Owens-Walton Conor, Nir Talia M, Al-Bachari Sarah, Ambrogi Sonia, Anderson Tim J, Aventurato Ítalo Karmann, Cendes Fernando, Chen Yao-Liang, Ciullo Valentina, Cook Phil, Dalrymple-Alford John C, Dirkx Michiel F, Druzgal Jason, Emsley Hedley C A, Guimarães Rachel, Haroon Hamied A, Helmich Rick C, Hu Michele T, Johansson Martin E, Kim Ho Bin, Klein Johannes C, Laansma Max, Lawrence Katherine E, Lochner Christine, Mackay Clare, McMillan Corey T, Melzer Tracy R, Nabulsi Leila, Newman Ben, Opriessnig Peter, Parkes Laura M, Pellicano Clelia, Piras Fabrizio, Piras Federica, Pirpamer Lukas, Pitcher Toni L, Poston Kathleen L, Roos Annerine, Silva Lucas Scárdua, Schmidt Reinhold, Schwingenschuh Petra, Shahid-Besanti Marian, Spalletta Gianfranco, Stein Dan J, Thomopoulos Sophia I, Tosun Duygu, Tsai Chih-Chien, van den Heuvel Odile A, van Heese Eva, Vecchio Daniela, Villalón-Reina Julio E, Vriend Chris, Wang Jiun-Jie, Wu Yih-Ru, Yasuda Clarissa Lin, Thompson Paul M, Jahanshad Neda, van der Werf Ysbrand
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Lancaster Medical School, Lancaster University, Lancaster, UK.
NPJ Parkinsons Dis. 2024 Aug 11;10(1):151. doi: 10.1038/s41531-024-00758-3.
The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.
帕金森病（PD）的进展与神经通路的微观结构改变相关，这会导致运动和认知能力下降。然而，由于在小型研究中使用了异质性方法，出现了相互矛盾的结果。在此，我们对帕金森病患者进行了一项大型扩散磁共振成像（MRI）研究，整合了来自全球17个队列的数据，以确定白质差异的阶段特异性特征。使用ENIGMA-DTI协议分析了1654名被诊断为帕金森病的参与者（年龄：20 - 89岁；33%为女性）和885名对照者（年龄：19 - 84岁；47%为女性）的扩散加权MRI数据，以评估白质微观结构。比较了霍恩和亚尔（HY）疾病组及对照组之间的各向异性分数（FA）和平均扩散率（MD）的骨骼化图谱，以揭示不同阶段白质改变的特征。我们发现，随着帕金森病的每个阶段，微观结构改变的模式增强且更广泛，最终在几乎所有感兴趣区域FA降低而MD升高：在帕金森病HY 4/5期，穹窿部FA差异的科恩d效应大小达到d = -1.01。HY 1期早期帕金森病的特征是整个白质骨骼的FA较高而MD较低，其方向与其他神经退行性疾病的典型方向相反。FA和MD与运动和非运动临床功能障碍相关。虽然在帕金森病后期被退行性变化所掩盖，但早期帕金森病与FA反常升高和MD降低相关，这与该疾病相关的早期代偿性变化一致。
