Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment

Structural magnetic resonance imaging (MRI) studies of Alzheimer's disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases directional diffusion (fractional anisotropy: FA) damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI.