte
  • Prevention
  • Relaxation
  • Toxic
  • White matter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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