Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study

Neurobiol Aging. 2018 Feb:62:191-196. doi: 10.1016/j.neurobiolaging.2017.10.008. Epub 2017 Oct 19.

Abstract

Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease.

Keywords: Atrophy; Frontotemporal dementia; Magnetic resonance imaging; Preclinical dementia; Voxel-based morphometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atrophy
  • C9orf72 Protein / genetics
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / pathology*
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology*
  • Heterozygote
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Organ Size
  • Progranulins
  • tau Proteins / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Progranulins
  • tau Proteins