 Els Fieremans |
 Andreana Benitez |
Our research focuses on the study of degeneration in brain white matter, which consists primarily of myelinated axons that connect gray matter regions, using MRI. Although Alzheimer disease (AD) is typically considered a gray matter disease, postmortem studies have provided evidence of pathological changes in white matter occurring early in the course of AD, while in vivo MRI studies report correlations between white matter damage and disease severity.
In this study, we compare the white matter integrity in subjects with mild cognitive impairment (MCI) and AD with age-matched healthy controls, using diffusion MRI, a powerful method that is sensitive to microstructural loss preceding atrophy. White matter integrity is assessed using diffusional kurtosis imaging (DKI), a diffusion method that is clinically feasible and goes beyond DTI. We recently provided a biophysical interpretation of the DKI signal in terms of specific white matter tract integrity metrics. These include the axonal water fraction, a marker for axonal loss; and the radial and axial extra-axonal diffusivities, markers for demyelination and other extra-axonal changes, including inflammation.
When investigating these white matter tract integrity metrics in a cross-sectional study that simulates the course of AD, we found that these novel markers were able to both detect and differentiate specific tissue changes in MCI and AD. Interestingly, our findings suggest that widespread breakdown in myelin integrity occurs first in the transition from normal aging to the amnestic mild cognitive impairment (aMCI) stage (AUC=0.95, P<.001), whereas a loss in axonal density occurs later in the disease from aMCI to AD (AUC=0.84, P=.01). Regional analyses of these