White Matter Damage in Alzheimer Disease and Its Relationship to Gray Matter Atrophy

Abstract

To explore the regional patterns of white matter (WM) tract damage in (a) patients with probable Alzheimer disease (AD) and (b) patients with amnestic mild cognitive impairment (aMCI) and at least one abnormal biomarker and to investigate whether WM damage is related to gray matter (GM) atrophy. This study was approved by the institutional review board, and written informed consent was obtained from each participant. Twenty-three patients with AD, 15 patients with aMCI, and 15 healthy control subjects underwent diffusion tensor magnetic resonance imaging. WM tract damage was investigated by using tract-based spatial statistics, and GM atrophy was measured by using voxel-based morphometry. Compared with control subjects, patients with AD had an increase in mean diffusivity in all major WM tracts studied, including the limbic, cortico-cortical, interhemispheric, and corticospinal tracts. Conversely, fractional anisotropy decreased only in the parahippocampal tract, fornix, and small, inferior parietal regions. In addition, patients with AD showed a widespread increase in axial and radial diffusivity compared with control subjects. Patients with aMCI showed an increase in axial diffusivity only in tracts projecting to the frontal cortex and splenium of the corpus callosum. Significant and anatomically congruent correlations between WM changes and regional GM atrophy were found in patients with AD. Conversely, damage to most WM tracts in patients with aMCI did not correlate with GM atrophy. In AD, the observed patterns of WM abnormalities may reflect the advanced phase of a secondary degenerative process and an association, especially in the early phases of the disease, with primary WM tract damage over and above GM abnormalities.