White matter microstructural damage in Alzheimer's disease at different ages of onset

White matter (WM) microstructural damage and its relationship with cortical abnormalities were explored in early-onset Alzheimer's disease (EOAD) compared with late-onset AD (LOAD) patients. Structural and diffusion tensor magnetic resonance images were obtained from 22 EOAD patients, 35 LOAD patients, and 40 healthy controls. Patterns of WM microstructural damage and cortical atrophy, as well as their relationships, were assessed using tract-based spatial statistics, tractography and voxel-based morphometry. Compared with LOAD, EOAD patients had a more severe and distributed pattern of WM microstructural damage, in particular in the posterior fibers of cingulum and corpus callosum. In both groups with Alzheimer's disease, but especially in LOAD patients, correlations between cingulum and corpus callosum fractional anisotropy and parietal, temporal, and frontal cortical volumes were found. In conclusion, WM microstructural damage is more severe in EOAD compared with LOAD patients. Such damage follows different patterns of topographical distribution in the 2 patient groups.