Journal article
H01 Significant biological and clinical change detected over 1 year in premanifest and early stage Huntington's disease in the TRACK-HD study
Journal of neurology, neurosurgery and psychiatry, Vol.81(Suppl 1), pp.A33-A33
09/2010
DOI: 10.1136/jnnp.2010.222653.1
Abstract
Background/aims TRACK-HD is a multinational prospective, observational study of Huntington's disease (HD) that aims to examine longitudinal change in premanifest carriers of the mutant HTT gene and subjects with early stage disease (Tabrizi et al. Lancet Neurology 2009). New data from the first follow-up assessment are reported here, and build on previous findings from baseline 3T MRI and novel clinical, cognitive, quantitative motor, oculomotor and neuropsychiatric assessments. Of 366 subjects enrolled at baseline, 345 (115 controls, 116 premanifest (preHD) and 114 early HD) completed 12 months of follow-up. Statistical analysis was performed to assess annualised change in all modalities. Methods/techniques Annualised rates of global and regional atrophy were higher in both the pre- and early HD groups than in controls (p≤0.007). Whole brain atrophy rates were 0.3%, 0.5% and 0.9%, and caudate atrophy rates 0.6%, 2.0% and 3.5%, in controls, pre and early HD, respectively, over 1 year. Whole brain image analysis techniques also revealed striking cortical and subcortical grey and white matter atrophy over just 1 year even in subjects furthest from predicted disease onset. Quantitative imaging showed significant associations with disease burden and total functional capacity, a widely used clinical measure of disease severity. Cognitive deterioration was detectable in both HD groups. However, rates of decline in cognitive, quantitative motor and oculomotor tasks were greater after onset of motor signs. Results/outcome HD is characterised by a long premanifest state, slow progression and a disease course of around 20 years. After 1 year, we have identified robust change in a range of measures across modalities in both premanifest and early stage HD. Quantitative imaging showed the greatest differentiation across the spectrum of the disease and a number of functional measures of decline were sensitive in early HD with cognitive impairment also detectable in the pre-HD group. Conclusions TRACK-HD is the first multi-site study to report whole brain, regional and subcortical atrophy in premanifest subjects many years from predicted disease onset using 3T MR imaging; and demonstrates the feasibility of obtaining quantifiable endpoints which show robust change over just 1 year thus showing potential as endpoints for future therapeutic trials.
Details
- Title: Subtitle
- H01 Significant biological and clinical change detected over 1 year in premanifest and early stage Huntington's disease in the TRACK-HD study
- Creators
- S J Tabrizi - UCL Institute of Neurology, University College London, London, UKA Dürr - Department of Genetics and Cytogenetics and INSERM UMR S, APHP Hôpital de la Salpêtrière, Paris, FranceR A C Roos - Department of Neurology, Leiden University Medical Centre, Leiden, The NetherlandsB R Leavitt - Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, CanadaR Jones - London School of Hygiene and Tropical Medicine, London, UKG B Landwehrmeyer - Department of Neurology, Ulm University, Ulm, GermanyH Johnson - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USAS L Hicks - Department of Clinical Neurology, University of Oxford, Oxford, UKC Kennard - Department of Clinical Neurology, University of Oxford, Oxford, UKR Reilmann - Department of Neurology, University of Münster, Münster, GermanyD Craufurd - Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester, UKH D Rosas - Massachusetts General Hospital Department of Neurology, Harvard, Charlestown, Massachusetts, USAC Frost - London School of Hygiene and Tropical Medicine, London, UKD R Langbehn - Departments of Psychiatry and Biostatistics (Secondary), University of Iowa, Iowa City, Iowa, USAR I Scahill - UCL Institute of Neurology, University College London, London, UKJ C Stout - School of Psychology, Psychiatry, and Psychological Medicine, Monash University, Victoria, Australia
- Resource Type
- Journal article
- Publication Details
- Journal of neurology, neurosurgery and psychiatry, Vol.81(Suppl 1), pp.A33-A33
- DOI
- 10.1136/jnnp.2010.222653.1
- ISSN
- 0022-3050
- eISSN
- 1468-330X
- Language
- English
- Date published
- 09/2010
- Academic Unit
- Psychiatry; Electrical and Computer Engineering; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
- Record Identifier
- 9984066386102771
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