Ventromedial-frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer's disease

Hum Brain Mapp. 2014 Feb;35(2):616-26. doi: 10.1002/hbm.22200. Epub 2012 Nov 5.


Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non-fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel-based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight.

Keywords: Alzheimer's disease; frontopolar cortex; frontotemporal dementia; insight; self-evaluation; ventromedial frontal cortex; voxel-based morphometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology
  • Analysis of Variance
  • Atrophy / etiology
  • Atrophy / pathology
  • Brain Mapping*
  • Cohort Studies
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Frontotemporal Dementia / complications
  • Frontotemporal Dementia / pathology*
  • Frontotemporal Dementia / psychology
  • Humans
  • Interpersonal Relations
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prefrontal Cortex / pathology*
  • Psychiatric Status Rating Scales
  • Surveys and Questionnaires