Unsupervised subtyping of motor dysfunction of Parkinson's disease and its structural brain imaging correlates

Q4 Neuroscience

Neuroimage. Reports Pub Date : 2025-03-01 DOI:10.1016/j.ynirp.2025.100246

Yu-Fan Lin , Jong-Ling Fuh , Albert C. Yang

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Abstract

Background

Parkinson's disease (PD) is a clinical neurodegenerative disorder. The Unified Parkinson's Disease Rating Scale (UPDRS) has been used as a standard measure of the PD symptom profile, and magnetic resonance (MR) imaging is widely used for identifying the critical brain regions involved in PD progression.

Objectives

The present study aimed to (1) identify PD subtypes based on the motor dysfunction profile in the MDS-UPDRS and (2) find the differences in gray matter volumes of brain regions, and (3) compare non-motor features between the subtypes to explore their distinct clinical profiles.

Methods

In total, 299 patients with PD and 173 healthy participants from the Parkinson's Progression Markers Initiative were included. A software package, Generalized Association Plots, was used to cluster the motor dysfunction profile in the MDS-UPDRS. Regression models and the Artificial Intelligence Platform as a Service were used to quantify the differences in gray matter volume of brain regions between subtypes.

Results

We identified three PD subtypes—resting tremor, intermediate, and akinetic-rigid—using motor symptom clustering. MRI analysis revealed significant differences in brain regions, including the posterior cingulate gyrus, lenticular nucleus, olfactory cortex, and cerebellum. Non-motor features, such as cognitive decline and autonomic dysfunctions, varied across subtypes, highlighting distinct systemic profiles. Akinetic-rigid patients exhibited the most severe impairments, while tremor-dominant patients showed milder non-motor symptoms.

Discussion

Three PD subtypes of motor dysfunction were identified. Structural brain imaging revealed subtype-specific differences not only in cingulum and putamen regions, but also in the olfactory cortex, parahippocampal gyrus, and cerebellum, correlating with motor symptoms. Non-motor features varied by subtype, with increasing severity from tremor-dominant to akinetic-rigid.

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帕金森病运动功能障碍的无监督分型及其脑结构成像相关性

帕金森病（PD）是一种临床神经退行性疾病。统一帕金森病评定量表（UPDRS）已被用作PD症状概况的标准测量，磁共振（MR）成像被广泛用于识别PD进展中涉及的关键脑区。目的本研究旨在(1)根据MDS-UPDRS的运动功能障碍特征确定PD亚型；(2)发现脑区灰质体积的差异；(3)比较亚型之间的非运动特征以探索其不同的临床特征。方法共纳入299名PD患者和173名来自帕金森进展标志物计划的健康参与者。一个软件包，广义关联图，用于在MDS-UPDRS中对运动功能障碍概况进行聚类。使用回归模型和人工智能平台即服务来量化不同亚型大脑区域灰质体积的差异。结果通过运动症状聚类，我们确定了三种PD亚型——静息性震颤、中度震颤和动性刚性震颤。MRI分析显示，大脑区域有显著差异，包括扣带回后区、透镜状核、嗅觉皮层和小脑。非运动特征，如认知能力下降和自主神经功能障碍，在不同亚型中有所不同，突出了不同的系统特征。动刚型患者表现出最严重的损伤，而震颤型患者表现出较轻的非运动症状。PD的运动功能障碍分为三种亚型。脑结构成像显示，不仅在扣带和壳核区域，而且在嗅觉皮层、海马旁回和小脑也存在亚型特异性差异，这些差异与运动症状相关。非运动特征因亚型而异，从震颤为主到运动僵硬的严重程度逐渐增加。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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