One-year changes in brain microstructure differentiate preclinical Huntington's disease stages
Objective: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. Methods: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotro...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158219304462 |
| _version_ | 1818034301223043072 |
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| author | Chris Patrick Pflanz Marina Charquero-Ballester D.S. Adnan Majid Anderson M. Winkler Emmanuel Vallée Adam R. Aron Mark Jenkinson Gwenaëlle Douaud |
| author_facet | Chris Patrick Pflanz Marina Charquero-Ballester D.S. Adnan Majid Anderson M. Winkler Emmanuel Vallée Adam R. Aron Mark Jenkinson Gwenaëlle Douaud |
| author_sort | Chris Patrick Pflanz |
| collection | DOAJ |
| description | Objective: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. Methods: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. Results: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. Conclusions: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease. Keywords: Preclinical Huntington's disease, Longitudinal, Microstructure, Corpus callosum, Basal ganglia, Diffusion imaging |
| first_indexed | 2024-12-10T06:36:59Z |
| format | Article |
| id | doaj.art-e0bd75be8f75461f84db2d082482b68d |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-10T06:36:59Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-e0bd75be8f75461f84db2d082482b68d2022-12-22T01:58:55ZengElsevierNeuroImage: Clinical2213-15822020-01-0125One-year changes in brain microstructure differentiate preclinical Huntington's disease stagesChris Patrick Pflanz0Marina Charquero-Ballester1D.S. Adnan Majid2Anderson M. Winkler3Emmanuel Vallée4Adam R. Aron5Mark Jenkinson6Gwenaëlle Douaud7Oxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UKOxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Department of Psychiatry, University of Oxford, UKDepartment of Psychology, University of California, San Diego (UCSD), San Diego, California, USAOxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UKOxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UKDepartment of Psychology, University of California, San Diego (UCSD), San Diego, California, USAOxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UKOxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Corresponding author: Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.Objective: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. Methods: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. Results: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. Conclusions: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease. Keywords: Preclinical Huntington's disease, Longitudinal, Microstructure, Corpus callosum, Basal ganglia, Diffusion imaginghttp://www.sciencedirect.com/science/article/pii/S2213158219304462 |
| spellingShingle | Chris Patrick Pflanz Marina Charquero-Ballester D.S. Adnan Majid Anderson M. Winkler Emmanuel Vallée Adam R. Aron Mark Jenkinson Gwenaëlle Douaud One-year changes in brain microstructure differentiate preclinical Huntington's disease stages NeuroImage: Clinical |
| title | One-year changes in brain microstructure differentiate preclinical Huntington's disease stages |
| title_full | One-year changes in brain microstructure differentiate preclinical Huntington's disease stages |
| title_fullStr | One-year changes in brain microstructure differentiate preclinical Huntington's disease stages |
| title_full_unstemmed | One-year changes in brain microstructure differentiate preclinical Huntington's disease stages |
| title_short | One-year changes in brain microstructure differentiate preclinical Huntington's disease stages |
| title_sort | one year changes in brain microstructure differentiate preclinical huntington s disease stages |
| url | http://www.sciencedirect.com/science/article/pii/S2213158219304462 |
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