Section: New Results

Neurite density is reduced in the presymptomatic phase of C9orf72 disease

Participants : Junhao Wen, Hui Zhang, Daniel Alexander, Stanley Durrleman, Olivier Colliot, Isabelle Le Ber, Anne Bertrand [Correspondant] .

In this study, we aimed to assess the added value of neurite orientation dispersion and density imaging (NODDI) compared to conventional DTI and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation. The PREV-DEMALS study is a prospective, multicenter, observational study of first-degree relatives of individuals carrying the C9orf72 mutation. Sixty-seven participants (38 presymptomatic C9orf72 mutation carriers [C9+], 29 non carriers [C9-]) were included in the present cross-sectional study. Each participant underwent one single-shell, multi-shell diffusion MRI and 3DT1 MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, gray matter volume and free water fraction between C9+ and C9- individuals were assessed using linear mixed-effects models. 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 gray matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy. In conclusion, NODDI provides higher sensitivity and greater tissue-specificity compared to conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as biomarker of the preclinical phase.

More details in [34].