Neurite density is reduced in the presymptomatic phase of C9orf72 disease. Issue 4 (24th October 2018)

• Record Type: Journal Article
• Authors: Wen, Junhao; Zhang, Hui; Alexander, Daniel C; Durrleman, Stanley; Routier, Alexandre; Rinaldi, Daisy; Houot, Marion; Couratier, Philippe; Hannequin, Didier; Pasquier, Florence; Zhang, Jiaying; Colliot, Olivier; Le Ber, Isabelle; Bertrand, Anne
• Other Names: author non-byline.; Benchetrit Eve author non-byline.; Bertin Hugo author non-byline.; Bertrand Anne author non-byline.; Bissery Anne Bissery author non-byline.; Bombois Stéphanie author non-byline.; Boncoeur Marie-Paule author non-byline.; Cassagnaud Pascaline author non-byline.; Chastan Mathieu author non-byline.; Chen Yaohua author non-byline.; Chupin Marie author non-byline.; Colliot Olivier author non-byline.; Couratier Philippe author non-byline.; Delbeucq Xavier author non-byline.; Deramecourt Vincent author non-byline.; Delmaire Christine author non-byline.; Gerardin Emmanuel author non-byline.; Hossein-Foucher Claude author non-byline.; Dubois Bruno author non-byline.; Habert Marie-Odile author non-byline.; Hannequin Didier author non-byline.; Lautrette Géraldine author non-byline.; Lebouvier Thibaud author non-byline.; Le Ber Isabelle author non-byline.; Lehéricy Stéphane author non-byline.; Le Toullec Benjamin author non-byline.; Levy Richard author non-byline.; Martinaud Olivier author non-byline.; Martineau Kelly author non-byline.; Mackowiak Marie-Anne author non-byline.; Monteil Jacques author non-byline.; Pasquier Florence author non-byline.; Petyt Grégory author non-byline.; Pradat Pierre-François author non-byline.; Oya Assi-Hervé author non-byline.; Rinaldi Daisy author non-byline.; Rollin-Sillaire Adeline author non-byline.; Salachas François author non-byline.; Sayah Sabrina author non-byline.; Wallon David author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90:Issue 4(2019)
• Page Start: 387
• Page End: 394
• Publication Date: 2018-10-24
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2018-318994
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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 .