FDG PET Parkinson’s disease-related pattern as a biomarker for clinical trials in early stage disease

Abstract

Background: The development of therapeutic interventions for Parkinson disease (PD) is challenged by disease complexity and subjectivity of symptom evaluation. A Parkinson's Disease Related Pattern (PDRP) of glucose metabolism via fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to correlate with motor symptom scores and may aid the detection of disease-modifying therapeutic effects. Objectives: We sought to independently evaluate the potential utility of the PDRP as a biomarker for clinical trials of early-stage PD. Methods: Two machine learning approaches (Scaled Subprofile Model (SSM) and NPAIRS with Canonical Variates Analysis) were performed on FDG-PET scans from 17 healthy controls (HC) and 23 PD patients. The approaches were compared regarding discrimination of HC from PD and relationship to motor symptoms. Results: Both classifiers discriminated HC from PD (p < 0.01, p < 0.03), and classifier scores for age- and gender- matched HC and PD correlated with Hoehn & Yahr stage (R2 = 0.24, p < 0.015) and UPDRS (R2 = 0.23, p < 0.018). Metabolic patterns were highly similar, with hypometabolism in parieto-occipital and prefrontal regions and hypermetabolism in cerebellum, pons, thalamus, paracentral gyrus, and lentiform nucleus relative to whole brain, consistent with the PDRP. An additional classifier was developed using only PD subjects, resulting in scores that correlated with UPDRS (R2 = 0.25, p < 0.02) and Hoehn & Yahr stage (R2 = 0.16, p < 0.06). Conclusions: Two independent analyses performed in a cohort of mild PD patients replicated key features of the PDRP, confirming that FDG-PET and multivariate classification can provide an objective, sensitive biomarker of disease stage with the potential to detect treatment effects on PD progression. Keywords: Parkinson, FDG PET, PDRP, Classifier, Biomarker