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Linda L. Chao, PhD; Norbert Schuff, PhD; Erin M. Clevenger, BA; Susanne G. Mueller, MD; Howard J. Rosen, MD; Maria L. Gorno-Tempini, MD, PhD; Joel H. Kramer, PhD; Bruce L. Miller, MD; Michael W. Weiner, MD

Arch Neurol. 2007;64(11):1619-1624.

Background  Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter (WM) alterations in this disease.

Objectives  To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degeneration—frontotemporal dementia (FTD) and semantic dementia—and to compare the patterns of WM atrophy with those of gray matter (GM) atrophy in these diseases.

Design  Structural MRIs were obtained from patients with FTD (n = 12) and semantic dementia (n = 13) and in cognitively healthy age-matched controls (n = 24). Regional GM and WM were classified automatically from high-resolution T1-, T2-, and proton density–weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates.

Results  Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD.

Conclusions  These results show that patients with frontotemporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders.

Author Affiliations: Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, California (Drs Chao, Schuff, Mueller, and Weiner, and Ms Clevenger); and Departments of Radiology (Drs Chao, Schuff, Mueller, and Weiner), Psychiatry (Drs Chao and Weiner), Neurology (Drs Rosen, Gorno-Tempini, Kramer, Miller, and Weiner), and Medicine (Dr Weiner), University of California, San Francisco.

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