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.