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William W. Seeley, MD; Richard Crawford, BS; Katya Rascovsky, PhD; Joel H. Kramer, PsyD; Michael Weiner, MD; Bruce L. Miller, MD; Maria Luisa Gorno-Tempini, MD, PhD

Arch Neurol. 2008;65(2):249-255.

Background  Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear.

Objective  To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex.

Design  A bvFTD cohort study.

Setting  University hospital dementia clinic.

Participants  Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n = 15), 1 (n = 15), or 2 to 3 (n = 15) age and sex matched to each other and to 45 healthy controls.

Main Outcome Measures  Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls.

Results  Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. A CDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers.

Conclusions  Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury.

Author Affiliations: Department of Neurology and Memory and Aging Center (Drs Seeley, Rascovsky, Kramer, Miller, and Gorno-Tempini and Mr Crawford) and Department of Radiology and San Francisco Veterans Affairs Hospital Magnetic Resonance Imaging Unit (Dr Weiner), University of California at San Francisco.

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