Fereshtehnejad Seyed-Mohammad, Moqadam Roqaie, Azizi Houman, Postuma Ronald B, Dadar Mahsa, Lang Anthony E, Marras Connie, Zeighami Yashar
Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
Mov Disord. 2025 Aug;40(8):1572-1583. doi: 10.1002/mds.30229. Epub 2025 May 26.
Parkinson's disease (PD) varies widely across individuals in clinical manifestations and course of progression. Identification of distinct biological subtypes could explain this heterogeneity, identify its pathophysiology, and predict disease progression.
Our aim was to compare longitudinal clinical trajectories and brain atrophy patterns between clinical subtypes defined at the baseline de novo PD.
We analyzed data from 421 PD patients (mean follow-up: 8.2 years) in the Parkinson's Progression Markers Initiative (PPMI). Using multi-domain motor and non-motor criteria, de novo patients were classified into "mild motor-predominant" (n = 223), "intermediate" (n = 146), and "diffuse-malignant" (n = 52) subtypes. Deformation-based morphometry was performed on T1-weighted magnetic resonance imaging (MRIs) from 128 PD patients with at least two MRIs (71 mild motor-predominant, 42 intermediate, and 15 diffuse-malignant) and 60 controls, with an average MRI follow-up duration of 3.4 ± 1.1 in the PD cohort. Mixed-effects models compared clinical progression and longitudinal pattern of regional atrophy across subtypes.
The diffuse-malignant subtype exhibited faster worsening of motor severity (P = 0.007), cognition (P < 0.0001), and activities of daily living (P < 0.0001) compared to mild motor-predominant subtype over 8 years. These findings remained statistically significant after an age-matched subgroup analysis and adjustment for the levodopa treatment. Accelerated atrophy was observed in the precuneus, temporal and fusiform gyri, cerebellum, and other regions (corrected-P < 0.05).
Longitudinal analysis revealed distinct patterns of clinical progression and regional atrophy in PD subtypes, with the diffuse-malignant subtype showing more severe neurodegeneration and clinical deterioration suggesting existence of diverse pathophysiological mechanisms in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
帕金森病（PD）在个体的临床表现和疾病进展过程中差异很大。识别不同的生物学亚型可以解释这种异质性，确定其病理生理学，并预测疾病进展。
我们的目的是比较在基线新发帕金森病时定义的临床亚型之间的纵向临床轨迹和脑萎缩模式。
我们分析了帕金森病进展标志物计划（PPMI）中421例帕金森病患者的数据（平均随访时间：8.2年）。使用多领域运动和非运动标准，将新发患者分为“轻度运动为主型”（n = 223）、“中间型”（n = 146）和“弥漫恶性型”（n = 52）亚型。对128例至少有两次磁共振成像（MRI）的帕金森病患者（71例轻度运动为主型、42例中间型和15例弥漫恶性型）和60例对照者的T1加权MRI进行基于变形的形态测量，帕金森病队列中MRI的平均随访时间为3.4±1.1年。混合效应模型比较了各亚型的临床进展和区域萎缩的纵向模式。
与轻度运动为主型亚型相比，弥漫恶性型亚型在8年期间运动严重程度（P = 0.007）、认知（P < 0.0001）和日常生活活动能力（P < 0.0001）的恶化更快。在年龄匹配的亚组分析和左旋多巴治疗调整后，这些发现仍具有统计学意义。在楔前叶、颞叶和梭状回、小脑及其他区域观察到加速萎缩（校正P < 0.05）。
纵向分析揭示了帕金森病亚型中不同的临床进展和区域萎缩模式，弥漫恶性型亚型表现出更严重的神经退行性变和临床恶化，提示帕金森病存在多种病理生理机制。© 2025作者。由Wiley Periodicals LLC代表国际帕金森病和运动障碍协会出版的《运动障碍》。
