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The Progression of Regional Atrophy in Premanifest and Early Huntington’s Disease: A Longitudinal Voxel-Based Morphometry Study
  1. Nicola Z Hobbs1,*,
  2. Susie M D Henley1,
  3. Gerard Ridgway1,
  4. Edward J Wild1,
  5. Roger Barker2,
  6. Rachael I Scahill1,
  7. Josephine Barnes1,
  8. Nick C Fox1,
  9. Sarah Tabrizi1
  1. 1 UCL Institute of Neurology, United Kingdom;
  2. 2 Department of clinical neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom
  1. Correspondence to: Nicola Zoe Hobbs, UCL Institute of Neurology, Box 16 NHNN, Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, United Kingdom; hobbs{at}drc.ion.ucl.ac.uk

Abstract

Background: Unbiased longitudinal studies are needed to understand the distributed neurodegenerative changes of Huntington’s disease (HD). They may also provide tools for assessing disease-modifying interventions. We investigated the progression of regional atrophy in premanifest and early HD compared with controls.

Methods: Nine controls, 17 premanifest and 21 early HD subjects underwent volumetric MRI at baseline and two years. Premanifest subjects were on average 18.1 years before predicted motor onset. Non-linear registration was used to model within-subject change over the scanning interval and statistical parametric mapping was used to examine group differences and associations with clinical variables.

Results: In early HD, increased grey-matter (GM) atrophy rates were evident throughout the sub-cortical GM and over selective cortical regions compared with controls. This group also demonstrated strikingly widespread increases in white-matter (WM) atrophy rates. We observed no significant differences between premanifest and controls. Longer CAG was associated with higher atrophy rates over large WM areas including brainstem and internal capsule and over small GM regions including thalamus and occipital cortex. Worse baseline motor score was associated with regionally increased rates in the thalamus, internal capsule and occipital lobe. Sample-size calculations indicate 19 and 24 early HD subjects per treatment arm would need to complete a two-year trial in order to detect a 50% reduction in WM and GM atrophy rates respectively.

Conclusions: Degeneration of structural connectivity may play an important role in early HD symptoms. Assessment of WM and GM changes will be important in understanding the complexity of HD and its treatment.

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