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

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Abstract

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.

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Abbreviations

AD:

Alzheimer’s Disease

ADC:

Apparent diffusion coefficient

AxD:

Axial diffusivity

CC:

Corpus callosum

CSF:

Cerebrospinal fluid

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

GM:

Gray matter

HA:

Hyaluronan

HAS:

Hyaluronan synthase

MCI:

Mild cognitive impairment

MD:

Mean diffusivity

MRI:

Magnetic resonance imaging

OPC:

Oligodendrocyte progenitor cells

OL:

Oligodendrocyte

R 2 :

Transverse relaxation rate

RD:

Radial diffusivity

WM:

White matter

WMH:

White matter hyperintensities

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Acknowledgements

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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Authors and Affiliations

  1. Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR, USA

    Steven G. Kohama & Larry S. Sherman

  2. Boston University School of Medicine, Boston, MA, USA

    Douglas L. Rosene

  3. Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR, 97006, USA

    Larry S. Sherman

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  1. Steven G. Kohama
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  2. Douglas L. Rosene
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  3. Larry S. Sherman
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Correspondence to Larry S. Sherman.

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Kohama, S.G., Rosene, D.L. & Sherman, L.S. Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline. AGE 34, 1093–1110 (2012). https://doi.org/10.1007/s11357-011-9357-7

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