Henley, S.; (2008) MRI and cognitive changes in Huntington's disease. Doctoral thesis , University of London.

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Abstract

This thesis focused on cognitive and MRI measures of early change and progression in Huntington's disease (HD). HD is clinically heterogeneous and previous findings about the location of brain atrophy in the early stages, and its relation to cognition, are equivocal. A pilot study assessed the practicality of using serial volumetric MRI in early HD and the usefulness of cognitive tasks in longitudinal assessment. A larger study investigated cross-sectional and longitudinal aspects of these domains in premanifest and early HD. Global and regional cerebral volumes were investigated using manual volumetry and voxel-based morphometry (VBM). The work describes the application of the Brain Boundary Shift Integral (BBSI) to measure of whole-brain atrophy rate. Preparatory technical work included choice of templates for optimum scan alignment and segmentation in VBM, and adjustment of BBSI parameters to obtain maximum agreement between it and manual measures. Cognitive ability was assessed using a wide-ranging battery of tests, some standard and some novel. Atrophy in early HD was found to be more extensive than previously reported, involving widespread extra-striatal loss, and not all functional deficits could be attributed to striatal damage. Emotion recognition deficits were broad and associated with striatal and extra-striatal brain regions. Executive function and memory tasks demonstrated decline over one year. Whole-brain atrophy rates were increased in early HD and associated with decline in cognition and CAG repeat length. This work elucidates the extent of, and associations of, atrophy and cognitive impairment in HD, and adds weight to the suggestion that variability in progression rates is partly explained by genetic factors. The suggestion that motor learning might be impaired even in very far-from-onset gene carriers, and that tasks other than those tapping executive function were sensitive to decline, should motivate further work aimed at detecting the very earliest signs of change in this disease.

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