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Barbara Borroni, MD; Simona Maria Brambati, PhD; Chiara Agosti, MD; Stefano Gipponi, MD; Giuseppe Bellelli, MD; Roberto Gasparotti, MD; Valentina Garibotto, MD; Monica Di Luca, PhD; Paola Scifo, PhD; Daniela Perani, MD; Alessandro Padovani, MD, PhD

Arch Neurol. 2007;64(2):246-251.

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.

Author Affiliations: Department of Medical Sciences, Center for Brain Aging and Neurodegenerative Disorders (Drs Borroni, Agosti, Gipponi, and Padovani), and Neuroradiology Unit (Dr Gasparotti), University of Brescia, Brescia, Italy; Memory Aging Center, Department of Neurology, University of California, San Francisco (Dr Brambati); Vita-Salute San Raffaele University, Milan, Italy (Drs Brambati, Garibotto, and Perani); Scientific Institute San Raffaele, Milan (Drs Brambati, Garibotto, Scifo, and Perani); IBFM-CNR, Milan (Drs Brambati, Garibotto, and Perani); "Ancelle della Carità" Hospital, Cremona, Italy (Dr Bellelli); and Department of Pharmacological Sciences and Centre of Excellence of Neurodegenerative Disorders, University of Milan, Milan (Dr Di Luca).

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