The Pattern of Diffusion Parameter Changes in Alzheimer's Disease, Identified by Means of Linked Independent Component Analysis

Several recent studies have indicated that white matter is affected in Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white matter microstructure can be examined in vivo, and might offer a possibility for the identification of the pattern of white matter disintegration in AD. In the current analysis, we made use of a novel model-free analysis approach of linked independent component analysis to identify a motif of diffusion parameter alterations exemplifying AD. Analysis of the diffusion data of 16 AD patients and 17 age-matched healthy subjects revealed six independent components, two of which demonstrated differences between the patients and controls. Component #0 was dominated by axial diffusivity, but significant alterations in fractional anisotropy and mean and radial diffusivity were also detected. Alterations were found in regions of crossing of major white matter pathways, such as forceps, corona radiata, and superior longitudinal fascicle, as well as medio-temporal white matter. These results lend support to the coexistence of white matter disintegration of the late myelinating associating fibers and wallerian degeneration-related disintegration, in accordance with the retrogenesis and wallerian degeneration hypothesis.