, Volume 34, Issue 5, pp 1093–1110 | Cite as

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

  • Steven G. Kohama
  • Douglas L. Rosene
  • Larry S. Sherman


The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in humans, that these disturbances contribute to age-related cognitive decline, and that age-related WM changes may occur as a result of free radical damage, degenerative changes in cells in the oligodendrocyte lineage, and changes in microenvironments within WM.


Aging White matter Myelination 



Alzheimer’s Disease


Apparent diffusion coefficient


Axial diffusivity


Corpus callosum


Cerebrospinal fluid


Diffusion tensor imaging


Fractional anisotropy


Gray matter




Hyaluronan synthase


Mild cognitive impairment


Mean diffusivity


Magnetic resonance imaging


Oligodendrocyte progenitor cells




Transverse relaxation rate


Radial diffusivity


White matter


White matter hyperintensities



This work was supported in part by NIH grants R01 AG031892 (LSS); P51 RR000163 (LSS and SGK; Oregon National Primate Research Center Grant); P01 AG000001 (DLR), R01 AG021133 (DLR), P51 RR000165 (DLR; Yerkes Primate Center Grant).


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Copyright information

© American Aging Association 2011

Authors and Affiliations

  • Steven G. Kohama
    • 1
  • Douglas L. Rosene
    • 2
  • Larry S. Sherman
    • 1
    • 3
  1. 1.Oregon National Primate Research CenterOregon Health and Science UniversityPortlandUSA
  2. 2.Boston University School of MedicineBostonUSA
  3. 3.Division of NeuroscienceOregon National Primate Research CenterBeavertonUSA

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