A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington’s Disease
| العنوان: | A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington’s Disease |
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| المؤلفون: | Peter A. Wijeratne, Eileanoir B. Johnson, Sarah Gregory, Nellie Georgiou-Karistianis, Jane S. Paulsen, Rachael I. Scahill, Sarah J. Tabrizi, Daniel C. Alexander |
| المصدر: | Frontiers in Big Data, Vol 4 (2021) Frontiers in Big Data |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Big Data, 0301 basic medicine, Oncology, medicine.medical_specialty, multi-study investigation, Information technology, Disease, Efficacy, 03 medical and health sciences, 0302 clinical medicine, Huntington's disease, huntington’s disease, Artificial Intelligence, Internal medicine, clinical staging, Computer Science (miscellaneous), Medicine, Stage (cooking), disease progression model, Original Research, business.industry, Neurodegeneration, biomarkers, Cognition, T58.5-58.64, medicine.disease, Clinical trial, 030104 developmental biology, Observational study, business, 030217 neurology & neurosurgery, Information Systems |
| الوصف: | 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. |
| تدمد: | 2624-909X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30ded65ab251e2528f9eaae52829e46dTest https://doi.org/10.3389/fdata.2021.662200Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....30ded65ab251e2528f9eaae52829e46d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2624909X |
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