NeuroImage: Reports (Mar 2025)
Unsupervised subtyping of motor dysfunction of Parkinson's disease and its structural brain imaging correlates
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.
