Parkinson Disease Clinical Subtypes: Validation, Clinical Utility, and Biological Correlates

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ABSTRACT Parkinson disease (PD) is a progressive neurodegenerative disease characterized by motor, cognitive, and psychiatric manifestations resulting from abnormal protein deposition and neurotransmitter deficits. The variability in clinical presentation and progression likely reflects different PD subtypes, which may be associated with the underlying variability in brain pathology. Although current treatments provide dramatic motor benefit in PD, they fail to alleviate some aspects of gait impairment and non-motor symptoms and may exacerbate cognitive and psychiatric features. To develop more personalized interventions to treat, forestall or prevent these features, more information regarding PD subtypes is necessary for patient selection and stratification, predicting progression, and evaluation of novel treatments. Therefore, we propose to examine the clinical and prognostic utility of PD subtypes and their stability through longitudinal behavioral assessments; determine the biological markers of PD subtypes from multimodal neuroimaging, CSF, and brain autopsy data; and translate the PD subtypes to a clinical setting.