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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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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DOI: https://doi.org/10.1007/s11357-011-9357-7