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Myelin breakdown in human Huntington's disease: Multi-modal evidence from diffusion MRI and quantitative magnetization transfer

de Bourbon Teles, Jose, Bells, Sonja, Jones, Derek, Coulthard, Elisabeth, Rosser, Anne Elizabeth and Metzler-Baddeley, Claudia 2017. Myelin breakdown in human Huntington's disease: Multi-modal evidence from diffusion MRI and quantitative magnetization transfer. Neuroscience 10.1016/j.neuroscience.2017.05.042

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Huntington’s disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibres between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. Whilst patients’ performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients’ performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasise the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Huntington’s disease; myelin; white matter; basal ganglia; cognition; clinical markers
Publisher: Elsevier
Date of First Compliant Deposit: 7 June 2017
Date of Acceptance: 23 May 2017
Last Modified: 28 Jun 2018 20:35

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