Abstract Details

Title Data-driven Subtyping of Parkinson’s Disease Using Isotropic Diffusion

Topic Movement Disorders

Presentation(s) P9 - Poster Session 9 (5:00 PM-6:00 PM)

Poster/Presentation
Number 17-009

Objective To evaluate whether isotropic diffusion (ISO), a diffusion MRI-derived metric from generalized q-sampling imaging (GQI), can stratify biologically distinct subtypes of Parkinson’s disease (PD) using a data-driven clustering approach, and to assess whether these subtypes differ in motor progression.

Background PD is clinically heterogeneous, and biologically grounded subtyping may improve prognostic accuracy and guide therapeutic strategies. ISO quantifies extracellular water, with elevated levels linked to neurodegeneration. Whether ISO-based subtyping can delineate biologically distinct PD subgroups with distinct clinical trajectories remains unknown.

Design/Methods We applied an unsupervised, data-driven hierarchical clustering approach to baseline ISO values from 12 subcortical regions central to PD pathology in 156 de novo patients from the Parkinson’s Progression Markers Initiative. Subtypes were compared on baseline motor severity (MDS-UPDRS-III total and subdomains: bradykinesia, rigidity, tremor, postural instability/gait difficulty) and on longitudinal changes in ISO and motor outcomes over 4 years using mixed-effects models.

Results Two subtypes emerged: Subtype 1 (n=62) with lower baseline ISO and Subtype 2 (n=94) with higher ISO across all regions. At baseline, Subtype 2 showed greater rigidity (p=0.004) and bradykinesia (p=0.01), with no differences in tremor or postural instability/gait difficulty. Longitudinally, Subtype 1 exhibited progressive ISO increases across regions (p<0.001), while Subtype 2 remained stable at elevated levels. Despite these divergent imaging trajectories, both subtypes progressed at similar rates, with no differences in longitudinal motor trajectories.

Conclusions Clustering of ISO values from GQI identified distinct PD subgroups with divergent imaging trajectories, but these did not correspond to differences in motor progression. ISO may capture extracellular heterogeneity in PD, although its prognostic value remains uncertain. Larger cohorts and longer follow-up are needed to clarify its clinical utility for stratification in care and trials.

Authors/Disclosures
Anupa Ambili Vijayakumari, PhD (Cleveland Clinic) PRESENTER	Dr. Ambili Vijayakumari has nothing to disclose.
Daniel Teixeira dos Santos, Sr., MD	Dr. Teixeira dos Santos has nothing to disclose.
Ken Sakaie, PhD	The institution of Dr. Sakaie has received research support from NIH. The institution of Dr. Sakaie has received research support from National Multiple Sclerosis Society. The institution of Dr. Sakaie has received research support from DOD. The institution of Dr. Sakaie has received research support from Chiari and Syringomyelia Foundation. The institution of Dr. Sakaie has received research support from American Heart Association. The institution of Dr. Sakaie has received research support from PCORI. The institution of Dr. Sakaie has received research support from Genzyme. The institution of Dr. Sakaie has received research support from Novartis. The institution of Dr. Sakaie has received research support from Keep Memory Alive Foundation.
Hubert H. Fernandez, MD, FAAN (Center for Neurological Restoration, Cleveland Clinic)	Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intrance. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Fernandez has received publishing royalties from a publication relating to health care. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as a Steering Committee/Advisory Committee Member with Parkinson Study Group.
Benjamin L. Walter, MD (Cleveland Clinic)	Dr. Walter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda. Dr. Walter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lundbeck. Dr. Walter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medtronic. Dr. Walter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Walter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbott.

��ɫ��

��ɫ��