Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers

Neuroimage. 2009 Apr 15;45(3):713-21. doi: 10.1016/j.neuroimage.2008.12.024. Epub 2008 Dec 25.

Abstract

Frontotemporal dementia constitutes the third most prevalent neurodegenerative disease with dementia. We compared cortical structural changes in nine presymptomatic CHMP2B frontotemporal dementia mutation positive individuals with seven mutation negative family members. Using serial MRI scans with a mean interval of 16 months and surface based cortical segmentation we measured cortical thickness and volume, and quantified atrophy rates. Cortical thickness and atrophy rates were averaged within major lobes and focal effects were determined by parametric statistical maps. The volumetric atrophy rates in the presymptomatic CHMP2B mutation carriers were statistically significant, though of a lower magnitude than those previously reported in patients of other types of frontotemporal dementia. Cortical thickness measurements revealed cortical thinning in mutation carriers bilaterally in the frontal and occipital lobes, and in the left temporal lobe. Results indicated that cortical thickness has a higher sensitivity for detecting small changes than whole-brain volumetric measures. Comparing mutation carriers with non-carriers revealed increased atrophy rates in mutation carriers bilaterally in the inferio-temporal cortex, the superior frontal cortex, and the insular cortex. These findings indicated impairment of regions involved in both behaviour and language. The symptoms previously reported in clinical CHMP2B frontotemporal dementia patients are associated with the anatomically affected regions here found in the presymptomatic mutation carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrophy
  • Cerebral Cortex / pathology*
  • Dementia / genetics*
  • Dementia / pathology*
  • Endosomal Sorting Complexes Required for Transport
  • Family
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*

Substances

  • CHMP2B protein, human
  • Endosomal Sorting Complexes Required for Transport
  • Nerve Tissue Proteins