IC-P-068: Diffusion tensor imaging of normal appearing white matter in MCI and AD

Abstract

Structural magnetic resonance imaging (MRI) studies on mild cognitive impairment (MCI) and Alzheimer's disease (AD) have largely focused on the brain's cortical gray matter. However, cellular degeneration in cortical structures is usually accompanied by concomitant degeneration of axonal processes from these dying neurons. Pathoanatomical and imaging studies have confirmed both macroscopic and microscopic white matter changes in patients with AD. We propose that microstructural changes in subcortical brain regions should also be detectable in MCI. To examine the microstructural integrity of subcortical white mater in subjects with amnestic MCI and mild AD using diffusion tensor imaging (DTI). Elderly subjects with normal cognition (n=5), MCI (n=6) and mild AD (n=4) were recruited from our Alzheimer's Disease Research Center. Petersen criteria were used to diagnose amnestic MCI, and NINCDS–ADRDA criteria to diagnose AD. Normal appearing white matter (NAWM) was defined by normal signal intensity on standard T1–weighted, T2–weighted and FLAIR images. DTI images were acquired using a single shot, pulsed gradient, echo planar imaging protocol with twelve non–collinear gradient directions. Fractional anisotropy (FA), axial diffusivity (DA) and radial diffusivity (DR) of NAWM regions in the frontal, temporal, parietal and occipital lobes were measured and compared across the three groups using ANOVA with post–hoc Scheffe tests. Both AD and MCI subjects demonstrated significantly lower FA in frontal and temporal NAWM compared with normal control subjects (AD/MCI/normal = 0.28/0.28/0.35 in frontal NAWM, F=6.61, df =2, p<0.01; AD/MCI/normal = 0.41/0.44/0.52 in temporal NAWM, F=14.2, df =2, p<0.001). Radial diffusivity (DR) was significantly greater in AD and MCI subjects compared to normal controls in parietal NAWM (AD/MCI/normal = 0.62/0.60/0.56, F=11.9, df=2, p<0.001). Even in NAWM, we found evidence for microstructural changes in AD and MCI. These changes were present in brain regions serving higher cortical functions (frontal, temporal and parietal lobes), but not in regions serving primary functions (occipital lobe), and are consistent with a hypothesized loss of axonal processes in affected regions.