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有关，导致运动和认知能力下降。然而，由于小型研究中使用了异质方法，出现了相互矛盾的结果。在这里，我们对 PD 进行了一项大型扩散 MRI 研究，整合了来自全球 17 个队列的数据，以确定特定阶段的白质差异概况。使用 ENIGMA-DTI 协议对 1654 名诊断为 PD 的参与者（年龄：20-89 岁；33% 女性）和 885 名对照者（年龄：19-84 岁；47% 女性）的弥散加权 MRI 数据进行分析，以评估白质微观结构。对 Hoehn 和 Yahr (HY) 疾病组和对照组的分数各向异性 (FA) 和平均扩散率 (MD) 的骨架图进行比较，以揭示不同阶段白质变化的概况。我们发现 PD 每个阶段的微观结构改变都有增强的、更广泛的模式，最终几乎所有感兴趣区域的 FA 较低，MD 较高：对于 PD HY 阶段穹窿 FA 差异，Cohen 的 d 效应大小达到d = -1.01 4/5。 HY 第 1 阶段的早期 PD 特征包括整个白质骨骼的较高 FA 和较低 MD，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。虽然早期 PD 被 PD 后期的退行性变化所覆盖，但早期 PD 与 PD 中 FA 较高和 MD 较低相关，这与与该疾病相关的早期代偿性变化一致。