title: Imaging prodromal Parkinson disease: the Parkinson Associated Risk Syndrome Study.
abstract: OBJECTIVE
  The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD).
  
  
  METHODS
  In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [(123)I]β-CIT striatal binding ratio in hyposmic and normosmic subjects.
  
  
  RESULTS
  Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%.
  
  
  CONCLUSIONS
  Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD.
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA. djennings@indd.org.
authors.forename: Danna
authors.initials: D
authors.lastname: Jennings
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Stern
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Eberly
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: David
authors.initials: D
authors.lastname: Oakes
authors.affiliation: From the Institute for Neurodegenerative Disorders (D.J., J.S., K.M.), New Haven, CT; Parkinson's Disease and Movement Disorders Center (M.S.), Department of Neurology, University of Pennsylvania, Philadelphia; Department of Biostatistics and Computational Biology (S.E., D.O.), University of Rochester, NY; and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
mesh_terms: D000368:Aged; D003042:Cocaine / Q000031:analogs & derivatives; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D000857:Olfaction Disorders / Q000175:diagnosis / Q000209:etiology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D062706:Prodromal Symptoms; D019275:Radiopharmaceuticals; D012307:Risk Factors; D057566:Self Report; D011795:Surveys and Questionnaires; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine