Wijeratne, PA;
Johnson, EB;
Gregory, S;
Georgiou-Karistianis, N;
Paulsen, JS;
Scahill, RI;
Tabrizi, SJ;
(2021)
A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease.
Frontiers in Big Data
, 4
, Article 662200. 10.3389/fdata.2021.662200.
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Abstract
Understanding the order and progression of change in biomarkers of neurodegeneration is essential to detect the effects of pharmacological interventions on these biomarkers. In Huntington’s disease (HD), motor, cognitive and MRI biomarkers are currently used in clinical trials of drug efficacy. Here for the first time we use directly compare data from three large observational studies of HD (total N = 532) using a probabilistic event-based model (EBM) to characterise the order in which motor, cognitive and MRI biomarkers become abnormal. We also investigate the impact of the genetic cause of HD, cytosine-adenine-guanine (CAG) repeat length, on progression through these stages. We find that EBM uncovers a broadly consistent order of events across all three studies; that EBM stage reflects clinical stage; and that EBM stage is related to age and genetic burden. Our findings indicate that measures of subcortical and white matter volume become abnormal prior to clinical and cognitive biomarkers. Importantly, CAG repeat length has a large impact on the timing of onset of each stage and progression through the stages, with a longer repeat length resulting in earlier onset and faster progression. Our results can be used to help design clinical trials of treatments for Huntington’s disease, influencing the choice of biomarkers and the recruitment of participants.
| Type: | Article |
|---|---|
| Title: | A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fdata.2021.662200 |
| Publisher version: | https://doi.org/10.3389/fdata.2021.662200 |
| Language: | English |
| Additional information: | Copyright © 2021 Wijeratne, Johnson, Gregory, Georgiou-Karistianis, Paulsen, Scahill, Tabrizi and Alexander. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | huntington’s disease, biomarkers, disease progression model, multi-study investigation, clinical staging |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10133753 |
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