Age-related changes in white matter are likely not due to demyelination?

That’s the conclusion of an important new paper from Billiet et al that integrated a bunch of different imaging modalities.

First, they used DTI to measure fractional anisotropy, which is a non-specific measure of white matter, measuring axon density, axon diameter, and myelin content. They also used myelin water fraction (MWF) to measure myelin content and the orientation dispersion index (ODI) to measure dendrite/axon dispersion. These were their findings:

  • Total white matter volume does not change in aging
  • Myelin content (via MWF) is not significantly altered in aging in most regions, and in the regions where there is a change, it increases
  • There is a widespread decrease in fractional anisotropy in aging that is especially strong in frontal regions
  • Changes in myelin content (MWF) do not correlate well with this decrease in fractional anisotropy
  • Changes in neurite orientation (ODI) dispersion do correlate with this decrease in fractional anisotropy

Thus, their conclusion is that age-related decreases in the “diffusibility” of white matter (or whatever fractional anisotropy is measuring) are due to changes in axons rather than to changes in myelin.

It’s all cross-sectional, n = 59, and they call this conclusion “highly speculative,” but if true it suggests that axons changes are more early/causal/fundamental to aging than changes in myelin. We need more data on this, especially from older individuals (their study went up to only 70) and from people with dementias, such as Alzheimer’s disease.

Billiet T, Vandenbulcke M, Mädler B, et al. Age-related microstructural differences quantified using myelin water imaging and advanced diffusion MRI. Neurobiol Aging. 2015