imaging and genetic biomarkers of parkinson disease (pd) onset and progression in high-risk families

Conditions: Parkinson Disease; Parkinsonian Syndrome

Summary: parkinson's disease (pd) is a progressive neurodegenerative disorder characterized by rigidity, bradykinesia, postural instability, and tremor. clinical decline reflects ongoing degeneration of dopamine-containing neurons. a critical unmet need for clinical research is to improve early detection of these diseases by developing tools to assist with earlier diagnosis. biomarkers are broadly defined as characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (biomarkers defintions working group 2001). development of reliable biomarkers for pd would dramatically accelerate research on pd etiology, pathophysiology, disease progression and therapeutics. specific biomarkers may be useful at the onset of neurodegeneration, the onset of disease, and/or to mark disease progression. the biomarkers in this study include brain imaging with a radioactively labelled drug (beta-cit), computerized testing of memory, attention, motor speed, judgment and handwriting, and assessments of speech and smell. subjects may also be asked to provide a blood sample for genetic and biochemical testing.

individuals who agree to participate in this trial will have a complete screening exam by a neurologist at the institute for neurodegenerative disorders (ind) in new haven, ct. the exam may include blood tests, urine tests and an electrocardiogram (ecg -tracing of the electrical activity of the heart) to determine eligibility for the trial. research subjects will participate in a variety of biomarker assessments including brain imaging, which will take place over a period of two days. on the first day subjects report to ind after a brief exam subjects will receive a standard dose of lugol's solution (potassium iodide) by mouth to decrease uptake of the radioactive drug into the thyroid gland. subjects will be given a standard dose of potassium perchlorate if allergic to iodine. next subjects will receive the intravenous (iv - into a vein) injection of the beta-cit, a radioactive material that localizes in the brain. on the second day, about 24 hours after the injection, subjects will return to ind for a spect scan. the spect camera takes a "picture" of the radiation emitted by the beta-cit. this procedure will take approximately 30 minutes. subjects will be contacted by phone one week following the injection to monitor adverse (bad or harmful) events possibly related to the imaging procedure. this two-day imaging procedure, comprehensive neurological testing, and blood collection for genetics and biochemical testing may be repeated every 12 to 18 months during the next five years.

Eligibility criteria:
inclusion criteria: * age \>21 * previous participation in the progeni or core pd clinical study * a diagnosis of parkinsonism or a family history of parkinsonism * normal screening laboratory studies including: * complete blood count * chemistries * urinalysis exclusion criteria: * pregnancy * psychiatric disease other than history of depression * significant medical disease including abnormalities on screening biochemical or hematological labs or abnormal ecg.

Keywords: parkinson family history diagnosis