Objective To investigate cognitive inhibition in presymptomatic C9orf72 mutation carriers (C9+) and its associated neuroanatomical correlates.
Methods Thirty-eight presymptomatic C9orf72 mutation carriers (C9+, mean age 38.2±8.0 years) and 22 C9− controls from the PREV-DEMALS cohort were included in this study. They underwent a cognitive inhibition assessment with the Hayling Sentence Completion Test (HSCT; time to completion (part B−part A); error score in part B) as well as a 3D MRI.
Results C9+ individuals younger than 40 years had higher error scores (part B) but equivalent HSCT time to completion (part B−part A) compared to C9− individuals. C9+ individuals older than 40 years had both higher error scores and longer time to completion. HSCT time to completion significantly predicted the proximity to estimated clinical conversion from presymptomatic to symptomatic phase in C9+ individuals (based on the average age at onset of affected relatives in the family). Anatomically, we found that HSCT time to completion was associated with the integrity of the cerebellum.
Conclusion The HSCT represents a good marker of cognitive inhibition impairments in C9+ and of proximity to clinical conversion. This study also highlights the key role of the cerebellum in cognitive inhibition.
- C9orf72 mutation
- cognitive inhibition
- hayling sentence completion test
- voxel-based morphometry
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ILB and RM contributed equally.
Contributors Study supervision: ILB, RM. Study conception and design: MM, RM, ILB. Data acquisition: SS, DS, DR, BLT, ILB, AF, AC, PC, MC, DH, CA-G, FP, XD. Analysis and interpretation of data: MM, RM, ILB, SS, BB, OC, AB. Drafting the manuscript: MM, RM, ILB. Obtaining funding: ILB, OC, AB. All authors critically revised the manuscript for its intellectual content.
Funding This study was funded by grant ANR/DGOS PRTS 2015-2019 PREV-DEMALS from the Assistance Publique–Hôpitaux de Paris (Dr Le Ber) and by grant ANR-10-IAIHU-06 from the Agence Nationale de la Recherche. The study was conducted with the support of the Centre d’Investigation Clinique and the Centre pour l’Acquisition et le Traitement des Images platform. Raffaella Migliaccio is supported by France Alzheimer and Philippe Chatrier Foundations, and by Rosita Gomez association. Raffaella Migliaccio, Richard Levy and Bénédicte Batrancourt are supported by Fondation pour la Recherche Medicale. Maxime Montembeault is supported by postdoctoral fellowships from the Canadian Institutes of Health Research (CIHR) and Fonds de Recherche du Québec en Santé (FRQS).
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval This study was approved by the Comité de Protection des Personnes Ile de France VI of the Hôpital Pitié-Salpetrière.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request (email@example.com).