Abstract Details

Human and non-human primate studies have shown that during normal aging, the structural integrity of myelin sheaths leads to the "disconnection" of distributed neural networks, resulting in cognitive decline. Similar evidence in humans comes from diffusion tensor imaging (DTI), which lacks specificity to myelin or axons, leading to inconsistent associations with cognition. Here, we estimated myelin water fraction (MWF) using myelin water imaging to test the hypothesis that lower MWF would relate to lower cognitive scores.

To provide evidence for the "myelin" or "disconnection" hypothesis of cognitive aging. 

We collected 3D GRASE and DTI MRI data from 140 participants (age range = 20-79 years) with no neurological, psychiatric, or cognitive disorders and estimated voxelwise MWF and fractional anisotropy (FA). We derived our regions of interest from the TBSS skeleton, including the whole WM, the late-myelinating prefrontal WM, and the genu of the corpus callosum. The cognitive assessment included the Virginia Cognitive Aging Battery and NIH Cognition Toolbox; confirmatory factor analysis yielded composite scores for memory, processing speed, and executive function. 

Age-myelin associations were negative linear (genu) and quadratic (whole and prefrontal WM), with the peak myelination at 46.9 years (whole WM) and 38.82 years (prefrontal WM). Age was negatively correlated with cognitive performance. Most importantly, regression analyses showed that myelin content in the prefrontal WM (β=0.14) and the genu (β=0.18) predicted memory performance, controlled for age, sex, and education. In contrast, although FA also showed negative associations with age and bivariate associations with cognition, none remained significant after correcting for age.

Our study provides the first direct evidence for the myelin hypothesis of cognitive decline using myelin-specific measures and extensive cognitive testing in a healthy aging sample. Our data suggests that information provided by FA may not tap into the functional aspects of WM despite its sensitivity to aging.