Hippocampal Subfield Volumetry: Differential Pattern of Atrophy in Different Forms of Genetic Frontotemporal Dementia

J Alzheimers Dis. 2018;64(2):497-504. doi: 10.3233/JAD-180195.

Abstract

Background: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder, with a strong genetic component. Previous research has shown that medial temporal lobe atrophy is a common feature of FTD. However, no study has so far investigated the differential vulnerability of the hippocampal subfields in FTD.

Objectives: We aimed to investigate hippocampal subfield volumes in genetic FTD.

Methods: We in6/2/2018vestigated hippocampal subfield volumes in a cohort of 75 patients with genetic FTD (age: mean (standard deviation) 59.3 (7.7) years; disease duration: 5.1 (3.4) years; 29 with MAPT, 28 with C9orf72, and 18 with GRN mutations) compared with 97 age-matched controls (age: 62.1 (11.1) years). We performed a segmentation of their volumetric T1-weighted MRI scans to extract hippocampal subfields volumes. Left and right volumes were summed and corrected for total intracranial volumes.

Results: All three groups had smaller hippocampi than controls. The MAPT group had the most atrophic hippocampi, with the subfields showing the largest difference from controls being CA1-4 (24-27%, p < 0.0005). For C9orf72, the CA4, CA1, and dentate gyrus regions (8-11%, p < 0.0005), and for GRN the presubiculum and subiculum (10-14%, p < 0.0005) showed the largest differences from controls.

Conclusions: The hippocampus was affected in all mutation types but a different pattern of subfield involvement was found in the three genetic groups, consistent with differential cortical-subcortical network vulnerability.

Keywords: Genetic frontotemporal dementia; hippocampal subfields; magnetic resonance imaging; volumetry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrophy / etiology
  • C9orf72 Protein / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / complications
  • Frontotemporal Dementia / diagnostic imaging*
  • Frontotemporal Dementia / genetics*
  • Hippocampus / diagnostic imaging*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Progranulins / genetics*
  • tau Proteins / genetics*

Substances

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