Dynamics of Cortical Degeneration Over a Decade in Huntington's Disease.
Dynamics of Cortical Degeneration Over a Decade in Huntington's Disease.
复制标题
DOI：
10.1016/j.biopsych.2020.11.009
复制
发表时间：
2021-04-15
影响因子：
10.6
通讯作者：
Gregory S
中科院分区：
文献类型：
--
作者：
Johnson EB;Ziegler G;Penny W;Rees G;Tabrizi SJ;Scahill RI;Gregory S
表征神经退行性疾病中大脑结构的变化是理解病理长期影响并最终提供治疗靶点的基础。众所周知，亨廷顿舞蹈病（HD）基因携带者在疾病过程中经历进行性脑改变，但皮层萎缩的长期轨迹尚未明确。考虑到目前在HD中测试的基因疗法主要是针对皮层，了解该区域的萎缩是至关重要的。利用来自49名HD基因携带者和49名年龄匹配的对照受试者的至少3次和最多7次脑部扫描的独特纵向数据集，我们实施了一种新的动态系统方法来推断10年来区域神经退行性变的模式。我们使用贝叶斯分层模型来绘制参与者和群体水平的萎缩空间和时间轨迹，另外将萎缩与HD的遗传标记（cag重复长度）以及运动和认知症状联系起来。我们首次表明，神经退行性变化在临床诊断点周围表现出复杂的时间动态和实质性的区域变化。尽管在整个皮层中发现了广泛的组间差异，但枕部和顶叶区域的皮层萎缩率最高。我们已经建立了萎缩和HD遗传标记之间的联系，同时证明了特定的皮质变化可以预测运动和认知能力的下降。HD基因携带者在皮质萎缩的空间模式上表现出区域差异，这与遗传因素、运动和认知症状有关。我们的研究结果表明神经元丢失的复杂模式，这使得HD进展的更大特征。
Characterizing changing brain structure in neurodegeneration is fundamental to understanding long-term effects of pathology and ultimately providing therapeutic targets. It is well established that Huntington’s disease (HD) gene carriers undergo progressive brain changes during the course of disease, yet the long-term trajectory of cortical atrophy is not well defined. Given that genetic therapies currently tested in HD are primarily expected to target the cortex, understanding atrophy across this region is essential. Capitalizing on a unique longitudinal dataset with a minimum of 3 and maximum of 7 brain scans from 49 HD gene carriers and 49 age-matched control subjects, we implemented a novel dynamical systems approach to infer patterns of regional neurodegeneration over 10 years. We use Bayesian hierarchical modeling to map participant- and group-level trajectories of atrophy spatially and temporally, additionally relating atrophy to the genetic marker of HD (CAG-repeat length) and motor and cognitive symptoms. We show, for the first time, that neurodegenerative changes exhibit complex temporal dynamics with substantial regional variation around the point of clinical diagnosis. Although widespread group differences were seen across the cortex, the occipital and parietal regions undergo the greatest rate of cortical atrophy. We have established links between atrophy and genetic markers of HD while demonstrating that specific cortical changes predict decline in motor and cognitive performance. HD gene carriers display regional variability in the spatial pattern of cortical atrophy, which relates to genetic factors and motor and cognitive symptoms. Our findings indicate a complex pattern of neuronal loss, which enables greater characterization of HD progression.
登录
查看更多内容
影响因子：
10.6
作者：
McColgan P;Gregory S;Seunarine KK;Razi A;Papoutsi M;Johnson E;Durr A;Roos RAC;Leavitt BR;Holmans P;Scahill RI;Clark CA;Rees G;Tabrizi SJ;Track-On HD Investigators
通讯作者：
Track-On HD Investigators
影响因子：
5.3
作者：
Halliday, GM;McRitchie, DA;McCusker, E
通讯作者：
McCusker, E
影响因子：
11
作者：
Hobbs, Nicola Z.;Henley, Susie M. D.;Tabrizi, Sarah J.
通讯作者：
Tabrizi, Sarah J.
影响因子：
5.7
作者：
Friston, Karl J.;Mattout, Jeremie;Penny, Will
通讯作者：
Penny, Will
影响因子：
3.4
作者：
Johnson EB;Gregory S;Johnson HJ;Durr A;Leavitt BR;Roos RA;Rees G;Tabrizi SJ;Scahill RI
通讯作者：
Scahill RI