Assessment of white matter tract damage in mild cognitive impairment and Alzheimer's disease

Abstract

Diffusion tensor MRI-based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico-cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto-occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas-based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto-occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico-cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico-cortical association pathways in aMCI and AD patients.

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

“…Although the FA has been widely used as a measure to assess the integrity of brain connections (Kiuchi et al, 2009;Pievani et al, 2010;Teipel et al, 2010), we did not observe any trends toward significance in this parameter in our study.…”

“…Hence we observed the highest trend toward significance in an increase of radial diffusivity, but no change in FA. Indeed the significant increase in radial diffusivity in the fornix in MCI and Alzheimer's disease patients compared to healthy controls found by Pievani et al (2010) may have been caused by degeneration of the cholinergic axons. In addition, significant changes in the integrity of tracts originating in the basal forebrain have been observed in Alzheimer's disease patients using tract-based spatial statistics, where measures of tract integrity were determined based on the FA parameter (Teipel et al, 2010).…”

“…Diffusion MRI (dMRI) is a technique that can be used to analyze differences in structural integrity and brain connectivity, and has been successfully employed to detect differences between Alzheimer's patients and healthy control subjects (Kiuchi et al, 2009;Pievani et al, 2010;Teipel et al, 2010). dMRI measures water diffusion within a tissue, with common dMRI measures including fractional anisotropy (FA), a measure of the degree of diffusion anisotropy where a value of zero means that diffusion is unrestricted (or equally restricted) and a value of one means that diffusion only occurs along one axis and is fully restricted in all other directions, mean diffusivity, a measure describing the extent of free diffusion without assuming a particular direction, axial diffusivity (AD; also known as parallel diffusivity), a measure of the extent of water moving along the primary axis of diffusion, and radial diffusivity (RD; also known as perpendicular diffusivity), a measure of water movement along the minor axes perpendicular to the primary axis.…”

Assessment of White Matter Tract Damage in Patients with Amyotrophic Lateral Sclerosis: A Diffusion Tensor MR Imaging Tractography Study: Fig 1.

“…Regions of significant increase of axial D in the major corticocortical association tracts have been recently observed with normal aging 50 and in other neurodegenerative diseases, such as Alzheimer disease. 51,52 In a previous voxel-based DTI study of the same patients with ALS, 17 we found clusters of extramotor increase of MD in the frontal, temporal, and occipital lobes, which only partially overlapped the uncinate fasciculus. One explanation for this would be the different spatial resolution (tract-versus voxel-based), because the presence of microstructural damage in a small region may not have affected the average DTI metrics of the WM tract.…”

Individual Classification of Mild Cognitive Impairment Subtypes by Support Vector Machine Analysis of White Matter DTI

“…Suprathreshold voxels were enlarged by using TBSS fill (part of FSL) for illustrative purposes. investigations on the different diffusion parameters in normal aging, MCI, and AD 28,[74][75][76][77] provided inconsistent data with respect to the regional differences in the distribution of significant changes in FA, longitudinal diffusivity, radial diffusivity, and mean diffusivity. For example, in the above mentioned study of subjects with MCI and AD, FA was more closely related to the cognitive profile than longitudinal diffusivity or radial diffusivity.…”