多模态影像生物标志物在未显症和早期亨廷顿病中的应用：IMAGE-HD 研究 30 个月数据。
Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data.
机构信息
Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia
出版信息
Br J Psychiatry. 2016 Jun;208(6):571-8. doi: 10.1192/bjp.bp.114.156588. Epub 2015 Dec 17.
BACKGROUND
The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant.
AIMS
To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance.
METHOD
Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months.
RESULTS
Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity.
CONCLUSIONS
Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.
背景
在亨廷顿病等神经退行性疾病中发现潜在的疾病修饰疗法，取决于是否有敏感的生物标志物，这些标志物可以反映疾病各阶段的下降情况，并且具有功能和临床相关性。
目的
在 30 个月的时间内，定量测量无症状和有症状亨廷顿病患者的宏观和微观结构变化，并确定其功能和临床相关性。
方法
对 40 名无症状亨廷顿病患者、36 名有症状亨廷顿病患者和 36 名健康对照参与者进行多模态磁共振成像研究，测量 30 个月内 3 次测试期间的宏观结构（体积）和微观结构（扩散性）变化。
结果
与对照组相比，有症状亨廷顿病患者的整个大脑、灰质、尾状核和壳核的纵向萎缩程度更大，尾状核的各向异性分数也增加；尾状核体积的丧失是无症状亨廷顿病和对照组之间唯一的差异。尾状核体积和各向异性分数的变化相互关联，与神经认知下降相关；尾状核体积的丧失也与临床和疾病严重程度相关。
结论
尾状核神经退行性变，特别是萎缩，可能是最适合在即将进行的临床试验中考虑的候选替代生物标志物。
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