Study Rationale: This project seeks to validate three magnetic resonance imaging biomarkers capable of detecting and monitoring the degeneration of neurons in the substantia nigra in Parkinson’s disease. These biomarkers measure neuromelanin concentration, a pigment present in degenerating neurons of the substantia nigra, iron and the diffusion of water in tissues.
Hypothesis: We will characterize baseline and longitudinal changes of these biomarkers, determine the best way to measure them, design and validate machine learning methods that can predict the evolution of patients using baseline data, and calculate the number of persons needed to detect 1-year changes in a drug trial.
Study Design: We will retrospectively analyze datasets of several prospective research studies from six research centers (Canada, Netherlands, Israel, Australia, Germany and France) and the PPMI study. The database includes 1571 participants with Parkinson’s disease and 635 healthy control participants followed over 1 to 4 years. Participants had extensive clinical, genetics and imaging examinations including the three biomarkers.
Impact on Diagnosis/Treatment of Parkinson’s disease: We expect that these biomarkers will be useful for the diagnosis and monitoring of neurodegeneration during the progression of the disease. They will also allow to characterize the effect of a treatment aimed at slowing neurodegeneration in therapeutic trials.
Next Steps for Development: This project will validate the use of these biomarkers as endpoints in a clinical trial and will be adapted for practical use in clinical routine.