Progressive alterations in white matter microstructure across the timecourse of Huntington's disease
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 ex...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.2940 |
| _version_ | 1797821196532711424 |
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| author | Carlos Estevez‐Fraga Michael S. Elmalem Marina Papoutsi Alexandra Durr Elin M. Rees Nicola Z. Hobbs Raymund A. C. Roos Bernhard Landwehrmeyer Blair R. Leavitt Douglas R. Langbehn Rachael I. Scahill Geraint Rees Sarah J. Tabrizi Sarah Gregory |
| author_facet | Carlos Estevez‐Fraga Michael S. Elmalem Marina Papoutsi Alexandra Durr Elin M. Rees Nicola Z. Hobbs Raymund A. C. Roos Bernhard Landwehrmeyer Blair R. Leavitt Douglas R. Langbehn Rachael I. Scahill Geraint Rees Sarah J. Tabrizi Sarah Gregory |
| author_sort | Carlos Estevez‐Fraga |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T09:49:12Z |
| format | Article |
| id | doaj.art-14760f7b295f464cbc8b231b3d170168 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-13T09:49:12Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-14760f7b295f464cbc8b231b3d1701682023-05-24T14:27:20ZengWileyBrain and Behavior2162-32792023-04-01134n/an/a10.1002/brb3.2940Progressive alterations in white matter microstructure across the timecourse of Huntington's diseaseCarlos Estevez‐Fraga0Michael S. Elmalem1Marina Papoutsi2Alexandra Durr3Elin M. Rees4Nicola Z. Hobbs5Raymund A. C. Roos6Bernhard Landwehrmeyer7Blair R. Leavitt8Douglas R. Langbehn9Rachael I. Scahill10Geraint Rees11Sarah J. Tabrizi12Sarah Gregory13Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKSorbonne Université, Paris Brain Institute (ICM), AP‐HP, Inserm, CNRS Pitié‐Salpêtrière University Hospital Paris FranceIxico London UKHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKDepartment of Neurology Leiden University Medical Centre LeidenThe NetherlandsDepartment of Neurology University of Ulm UlmGermanyCentre for Huntington's Disease at UBC Hospital, Department of Medical Genetics and Division of Neurology, Department of Medicine University of British Columbia Vancouver BC CanadaDepartment of Psychiatry University of Iowa Iowa City Iowa USAHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKWellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology University College London London UKHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKHuntington's Disease Centre UCL Queen Square Institute of Neurology, University College London LondonUKAbstract 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.https://doi.org/10.1002/brb3.2940diffusion tensor imagingHuntington's diseaselongitudinalpresymptomaticsymptomatic |
| spellingShingle | Carlos Estevez‐Fraga Michael S. Elmalem Marina Papoutsi Alexandra Durr Elin M. Rees Nicola Z. Hobbs Raymund A. C. Roos Bernhard Landwehrmeyer Blair R. Leavitt Douglas R. Langbehn Rachael I. Scahill Geraint Rees Sarah J. Tabrizi Sarah Gregory Progressive alterations in white matter microstructure across the timecourse of Huntington's disease Brain and Behavior diffusion tensor imaging Huntington's disease longitudinal presymptomatic symptomatic |
| title | Progressive alterations in white matter microstructure across the timecourse of Huntington's disease |
| title_full | Progressive alterations in white matter microstructure across the timecourse of Huntington's disease |
| title_fullStr | Progressive alterations in white matter microstructure across the timecourse of Huntington's disease |
| title_full_unstemmed | Progressive alterations in white matter microstructure across the timecourse of Huntington's disease |
| title_short | Progressive alterations in white matter microstructure across the timecourse of Huntington's disease |
| title_sort | progressive alterations in white matter microstructure across the timecourse of huntington s disease |
| topic | diffusion tensor imaging Huntington's disease longitudinal presymptomatic symptomatic |
| url | https://doi.org/10.1002/brb3.2940 |
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