Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia

Background: Two major clinical variants of frontotemporal dementia (FTD) have been described: frontal variant (fvFTD) and temporal variant (tvFTD). Objective: To analyze white matter (WM) and gray matter (GM) tissue organization in patients with fvFTD and tvFTD by means of diffusion tensor imaging and voxel-based morphometry, and the correlations with neuropsychological and behavioral variables. Design and Setting: Frontotemporal dementia clinic based cohort and structural magnetic resonance imaging acquisition for voxel-based morphometry and diffusion tensor imaging measurements. Abnormalities were detected by a comparison with healthy control subjects. These variables were also correlated with clinical scores. Patients: Thirty-six patients (28 with fvFTD and 8 with tvFTD) in early disease stage and 23 healthy controls who underwent standardized clinical and neuropsychological evaluation and magnetic resonance imaging. Interventions: Diffusion tensor imaging and voxel-based morphometry. Main Outcome Measures: Neuroimaging analyses resulted in localized GM atrophy and reductions of white matter densities; the latter correlated with behavioral scores. Results: Voxel-based morphometry analysis showed separate patterns of GM atrophy in the 2 groups. Diffusion tensor imaging showed different WM reduction patterns in patients with fvFTD and tvFTD. The fvFTD group showed a selective WM reduction in the superior longitudinal fasciculus, interconnecting the frontal and occipital and the temporal and parietal regions. Conversely, patients with tvFTD were characterized by WM reductions in the inferior longitudinal fasciculus, which affected the connections between anterior temporal and frontal regions. The WM reductions in fvFTD paralleled both behavioral disturbances measured by Frontal Behavioral Inventory and neuropsychological deficits affecting frontal functions. Conclusions: The fvFTD and tvFTD variants are associated not only with selective local GM reductions but also with significant WM damage in early disease phase. The different WM patterns contribute to the different clinical syndromes in FTD and could be responsible for the further progression of atrophy in the later disease stages.