Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study

Neurobiol Aging. 2019 Apr:76:115-124. doi: 10.1016/j.neurobiolaging.2018.12.017. Epub 2019 Jan 7.

Abstract

In genetic frontotemporal dementia, cross-sectional studies have identified profiles of presymptomatic neuroanatomical loss for C9orf72 repeat expansion, MAPT, and GRN mutations. In this study, we characterize longitudinal gray matter (GM) and white matter (WM) brain changes in presymptomatic frontotemporal dementia. We included healthy carriers of C9orf72 repeat expansion (n = 12), MAPT (n = 15), GRN (n = 33) mutations, and related noncarriers (n = 53), that underwent magnetic resonance imaging at baseline and 2-year follow-up. We analyzed cross-sectional baseline, follow-up, and longitudinal GM and WM changes using voxel-based morphometry and cortical thickness analysis in SPM and tract-based spatial statistics in FSL. Compared with noncarriers, C9orf72 repeat expansion carriers showed lower GM volume in the cerebellum and insula, and WM differences in the anterior thalamic radiation, at baseline and follow-up. MAPT mutation carriers showed emerging GM temporal lobe changes and longitudinal WM degeneration of the uncinate fasciculus. GRN mutation carriers did not show presymptomatic neurodegeneration. This study shows distinct presymptomatic cross-sectional and longitudinal patterns of GM and WM changes across C9orf72 repeat expansion, MAPT, and GRN mutation carriers compared with noncarriers.

Keywords: Diffusion tensor imaging; Frontotemporal dementia; Frontotemporal lobar degeneration; Hereditary dementia; Magnetic resonance imaging; Preclinical disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C9orf72 Protein / genetics
  • Cross-Sectional Studies
  • DNA Repeat Expansion / genetics
  • Diffusion Tensor Imaging*
  • Female
  • Frontotemporal Dementia / diagnostic imaging*
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / pathology
  • Gray Matter / diagnostic imaging*
  • Gray Matter / pathology*
  • Heterozygote
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation
  • Neuroimaging*
  • Progranulins / genetics
  • White Matter / diagnostic imaging*
  • White Matter / pathology*
  • tau Proteins / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • GRN protein, human
  • MAPT protein, human
  • Progranulins
  • tau Proteins