Pattern of diffusion tensor MRI (DTI) alterations were investigated in pathologically-staged Alzheimer's disease (AD) patients (n = 46). Patients with antemortem DTI studies and a range of AD pathology at autopsy were included. Patients with a high neurofibrillary tangle (NFT) stage (Braak IV–VI) had significantly elevated mean diffusivity (MD) in the crus of fornix and ventral cingulum tracts, precuneus, and entorhinal white matter on voxel-based analysis after adjusting for age and time from MRI to death (p < 0.001). Higher MD and lower fractional anisotropy in the ventral cingulum tract, entorhinal, and precuneus white matter was associated with higher Braak NFT stage and clinical disease severity. There were no MD and fractional anisotropy differences among the low (none and sparse) and high (moderate and frequent) β-amyloid neuritic plaque groups. The NFT pathology of AD is associated with DTI alterations involving the medial temporal limbic connections and medial parietal white matter. This pattern of diffusion abnormalities is also associated with clinical disease severity.
