Objective/Rationale:
Imaging techniques such as DaT SPECT, FDG PET and magnetic resonance imaging (MRI) have frequently been used to assess Parkinson’s disease (PD) changes in parts of the brain called the cortex and subcortex. However, currently there is no marker to objectively measure the severity and rate of progression of cellular dysfunction and neurodegeneration in PD. This project aims to assess cortical and subcortical structures and neuronal integrity with a combined approach using different imaging techniques in recently diagnosed patients with PD (carriers and non-carriers of the G2019S mutation in the LRRK2 gene) and non-manifesting carriers (people who have the mutation but do not have PD).
Project Description:
This analysis will include available data from patients with PD carriers of the G2019S mutation and their first-degree relatives. Additional scans will be collected from recently diagnosed patients with PD (less than two years from diagnosis) and 20 control subjects. Imaging data will be processed and complemented by clinical data to study the relationships between structural and functional features and clinical signs and symptoms. This information is invaluable for understanding the differences between PD and normal aging and the contribution of LRRK2 mutations to cortical and subcortical involvement.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
It is crucial to understand changes in brain function that occur before overt symptoms of disease are detected. We believe we will be able to better identify those asymptomatic mutation carriers who are experiencing pre-motor and cognitive network dysfunctions and are at an increased risk of developing PD.
Anticipated Outcome:
We hypothesize that metabolic changes in both the motor and cognitive networks would be evident in recently diagnosed patients and these changes will be correlated with decreased DaT (dopamine active transporter) binding and with clinical scores. Furthermore we speculate that similar (although more subtle changes) will be observed in non-manifesting carriers, reflecting changes in the pre-diagnostic phase of the disease.