Parkinson’s disease (PD) is clinically heterogeneous, which suggests the existence of subtypes; however, there has been no consensus regarding their characteristics. This study included 633 PD individuals across distinct cohorts: unmedicated de novo PD, medicated PD, mild-moderate PD, and a cohort based on diagnostic work-up in clinical practice. Additionally, 233 controls were included. Clustering based on cortical and subcortical gray matter measures was conducted with and without adjusting for global atrophy in the entire PD sample and validated within each cohort. Subtypes were characterized using baseline and longitudinal demographic and clinical data. Unadjusted results identified three clusters showing a gradient of neurodegeneration and symptom severity across the entire sample and the individual cohorts. When adjusting for global atrophy eight clusters were identified in the entire sample, lacking consistency in individual cohorts. This study identified atrophy-based subtypes in PD, emphasizing the significant impact of global atrophy on subtype number, patterns, and interpretation in cross-sectional analyses.

帕金森病（PD）在临床上具有异质性，这表明存在亚型；然而，对于它们的特性尚未达成共识。这项研究包括不同队列中的 633 名帕金森病患者：未用药的新发帕金森病、药物帕金森病、轻中度帕金森病以及基于临床实践诊断检查的队列。此外，还包括 233 个对照。在对整个 PD 样本中的整体萎缩进行调整或不调整的情况下，进行基于皮质和皮质下灰质测量的聚类，并在每个队列中进行验证。使用基线和纵向人口统计和临床数据来表征亚型。未经调整的结果确定了三个集群，显示整个样本和各个队列的神经退行性变和症状严重程度的梯度。当对整体萎缩进行调整时，在整个样本中发现了八个集群，但各个队列之间缺乏一致性。这项研究确定了帕金森病中基于萎缩的亚型，强调了整体萎缩对亚型数量、模式和横断面分析解释的重大影响。