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. 2009 Sep;132(Pt 9):2579-92.
doi: 10.1093/brain/awp071. Epub 2009 May 12.

White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI

Yu Zhang  1 , Norbert Schuff, An-Tao Du, Howard J Rosen, Joel H Kramer, Maria Luisa Gorno-Tempini, Bruce L Miller, Michael W Weiner
Affiliations

White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI

Yu Zhang et al. Brain. 2009 Sep.

Abstract

Frontotemporal dementia (FTD) and Alzheimer's disease are sometimes difficult to differentiate clinically because of overlapping symptoms. Using diffusion tensor imaging (DTI) measurements of fractional anisotropy (FA) can be useful in distinguishing the different patterns of white matter degradation between the two dementias. In this study, we performed MRI scans in a 4 Tesla MRI machine including T1-weighted structural images and diffusion tensor images in 18 patients with FTD, 18 patients with Alzheimer's disease and 19 cognitively normal (CN) controls. FA was measured selectively in specific fibre tracts (including corpus callosum, cingulum, uncinate and corticospinal tracts) as well as globally in a voxel-by-voxel analysis. Patients with FTD were associated with reductions of FA in frontal and temporal regions including the anterior corpus callosum (P < 0.001), bilateral anterior (left P < 0.001; right P = 0.005), descending (left P < 0.001; right P = 0.003) cingulum tracts, and uncinate tracts (left P < 0.001; right P = 0.005), compared to controls. Patients with Alzheimer's disease were associated with reductions of FA in parietal, temporal and frontal regions including the left anterior (P = 0.003) and posterior (P = 0.002) cingulum tracts, bilateral descending cingulum tracts (P < 0.001) and left uncinate tracts (P < 0.001) compared to controls. When compared with Alzheimer's disease, FTD was associated with greater reductions of FA in frontal brain regions, whereas no region in Alzheimer's disease showed greater reductions of FA when compared to FTD. In conclusion, the regional patterns of anisotropy reduction in FTD and Alzheimer's disease compared to controls suggest a characteristic distribution of white matter degradation in each disease. Moreover, the white matter degradation seems to be more prominent in FTD than in Alzheimer's disease. Taken together, the results suggest that white matter degradation measured with DTI may improve the diagnostic differentiation between FTD and Alzheimer's disease.

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Figures

Figure 1
Figure 1
Placement of Seeds and Targets for TOI analysis: (A) To define the corticospinal tract, the Seed (red colour) was drawn on axial slice on the cerebral peduncle at the level of the decussation of the superior cerebellar peduncle; the Target (green colour) was placed on an axial slice on the precentral gyrus (primary motor cortex), anterior to the central sulcus. (B) To define the upper part of cingulum fibres, Seed (red) and Target (green) were placed on the anterior and posterior cingulum areas on the same coronal slice level as the genu and splenium of the corpus collosum, respectively. To define the descending part of cingulum, the Seed (red) and Target (green) were placed as shown in the figure. (C) The definition of the callosal fibre required only a single Seed (red) on a mid-sagittal slice. (D) To define the uncinate fascicules, the Seed (red) and Target (green) were positioned on a coronal slice on the most posterior slice where the frontal and temporal lobes appear separated.
Figure 2
Figure 2
Illustration of fibre tracts of the corpus callosum (CC), cingulum (Cg), uncinate (Unc) and the corticospinal tract (CST) from a single subject superimposed on a 3-dimensional FA image.
Figure 3
Figure 3
Illustration of location and coverage of TOI: anterior corpus callosum (a.CC), posterior corpus callosum (p.CC), anterior cingulum (a.Cg), posterior cingulum (p.Cg), descending cingulum (d.Cg), uncinate tracts (Unc) and corticospinal tracts (CST).
Figure 4
Figure 4
Rendered display of DTI changes (A) reduced FA (warm colours); (B) increased Dra (cool colours); (C) increased Dax (cool colours) in FTD or Alzheimer's disease compared with cognitively normal subjects, as well as direct comparisons between FTD and Alzheimer's disease.
Figure 5
Figure 5
Coronal view of the regional FA reductions between groups in anterior brain: the top row indicates regions of the tracts of interest (TOIs) analysis for comparison with the voxel-wise analyses in the rows below. The second row (FTD1-weighted brain template. The areas with significantly decreased FA values are marked in warm colours with threshold PFDR = 0.05.
Figure 6
Figure 6
Coronal view of the regional FA reductions in the posterior brain comparing between groups: the top row indicates regions of the tracts of interest (TOIs) analysis for comparison with the voxel-wise analyses in the rows below. The second row (FTD1-weighted brain template. The areas with significantly decreased FA values are marked in warm colours with threshold PFDR = 0.05.
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