Progressive alterations in white matter microstructure across the timecourse of Huntington's disease

Brain and Behavior, vol. 13, pp. e2940

Abstract

BACKGROUND: Whole-brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD). METHODS: We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden. The TrackOn-HD study included 67 controls, 67 premanifest, and 10 early manifest HD (baseline and 24-month data); the PADDINGTON study included 33 controls and 49 early manifest HD (baseline and 15-month data). Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity from baseline to last study visit were investigated for each cohort using tract-based spatial statistics. An optimized pipeline was employed to generate participant-specific templates to which diffusion tensor imaging maps were registered and change maps were calculated. We examined longitudinal differences between HD expansion-carriers and controls, and correlations with clinical scores, including the composite UHDRS (cUHDRS). RESULTS: HD expansion-carriers from TrackOn-HD, with lower disease burden, showed a significant longitudinal decline in FA in the left superior longitudinal fasciculus and an increase in MD across subcortical WM tracts compared to controls, while in manifest HD participants from PADDINGTON, there were significant widespread longitudinal increases in diffusivity compared to controls. Baseline scores in clinical scales including the cUHDRS predicted WM microstructural change in HD expansion-carriers. CONCLUSION: The present study showed significant longitudinal changes in WM microstructure across the HD timecourse. Changes were evident in larger WM areas and across more metrics as the disease advanced, suggesting a progressive alteration of WM microstructure with disease evolution.

Authors 14

1. Carlos Estevez‐Fraga

   UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

   Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

2. Michael S. Elmalem

   UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

   Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

3. Marina Papoutsi

   UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

   Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

4. Alexandra Dürr

   Centre National de la Recherche Scientifique · Inserm · Sorbonne Université · Institut du Cerveau

   Affiliation as printed

   Sorbonne Université, Paris Brain Institute (ICM), AP‐HP, Inserm, CNRS Pitié‐Salpêtrière University Hospital Paris France

5. Elin M. Rees

   Ixico (United Kingdom)

   Affiliation as printed

   Ixico London UK

   Ixico, London, UK

6. Nicola Z. Hobbs

   UCL Queen Square Institute of Neurology · University College London

   Affiliation as printed

   Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

   Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

7. Raymund A.C. Roos Aachen Department of Neurology Leiden University Medical Centre Leiden The Netherlands Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Neurology Leiden University Medical Centre Leiden The Netherlands

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

8. G. Bernhard Landwehrmeyer

   Universität Ulm

   Affiliation as printed

   Department of Neurology University of Ulm Ulm Germany

   Department of Neurology, University of Ulm, Ulm, Germany

9. Blair R. Leavitt

   University of British Columbia Hospital · University of British Columbia

   Affiliation as printed

   Centre for Huntington's Disease at UBC Hospital, Department of Medical Genetics and Division of Neurology, Department of Medicine University of British Columbia Vancouver BC Canada

   Centre for Huntington's Disease at UBC Hospital, Department of Medical Genetics and Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada

10. Douglas R. Langbehn

    University of Iowa · University of Iowa Health Care

    Affiliation as printed

    Department of Psychiatry University of Iowa Iowa City Iowa USA

    Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA

11. Rachael I. Scahill

    UCL Queen Square Institute of Neurology · University College London

    Affiliation as printed

    Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

    Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

12. Geraint E. Rees

    Wellcome Centre for Human Neuroimaging · UCL Queen Square Institute of Neurology · University College London

    Affiliation as printed

    Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology University College London London UK

    Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, UK

13. Sarah J. Tabrizi

    UCL Queen Square Institute of Neurology · University College London

    Affiliation as printed

    Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

    Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK

14. Sarah Gregory corresponding

    UCL Queen Square Institute of Neurology · University College London

    Affiliation as printed

    Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London London UK

    Huntington's Disease Centre, UCL Queen Square Institute of Neurology, University College London, London, UK