Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia

Abstract

Objective: To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA).

Methods: This was a case-control study where 16 subjects with bvFTD, 7 with PNFA, and 4 with SMD were identified and matched by age and gender to 19 controls. All subjects had 3-T head MRI with a DTI sequence with diffusion encoding in 21 directions. Gray matter mean diffusivity (MD) was assessed using a region-of-interest (ROI) and voxel-level approach, and voxel-based morphometry was used to assess patterns of gray matter loss. White matter tract diffusivity (fractional anisotropy and radial diffusivity) was assessed by placing ROIs on tracts of interest.

Results: In bvFTD, increased gray matter MD and gray matter loss were identified bilaterally throughout frontal and temporal lobes, with abnormal diffusivity observed in white matter tracts that connect to these regions. In SMD, gray matter loss and increased MD were identified predominantly in the left temporal lobe, with tract abnormalities observed in the inferior longitudinal fasciculus and uncinate fasciculus. In PNFA, gray matter loss and increased MD were observed in left inferior frontal lobe, insula, and supplemental motor area, with tract abnormalities observed in the superior longitudinal fasciculus.

Conclusions: The diffusivity of gray matter is increased in regions that are atrophic in frontotemporal dementia, suggesting disruption of the cytoarchitecture of remaining tissue. Furthermore, damage was identified in white matter tracts that interconnect these regions, supporting the hypothesis that these diseases involve different and specific brain networks.

Figure 1 Illustration of placement of fractional anisotropy regions of interest Fractional anisotropy color map from a control subject illustrating the placement of the white matter tract regions of interest. Regions of interest have been placed in the left hemisphere only. AC = anterior cingulate; ant = anterior; CST = corticospinal tract; GCC = genu of the corpus callosum; ILF = inferior longitudinal fasciculus; PC = posterior cingulate; post = posterior; SCC = splenium of the corpus callosum; SLF = superior longitudinal fasciculus; sup = superior; UNC = uncinate fasciculus.

Figure 2 Patterns of gray matter loss and mean diffusivity increase using statistical parametric mapping Three-dimensional renderings of the brain showing the patterns of gray matter loss (left) and patterns of mean diffusivity (MD) increase (right) in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA) groups compared with controls. Results are shown uncorrected for multiple comparisons at p < 0.001.

Figure 3 Box plots showing the distribution of fractional anisotropy values for the disease groups To aid comparison, fractional anisotropy (FA) values were centered at the region of interest (ROI)–specific control group mean (defined as zero on the horizontal axis) and thus can be interpreted as differences between each disease group and controls for each white matter tract ROI. The boxes indicate the 25th, 50th (median), and 75th percentiles of the distributions, whereas the horizontal lines extending from the boxes stop at the most extreme data points. AC = anterior cingulate; ant = anterior; bvFTD = behavioral variant frontotemporal dementia; CST = corticospinal tract; GCC = genu of the corpus callosum; ILF = inferior longitudinal fasciculus; PC = posterior cingulate; post = posterior; PNFA = progressive nonfluent aphasia; SCC = splenium of the corpus callosum; SLF = superior longitudinal fasciculus; SMD = semantic dementia; sup = superior; UNC = uncinate fasciculus. * p < 0.10, ** p < 0.05 vs controls based on false discovery rate–corrected analysis of covariance p value.