Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Neurology. 2019 Oct 29;93(18):e1699-e1706. doi: 10.1212/WNL.0000000000008386. Epub 2019 Oct 2.


Objective: To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.

Methods: Participants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers.

Results: A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings.

Conclusions: Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C9orf72 Protein / genetics
  • Cerebral Ventricles / diagnostic imaging*
  • Cerebral Ventricles / pathology
  • Female
  • Frontotemporal Dementia / diagnostic imaging*
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / pathology
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Prodromal Symptoms*
  • Progranulins / genetics
  • tau Proteins / genetics


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