Abstract
<h3>Objective:</h3> To identify neuroanatomical subtypes of patients with Parkinson’s disease (PD) and to define how they differ in motor symptoms. To investigate how the neuroanatomy and motor symptoms of these subtypes change over time. <h3>Background:</h3> Novel approaches to parse the heterogeneity in PD based on neurobiological mechanisms are needed to improve the efforts in precision medicine. Here, we used multimodal imaging data to identify PD subtypes and their progression. <h3>Design/Methods:</h3> T1-weighted, diffusion tensor imaging data and clinical motor scores were obtained from the Parkinson’s Progression Markers Initiative database (www.ppmi-info.org/data) for 61 PD patients at both baseline and 48-month follow-up, and 70 healthy controls (HC) at baseline only. We extracted mean cortical thickness (CTh, reflecting cortical morphometry) from 68 cortical regions, and mean quantitative anisotropy (QA, reflecting the axonal integrity) from 45 white matter tracts. Using Mahalanobis distance, multivariate summary scores of CTh (M<sub>CTh</sub>) and QA (M<sub>QA</sub>) were derived and selected as features for heterogeneity through discriminative analysis. Group differences in neuroanatomical variables (M<sub>CTh,</sub> M<sub>QA</sub>), and motor symptoms between HC and PD subtypes were tested using ANOVA. To assess the longitudinal changes, a linear mixed-effect model was used. <h3>Results:</h3> Three PD subtypes were identified. Subtype 1 showed no detectable neuroanatomical abnormalities and mild motor symptoms at baseline. However, over time, these patients demonstrated substantial axonal degeneration with worsened motor symptoms. Subtype 2 showed cortical atrophy and severe motor symptoms at baseline, but with significant axonal degeneration and absence of changes in motor symptoms over time. Subtype 3 characterized by axonal damage and severe motor symptoms at baseline, displays no neuroanatomical or motor symptom deterioration over time. <h3>Conclusions:</h3> We parsed the heterogeneity of PD using CTh and QA data and identified three distinct PD subtypes with different severity levels of motor symptoms and different patterns of neuroanatomical and symptom progression. <b>Disclosure:</b> Dr. Ambili Vijayakumari has nothing to disclose. 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 Cerevel. 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 $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Fernandez has received research support from Biogen. The institution of Dr. Fernandez has received research support from Michael J Fox Founda. The institution of Dr. Fernandez has received research support from Roche. The institution of Dr. Fernandez has received research support from Parkinson Foundation. The institution of Dr. Fernandez has received research support from UCB. 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. 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.
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