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.

Figure 1

Reconstructions of the white matter (WM) tracts in a reference healthy control superimposed on the single subject's fractional anisotropy images. The cingulum and the fornix (A) are the major WM connections passing through the medial temporal lobe. The uncinate and the inferior longitudinal fasciculi (B) connect the anterior temporal lobe with frontal and occipital cortices. The superior longitudinal and the inferior fronto‐occipital fasciculi (C) connect the frontal cortex with the occipital and parieto‐temporal lobes. The corpus callosum (D) is the major interhemispheric WM tract.

Figure 2

Illustration of the white matter (WM) tract probability maps obtained from reference healthy subjects. Probability maps are superimposed on (A) axial and (B) coronal sections of the fractional anisotropy atlas.

Figure 3

Boxplots showing the distribution of diffusion tensor MRI indices in patients with amnestic mild cognitive impairment, patients with Alzheimer's disease, and healthy controls. The boxes represent the interquartile ranges, which contain 50% of individual subjects' values. The whiskers are lines that extend from the box to the highest and lowest values, excluding outliers. A line across the box indicates the median value. Abbreviations: HC, healthy controls; aMCI, amnestic mild cognitive impairment; AD, Alzheimer's disease; FA, fractional anisotropy; MD, mean diffusivity; DA, axial diffusivity; DR, radial diffusivity; ILF, inferior longitudinal fasciculus; SLF, superior longitudinal fasciculus; IFO, inferior frontooccipital fasciculus. *P < 0.05 on General Linear Model test.

Figure 4

Scatterplot showing the significant relationships between axial diffusivity (DA) of the fornix and hippocampal volume in patients with amnestic mild cognitive impairment (empty circles) and Alzheimer's disease (filled circles).