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Imaging
G01 Evaluation of multi-modal, multi-site imaging measures in Huntington's disease: baseline results from the PADDINGTON study
  1. NZ Hobbs1,
  2. J Cole1,
  3. RE Farmer2,
  4. EM Rees1,
  5. RI Scahill1,
  6. HE Crawford1,
  7. RAC Roos3,
  8. R Sprengelmeyer4,
  9. A Durr5,
  10. B Landwehrmeyer4,
  11. SJ Tabrizi1,
  12. C Frost2
  1. 1UCL Institute of Neurology, University College London, London, UK
  2. 2Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
  3. 3Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
  4. 4Department of Neurology, Ulm University, Ulm, Germany
  5. 5Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France

Abstract

Background Macro- and micro-structural brain changes are of interest as markers of Huntington's Disease (HD) progression, which may prove useful in future clinical trials. The relative sensitivity of these markers is unknown.

Aims To evaluate macro-structural volume measurements and micro-structural diffusion measurements in HD.

Methods 40 controls and 61 early stage HD subjects, recruited across four EU sites, underwent 3T MRI plus a clinical and cognitive battery. Volumetric measurements of the whole brain, caudate, putamen, corpus callosum and ventricles were performed using MIDAS. Diffusion metrics of fractional anisotropy (FA), mean- radial- and axial-diffusivity (MD, RD and AD) were computed over the white matter, corpus callosum, caudate and putamen. Group differences were examined adjusting for age, gender and site.

Results Compared with controls, HD subjects showed strong evidence of reduced volume in all brain regions examined (p<0.001), except for the ventricles which were enlarged (p<0.01). The largest volumetric effect sizes were for the putamen (−2.405, 95% CI −2.942 to −1.753) and caudate (−2.346, 95% CI −2.956 to −1.576). All diffusion metrics showed significant differences between controls and HD (p<0.05), with the exception of white-matter FA (p=0.053). The largest diffusion effect sizes were seen in the caudate and putamen diffusivity metrics; putamen AD showed an effect size of 1.882 (95% CI 1.396 to 2.178). Effect sizes tended to be smaller for diffusion metrics than the corresponding volumetrics. A statistical analysis of these differences will be presented.

Conclusion Both volumetric and diffusion metrics are sensitive to disease effects in HD. Robust statistical comparison of effect sizes for these measures will help inform the design of future clinical trials.

Funding This work has been supported by the European Union – PADDINGTON project, contract n. HEALTH-F2-2010-261358.

  • Neuroimaging
  • multi-modal
  • biomarkers

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