This study is designed as a prospective cohort study to test the strategy of combining two biomarkers of parkinsonism, olfaction and brain imaging with a radioactively labeled drug, [123I]β-CIT , in a population of first-degree relatives of PD patients as a tool to establish an 'at risk' Parkinson disease cohort without motor symptoms of PD. First-degree relatives of PD will be recruited through PD research sites and national foundations to participate in this study. In addition, first degree relatives of PD patients will be recruited directly through advertising.

First-degree relatives that agree to participate (n=3,000) will be asked to complete a 40-item olfactory identification test provided by mail. 300 subjects (225 with decreased odor identification and 75 with normal olfaction) will be invited to undergo DAT imaging at the Institute for Neurodegenerative Disorders in New Haven, CT. There will also be additional clinical follow-up at participant's clinical (local) site. The primary outcome measure for the study will be the mean striatal uptake of [123I]B-CIT in first-degree relatives with a loss of odor identification, which will be compared to an established healthy control database (age 40-70; n=50). 300 relatives will be followed longitudinally with clinical evaluations and a second imaging study completed after two years. Comparing the first and second scans in this subset of subjects will allow us to evaluate the rate of progressive loss in dopamine transporter density during this pre-symptomatic period.

At Risk - Inclusion Criteria:

• subject must have a first-degree relative with PD, based on their report
• subject must not carry a diagnosis of PD or other neurodegenerative disorder.
• subject must be either at least 50 yrs old or within 10 yrs of the age of onset of their affected relative
• Subject must have no other known reason for abnormal olfaction (e.g. nasal trauma, sinus infection, sinus surgery)
• Subject must not be pregnant if participating in the imaging portion of this study

Non-First Degree Relative - Inclusion Criteria:

• Subject must not carry a diagnosis of PD or other neurodegenerative disorders
• Subject must have no other known reason for abnormal olfaction (e.g. nasal trauma, sinus infection, sinus surgery)
• Subject must not be pregnant or be an actively nursing mother if participating in the imaging portion of this study.

Exclusion Criteria:

• diagnosis of PD or other neurodegenerative disorder
• other known reason for abnormal olfaction (e.g. nasal trauma, sinus infection, sinus surgery)
• pregnancy, if participating in the imaging portion of this study

Participants and Investigators were not provided results of the University of Pennsylvania Smell Identification Test (UPSIT).