基于神经影像学的帕金森病所致时空萎缩的数据驱动亚型

Neuroimaging-based data-driven subtypes of spatiotemporal atrophy due to Parkinson's disease.

作者信息

Shawa Zeena, Shand Cameron, Taylor Beatrice, Berendse Henk W, Vriend Chris, van Balkom Tim D, van den Heuvel Odile A, van der Werf Ysbrand D, Wang Jiun-Jie, Tsai Chih-Chien, Druzgal Jason, Newman Benjamin T, Melzer Tracy R, Pitcher Toni L, Dalrymple-Alford John C, Anderson Tim J, Garraux Gaëtan, Rango Mario, Schwingenschuh Petra, Suette Melanie, Parkes Laura M, Al-Bachari Sarah, Klein Johannes, Hu Michele T M, McMillan Corey T, Piras Fabrizio, Vecchio Daniela, Pellicano Clelia, Zhang Chengcheng, Poston Kathleen L, Ghasemi Elnaz, Cendes Fernando, Yasuda Clarissa L, Tosun Duygu, Mosley Philip, Thompson Paul M, Jahanshad Neda, Owens-Walton Conor, d'Angremont Emile, van Heese Eva M, Laansma Max A, Altmann Andre, Weil Rimona S, Oxtoby Neil P

机构信息

UCL Hawkes Institute and Department of Medical Physics and Biomedical Engineering, University College London, London WC1E 6BT, United Kingdom.

UCL Hawkes Institute and Department of Computer Science, University College London, London WC1E 6BT, United Kingdom.

出版信息

Brain Commun. 2025 Apr 16;7(2):fcaf146. doi: 10.1093/braincomms/fcaf146. eCollection 2025.

Abstract

Parkinson's disease is the second most common neurodegenerative disease. Despite this, there are no robust biomarkers to predict progression, and understanding of disease mechanisms is limited. We used the Subtype and Stage Inference algorithm to characterize Parkinson's disease heterogeneity in terms of spatiotemporal subtypes of macroscopic atrophy detectable on T1-weighted MRI-a successful approach used in other neurodegenerative diseases. We trained the model on covariate-adjusted cortical thicknesses and subcortical volumes from the largest known T1-weighted MRI dataset in Parkinson's disease, Enhancing Neuroimaging through Meta-Analysis consortium Parkinson's Disease dataset ( = 1100 cases). We tested the model by analyzing clinical progression over up to 9 years in openly-available data from people with Parkinson's disease from the Parkinson's Progression Markers Initiative ( = 584 cases). Under cross-validation, our analysis supported three spatiotemporal atrophy subtypes, named for the location of the earliest affected regions as: '' ( = 359, 33%), '' ( = 237, 22%) and '' ( = 187, 17%). A fourth subgroup having sub-threshold/no atrophy was named '' ( = 317, 29%). Statistical differences in clinical scores existed between the no-atrophy subgroup and the atrophy subtypes, but not among the atrophy subtypes. This suggests that the prime T1-weighted MRI delineator of clinical differences in Parkinson's disease is atrophy severity, rather than atrophy location. Future work on unravelling the biological and clinical heterogeneity of Parkinson's disease should leverage more sensitive neuroimaging modalities and multimodal data.

摘要

帕金森病是第二常见的神经退行性疾病。尽管如此,目前尚无可靠的生物标志物来预测疾病进展,对疾病机制的了解也很有限。我们使用亚型和阶段推断算法,根据在T1加权磁共振成像(MRI)上可检测到的宏观萎缩的时空亚型来描述帕金森病的异质性——这是一种在其他神经退行性疾病中成功应用的方法。我们在帕金森病最大的已知T1加权MRI数据集(通过荟萃分析增强神经影像帕金森病数据集,n = 1100例)的协变量调整皮质厚度和皮质下体积上训练该模型。我们通过分析帕金森病进展标志物倡议组织公开数据中帕金森病患者长达9年的临床进展情况来测试该模型(n = 584例)。在交叉验证下,我们的分析支持三种时空萎缩亚型,根据最早受影响区域的位置命名为:“内侧型”(n = 359,33%)、“外侧型”(n = 237,22%)和“弥漫型”(n = 187,17%)。第四个亚组具有亚阈值/无萎缩,命名为“无萎缩型”(n = 317,29%)。无萎缩亚组与萎缩亚型之间存在临床评分的统计学差异,但萎缩亚型之间不存在差异。这表明,帕金森病临床差异的主要T1加权MRI描绘指标是萎缩严重程度,而非萎缩位置。未来关于揭示帕金森病生物学和临床异质性的工作应利用更敏感的神经影像模式和多模态数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27b/12037470/af1253dfc548/fcaf146_ga.jpg

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