In:
Frontiers in Big Data, Frontiers Media SA, Vol. 4 ( 2021-8-5)
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 of Medium:
Online Resource
ISSN:
2624-909X
DOI:
10.3389/fdata.2021.662200
DOI:
10.3389/fdata.2021.662200.s001
DOI:
10.3389/fdata.2021.662200.s002
DOI:
10.3389/fdata.2021.662200.s003
DOI:
10.3389/fdata.2021.662200.s004
DOI:
10.3389/fdata.2021.662200.s005
DOI:
10.3389/fdata.2021.662200.s006
DOI:
10.3389/fdata.2021.662200.s007
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2957497-3
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