Progression marker of Parkinson's disease: a 4-year multi-site imaging study.
Progression marker of Parkinson's disease: a 4-year multi-site imaging study.
复制标题
DOI：
10.1093/brain/awx146
复制
发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Vaillancourt DE
中科院分区：
文献类型：
--
作者：
Burciu RG;Ofori E;Archer DB;Wu SS;Pasternak O;McFarland NR;Okun MS;Vaillancourt DE
帕金森病的进展标志物对治疗发展至关重要。Burciu等人在一项国际新生帕金森病队列的1年和4年随访中验证了黑质中游离水作为进展标志物的有效性。一年的自由水变化可以预测四年运动症状的进展。帕金森病的进展标志物对成功的治疗发展至关重要。最近，一种使用咬传感器模型的扩散磁共振成像分析技术被引入，可以估计一个体素内自由水的分数体积，这有望增加神经退行性疾病，如帕金森病。先前的研究表明，帕金森病患者的后黑质游离水在单位点和多位点队列中比对照组升高，帕金森病患者的游离水在1年内增加，但在单位点的对照组中没有增加。本研究的目的是验证后黑质游离水作为帕金森病进展标志物的有效性，并在一项多中心国际帕金森病纵向研究中对患者进行了4年随访，描述游离水的进展模式（http://www.ppmi-info.org/）。分析检查了：(i) 103名帕金森病新发患者和49名对照者1年内游离水的变化；（ii） 46例帕金森病患者在基线、12、24和48个月成像的2年和4年游离水变化；（iii）自由水1年和2年的变化是否能预测Hoehn和Yahr尺度4年的变化；（iv）同时接受扩散和多巴胺转运体成像的帕金森病亚组4年游离水和纹状体结合率变化之间的关系。结果表明：(i)帕金森病患者后黑质游离水水平在1年内增加，而对照组没有；（ii）帕金森病患者体内游离水分在4年内持续增加；（iii）性别和基线自由水预测4年自由水的变化；(4) 1年和2年的自由水量增加与4年的Hoehn和Yahr尺度恶化有关；(5)壳核纹状体结合率4年下降与游离水分4年增加有关。重要的是，所有的纵向结果都是一致的。总之，这项研究表明，在一项多地点队列研究中，一大批帕金森病新发患者的后黑质游离水在1年内增加，而在健康对照组中没有变化，并进一步证明帕金森病患者的游离水在4年内增加。一个关键的发现是各部位的结果是一致的，1年和2年后黑质游离水的增加预示着Hoehn和Yahr分期系统的长期进展。总之，这些发现表明，后黑质中的游离水是帕金森病的有效进展成像标志物，可用于疾病改善疗法的临床试验。
Progression markers of Parkinson’s disease are crucial for therapeutic development. Burciu et al. validate free-water in the substantia nigra as a progression marker at one- and four-year follow-up, in an international cohort of de novo Parkinson’s disease. One-year changes in free-water predict the progression of motor symptoms over four years. Progression markers of Parkinson’s disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson’s disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson’s disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson’s disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson’s disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson’s disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson’s disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson’s disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson’s disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson’s disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson’s disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson’s disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson’s disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson’s disease, which may be used in clinical trials of disease-modifying therapies.
登录
查看更多内容
影响因子：
2.8
作者：
Henchcliffe, Claire;Severt, W. Lawrence
通讯作者：
Severt, W. Lawrence
影响因子：
4.2
作者：
Ofori E;Pasternak O;Planetta PJ;Burciu R;Snyder A;Febo M;Golde TE;Okun MS;Vaillancourt DE
通讯作者：
Vaillancourt DE
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
11.2
作者：
Olanow, C. Warren;Kleburtz, Karl;Schapira, Anthony H. V.
通讯作者：
Schapira, Anthony H. V.
影响因子：
4.8
作者：
Albi A;Pasternak O;Minati L;Marizzoni M;Bartrés-Faz D;Bargalló N;Bosch B;Rossini PM;Marra C;Müller B;Fiedler U;Wiltfang J;Roccatagliata L;Picco A;Nobili FM;Blin O;Sein J;Ranjeva JP;Didic M;Bombois S;Lopes R;Bordet R;Gros-Dagnac H;Payoux P;Zoccatelli G;Alessandrini F;Beltramello A;Ferretti A;Caulo M;Aiello M;Cavaliere C;Soricelli A;Parnetti L;Tarducci R;Floridi P;Tsolaki M;Constantinidis M;Drevelegas A;Frisoni G;Jovicich J;PharmaCog Consortium
通讯作者：
PharmaCog Consortium