Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson’s disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4–5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.

皮层下大脑区域的改变与帕金森病 （PD） 的运动和非运动症状有关。然而，临床表达与基底神经节、丘脑、杏仁核和海马的区域形态学异常之间的关联尚未得到很好的确立。我们分析了来自 ENIGMA-PD 联盟中 2525 个全球来源的 1326 名 PD 患者的 3D T1 加权脑部 MRI 和临床数据。我们使用质量单变量和多变量模型研究了疾病对 7 个双侧皮层下结构的 27,120 个顶点的内侧厚度的影响。在所有 Hoehn 和 Yahr （HY） 阶段观察到形状差异，以及与运动和认知症状的相关性。值得注意的是，我们观察到 HY1 的壳核、HY2 的尾状核和杏仁核、HY3 的海马、伏隔核和丘脑以及 HY4-5 的苍白球逐渐变薄。丘脑的亚区在 HY1 和 HY2 中较厚。基本一致的模式与诊断后较长的时间以及较差的运动症状和认知表现相关。多变量回归揭示了预测疾病分期的模式。这些横断面发现通过展示疾病阶段特异性形态的模式，为 PD 皮质下变性提供了新的见解，这与正在进行的变性基本一致。