Funded Studies
Objective/Rationale:
Ashkenazi Jewish PD patients in Israel have a 14% chance of carrying the G2019S LRRK2 mutation and 18% of carrying mutations in the GBA gene. Little is known on the association between these mutations and the pre-synaptic dopaminergic system or the brain metabolic activity. We aim to investigate the genetic and clinical manifestation of patients with parkinsonism who underwent DaT scan+ FDG PET to examine the relationships between clinical symptoms, brain metabolism and the pre-synaptic dopaminergic system while exploring the added value of FDG PET in the prediction of the clinical course in early parkinsonism.
Project Description:
Over the past 5 years, approximately 70 patients with early stages of parkinsonism underwent DaT Scan and FDG PET at the Tel-Aviv Medical Center as part of their initial diagnostic work-up. At the time of neuro-imaging, only a partial clinical evaluation was performed. Patients who underwent the two scans will be invited to participate in the study. After signing an informed consent, all patients will undergo a thorough neurological evaluation as well as assessment of cognition, autonomic function and smell identification ability. In addition DNA and RNA will be collected via blood sample to assess genetic status and expression in peripheral blood. Evaluations will take be undertaken by an experienced clinician, either at the hospital or at patients’ homes. Data collected will be transferred to the Department of Nuclear Medicine at Yale University for analysis.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
There is limited information in the literature about the association between known mutations in the LRRK2 and GBA genes and the pre-synaptic dopaminergic system and whole brain metabolic activity mainly because most studies reported on very small samples of patients and rarely used FDG-PET. Therefore the information that will be gathered in this study can enhance our understanding of the relationship between genetic status and brain activity in early stages of parkinsonism.
Anticipated Outcome:
The study uses a combination of two scanning techniques (DaT scan + FDG-PET) in the early stages of PD. This valuable information could enhance our understanding of brain metabolic activity in early stages of parkinsonism; explore the predictive value of the combined scans in the diagnosis, disease progression and clinical course of PD. In addition, the relatively high percentage of possible carriers of mutations known to increase the risk of PD will provide invaluable information about the relationships between brain metabolic activity, phenotype and genetic status.