Samuel Woodgate1,2, Philippa Morgan-Jones1,3, Susanne Clinch4, Cheney Drew3, Rebecca Playle3, Mohamed Bennasar5, Yulia Hicks1, Catherine Holt1, Anne-Catherine Bachoud-Lévi6,7, Renaud Massart6,7, David Craufurd8,9, Nigel Kirby3, Katy Hamana10, Robin Schubert11, Ralf Reilmann11,12,13, Anne Rosser2,4, Monica Busse14. 1. Cardiff School of Engineering, Cardiff University, Cardiff, United Kingdom. 2. NMRI, School of Medicine, Cardiff University, Cardiff, United Kingdom. 3. Centre for Trials Research, Cardiff University, 4th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, United Kingdom. 4. Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, United Kingdom. 5. School of Computing and Communications, The Open University, Milton Keynes, United Kingdom. 6. Assistance Publique -Hopitaux de Paris, National Centre of Reference for Huntington's Disease, Neurology Department Henri Mondor Hospital, Creteil, France. 7. INSERM U955 01, Institut Mondor de Recherche Biomédicale, UPEC, Créteil-Ecole Normale Supérieure, PSL, Paris, France. 8. Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. 9. Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 10. School of Healthcare Sciences, Cardiff University, Cardiff, United Kingdom. 11. George-Huntington-Institute, Technology-Park, Muenster, Germany. 12. Department of Clinical Radiology, University of Muenster, Muenster, Germany. 13. Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. 14. Centre for Trials Research, Cardiff University, 4th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, United Kingdom. busseme@cardiff.ac.uk.
Abstract
BACKGROUND: The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington's, that is not reliant on clinical expertise for administration. METHODS: One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington's disease completed the Unified Huntington's Disease Rating Scale and the C3t at baseline. Of these, thirty-three were followed up after 12 months. Regression was used to estimate baseline individual and composite clinical scores (including cognitive, motor, and functional ability) using baseline C3t scores. Correlations between C3t and clinical scores were assessed using Spearman's R and visually inspected in relation to disease severity using scatterplots. Effect size over 12 months provided an indication of longitudinal behaviour of the C3t in relation to clinical measures. RESULTS: Baseline C3t scores predicted baseline clinical scores to within 9-13% accuracy, being associated with individual and composite clinical scores. Changes in C3t scores over 12 months were small ([Formula: see text] ≤ 0.15) and mirrored the change in clinical scores. CONCLUSION: The C3t demonstrates promise as a simple, easy to administer, objective outcome measure capable of predicting impairment that is reflective of Huntington's disease severity and offers a viable solution to support remote clinical monitoring. It may also offer utility as a screening tool for recruitment to clinical trials given preliminary indications of association with the prognostic index normed for Huntington's disease.
BACKGROUND: The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington's, that is not reliant on clinical expertise for administration. METHODS: One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington's disease completed the Unified Huntington's Disease Rating Scale and the C3t at baseline. Of these, thirty-three were followed up after 12 months. Regression was used to estimate baseline individual and composite clinical scores (including cognitive, motor, and functional ability) using baseline C3t scores. Correlations between C3t and clinical scores were assessed using Spearman's R and visually inspected in relation to disease severity using scatterplots. Effect size over 12 months provided an indication of longitudinal behaviour of the C3t in relation to clinical measures. RESULTS: Baseline C3t scores predicted baseline clinical scores to within 9-13% accuracy, being associated with individual and composite clinical scores. Changes in C3t scores over 12 months were small ([Formula: see text] ≤ 0.15) and mirrored the change in clinical scores. CONCLUSION: The C3t demonstrates promise as a simple, easy to administer, objective outcome measure capable of predicting impairment that is reflective of Huntington's disease severity and offers a viable solution to support remote clinical monitoring. It may also offer utility as a screening tool for recruitment to clinical trials given preliminary indications of association with the prognostic index normed for Huntington's disease.
Entities:
Keywords:
Convergent validity; Huntington’s disease; Outcome measure; Regression; Upper-limb function
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