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Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data
Dominguez, Juan Stout, Julie C. Poudel, Govinda Churchyard, Andrew Chua, Phyllis Egan, Gary F. Georgiou-Karistianis, Nellie
Dominguez, Juan
Stout, Julie C.
Poudel, Govinda
Churchyard, Andrew
Chua, Phyllis
Egan, Gary F.
Georgiou-Karistianis, Nellie
Abstract
Background The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant. Aims To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance. Method Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months. Results Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity. Conclusions Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.
Keywords
Date
2016
Type
Journal article
Journal
British Journal of Psychiatry
Book
Volume
208
Issue
6
Page Range
571-578
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
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Open Access Status
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Controlled