A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease.
A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease.
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DOI：
10.3389/fdata.2021.662200
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发表时间：
2021
影响因子：
3.1
通讯作者：
Alexander DC
中科院分区：
文献类型：
--
作者：
Wijeratne PA;Johnson EB;Gregory S;Georgiou-Karistianis N;Paulsen JS;Scahill RI;Tabrizi SJ;Alexander DC
了解神经变性生物标志物的变化顺序和进展对于检测药物干预对这些生物标志物的影响至关重要。在亨廷顿病（HD）中，运动、认知和MRI生物标志物目前用于药物疗效的临床试验。在这里，我们首次使用基于事件的概率模型（EBM）直接比较了三项大型HD观察性研究（总N = 532）的数据，以确定运动、认知和MRI生物标志物异常的顺序。我们还调查了遗传因素的影响，HD，胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复长度，通过这些阶段的进展。我们发现，循证医学揭示了一个广泛一致的顺序的事件在所有三项研究中，循证医学阶段反映临床阶段，循证医学阶段与年龄和遗传负担。我们的研究结果表明，皮质下和白色物质体积的措施变得异常之前，临床和认知生物标志物。重要的是，CAG重复长度对每个阶段的发作时间和阶段进展有很大影响，较长的重复长度导致更早的发作和更快的进展。我们的研究结果可用于帮助设计亨廷顿病治疗的临床试验，影响生物标志物的选择和参与者的招募。
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.
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影响因子：
3.5
作者：
Langbehn, DR;Brinkman, RR;Hayden, MR
通讯作者：
Hayden, MR
DOI：
10.1016/j.nicl.2017.10.023
发表时间：
2018
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Minkova L;Gregory S;Scahill RI;Abdulkadir A;Kaller CP;Peter J;Long JD;Stout JC;Reilmann R;Roos RA;Durr A;Leavitt BR;Tabrizi SJ;Klöppel S;TRACK-HD Investigators
通讯作者：
TRACK-HD Investigators
影响因子：
4.8
作者：
Oxtoby NP;Alexander DC;EuroPOND consortium
通讯作者：
EuroPOND consortium
影响因子：
5.7
作者：
Fonteijn, Hubert M.;Modat, Marc;Alexander, Daniel C.
通讯作者：
Alexander, Daniel C.
影响因子：
10.6
作者：
Cardoso, M. Jorge;Modat, Marc;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien