Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia

Arch Neurol. 2008 Feb;65(2):249-55. doi: 10.1001/archneurol.2007.38.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrophy / diagnosis
  • Brain Stem / pathology
  • Case-Control Studies
  • Cohort Studies
  • Corpus Callosum / pathology
  • Dementia / pathology*
  • Female
  • Frontal Lobe / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Limbic System / pathology
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Severity of Illness Index
  • Social Behavior Disorders / etiology
  • Social Behavior Disorders / pathology*