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Publication Detail
Neurite density is reduced in the presymptomatic phase of C9orf72 disease
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Wen J, Zhang H, Alexander DC, Durrleman S, Routier A, Rinaldi D, Houot M, Couratier P, Hannequin D, Pasquier F, Zhang J, Colliot O, Le Ber I, Bertrand A
  • Publication date:
  • Journal:
    Journal of Neurology, Neurosurgery and Psychiatry
  • Status:
  • Print ISSN:
© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ. Objective: To assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation. Methods: The PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis) study is a prospective, multicentre, observational study of first-degree relatives of individuals carrying the C9orf72 mutation. Sixty-seven participants (38 presymptomatic C9orf72 mutation carriers (C9+) and 29 non-carriers (C9')) were included in the present cross-sectional study. Each participant underwent one single-shell, multishell diffusion MRI and three-dimensional T1-weighted MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, grey matter volume and free water fraction between C9+ and C9' individuals were assessed using linear mixed-effects models. Results: Compared with C9', C9+ demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. Effect size was significantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a significantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy. Conclusions: NODDI provides higher sensitivity and greater tissue specificity compared with conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase. Trial registration number: NCT02590276.
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