Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data
Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data
复制标题
DOI：
10.1192/bjp.bp.114.156588
复制
发表时间：
2016-06-01
影响因子：
10.5
通讯作者：
Georgiou-Karistianis, Nellie
中科院分区：
文献类型：
--
作者：
Dominguez, Juan F.;Stout, Julie C.;Georgiou-Karistianis, Nellie
背景在亨廷顿舞蹈病等神经退行性疾病中发现潜在的疾病缓解疗法取决于敏感生物标志物的可用性，这些生物标志物反映了疾病各个阶段的衰退，并且在功能和临床上相关。目的量化患有预兆和有症状亨廷顿舞蹈病的参与者在 30 个月内的宏观结构和微观结构变化，并确定其功能和临床相关性。方法多模态磁性 共振成像研究测量了 40 名患有预兆亨廷顿病的患者、36 名有症状的亨廷顿病患者和 36 名健康对照参与者在 30 个月的 3 次测试中的宏观结构（体积）和微观结构（扩散性）测量的变化。结果与对照相比，有症状的亨廷顿病参与者的全脑、灰质、尾状核和尾状核有更大的纵向萎缩。 壳核，以及尾状核各向异性分数增加；尾状核体积减少是亨廷顿病发作前和对照组之间唯一不同的指标。尾状核体积和分数各向异性的变化与神经认知能力下降相互相关；尾状核体积减少也与临床和疾病严重程度相关。结论尾状神经变性，尤其是萎缩，可能是在即将进行的临床试验的开发中考虑的最合适的候选替代生物标志物。
BackgroundThe 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.AimsTo 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.MethodMultimodal 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.ResultsRelative 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.ConclusionsCaudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.