Corpus Callosal Atrophy in Premanifest and Early Huntington's Disease

Article type: Research Article

Authors: Crawford, Helen E. | Hobbs, Nicola Z. | Keogh, Ruth | Langbehn, Douglas R. | Frost, Chris | Johnson, Hans | Landwehrmeyer, Bernhard | Reilmann, Ralf | Craufurd, David | Stout, Julie C. | Durr, Alexandra | Leavitt, Blair R. | Roos, Raymund A.C. | Tabrizi, Sarah J. | Scahill, Rachael I. | the TRACK-HD Investigators

Affiliations: UCL Institute of Neurology, University College London, UK | Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK | Departments of Psychiatry and Biostatistics (Secondary), University of Iowa, Iowa City, IA, USA | Department of Psychiatry, University of Iowa, Iowa City, IA, USA | Department of Neurology, Ulm University, Ulm, Germany | Department of Neurology, University of Münster, Münster, Germany | Institute of Human Development, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK and Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK | School of Psychology and Psychiatry, Monash University, VIC, Australia | Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France | Centre for Molecular Medicine & Therapeutics, Dept. of Medical Genetics, University of British Columbia, Vancouver, BC, Canada | Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

Note: [] Correspondence to: Rachael I. Scahill; TRACK-HD, Box 104, Institute of Neurology, University College London, Department of Neurodegenerative Disease, Queen Square, London, WC1N 3BG, UK. Tel.: +44 207 242 0038; Fax: +44 207 611 0129; E-mail: [email protected]

Abstract: Background: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. Objectives: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. Methods: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. Results: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. Conclusions: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.

Keywords: Huntington's disease, MRI, corpus callosum, atrophy

DOI: 10.3233/JHD-130077

Journal: Journal of Huntington's Disease, vol. 2, no. 4, pp. 517-526, 2013