• INCLUSION CRITERIA:

Individuals with one or more of the following characteristics will be considered to be at risk and eligible for entering the Screening Examination phase. Priority will go to those with multiple risk factors. Subjects with at least 3 of the 4 risk factors will be invited to the Screening Examination. Control subjects will have none of these characteristics:

1. Genetic risk is assessed at the time of the Screening Examination in two ways-by creation of a pedigree and by genotyping. The pedigree shows diagrammatically the family history with respect to Parkinson disease. Genotyping is by DNA extraction and analysis for mutations of the LRRK2 or the alpha-synuclein gene or for alpha-synuclein gene replication. Either a positive family history (one or more immediate family members with PD) or positive DNA test results (LRRK2 or alpha-synuclein) satisfy the risk factor criterion for genetic risk. Other DNA analyses may be done subsequently; however, those results will not be considered relevant to genetic risk at the time of entry.
2. Olfactory Dysfunction is identified by the UPSIT. Decreased olfactory function, as indicated by less than a normal score, satisfies this risk factor criterion. In the event of a medical history indicating a secondary cause of decreased olfaction, decreased olfactory function as measured by the UPSIT is not be taken as satisfying this risk factor criterion.
3. REM Behavior Disorder (RBD) is identified by a history of sleep-related, injurious, potentially injurious, or disruptive behaviors (i.e., dream enactment behavior). Although polysomnographic evidence of REM sleep without atonia is a supportive clinical laboratory finding, the occurrence of these sleep-related abnormal behaviors is considered necessary and sufficient to satisfy the risk factor criterion. To satisfy the risk factor criterion, the individual must have movements of the body or limbs associated with dreaming and at least one of the following: potentially harmful sleep behavior, dreams that appear to be acted out, and sleep behavior that disrupts sleep continuity.
4. Orthostatic Hypotension is assessed by measurement of the blood pressure after the subject has been supine at rest for at least 15 minutes and then after the subject has stood upright for 5 minutes. A fall in systolic pressure of 20 mm Hg or more and a fall in diastolic pressure of 10 mm Hg or more at the time of the Screening Examination satisfy this risk factor criterion.

EXCLUSION CRITERIA:

1. Age - People younger than 18 years old or older than 70 years old are excluded.
2. Risk - A candidate subject is excluded if, in the judgment of the Principal Investigator, Protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator, the medical risk outweighs the potential scientific benefit.
3. Disqualifying Conditions - A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are insulin-dependent diabetes, hepatic or renal failure, symptomatic congestive heart failure, severe anemia, psychosis, ventricular arrhythmias, and symptomatic coronary heart disease. Persons with dementia interfering with their ability to provide informed consent are excluded. If dementia is suspected, such as by score on the mini-mental status examination of less than 24, then a bioethics consult will be obtained. If a subject develops dementia during the study, with a mini-mental score less than 24, the subject is excluded from further participation in the study. Persons who are unable to undergo MRI safely, due to implanted metal, are excluded.
4. Medications - A candidate subject is excluded if clinical considerations require continued treatment with a drug likely to interfere with the scientific results. Chronic, ongoing use of drugs such as tricyclic antidepressants that affect the clinical laboratory results exclude candidate subjects. People with known or suspected allergy or hypersensitivity to any test drug are excluded. Candidate subjects are not to discontinue any medications before discussion with the Principal Investigator, Research Nurse, Nurse Practitioner, or Clinical Fellow. If it is decided that discontinuing medications would be unsafe, then the subject is excluded from the study.
5. Herbal Medicines and Dietary Supplements - If a subject wishes to continue herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subject may participate, at the discretion of Principal Investigator
6. Practical Limitations - People in whom we feel it would be difficult to insert a catheter into a vein may be excluded. People who are not expected clinically to tolerate lying still supine during the testing may be excluded. People also may be excluded if they cannot tolerate having an MRI or having a lumbar puncture.
7. Pregnancy - Pregnant or lactating women are excluded. Women of childbearing potential must have a negative urine or blood test for pregnancy done within 24 hours before any testing involving radioactivity.