@article{527bcf0439244aab95b1600f671ab37f,
title = "Clinical and Imaging Progression in the PARS Cohort: Long-Term Follow-up",
abstract = "BACKGROUND AND OBJECTIVES: The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression markers during the prodromal period.METHODS: Subjects with hyposmia completed annual clinical evaluations and biennial [ 123 I]{\ss}-CIT single-photon emission computed tomography scans. Subjects were categorized as normal (>80% age-expected tracer uptake; n = 134), indeterminate (>65-80%; n = 30), and dopamine transporter deficit (≤65%; n = 21) by their baseline scan, and survival analysis was used to compare risk of conversion to motor PD. Progressing to a scan with a dopamine transporter deficit was assessed for those subjects with either normal or indeterminate baseline imaging. RESULTS: Over a mean of 6.3 [standard deviation: 2.2] years of follow-up, 67% (n = 14) of dopamine transporter deficit subjects, 20% (n = 6) of dopamine transporter indeterminate subjects, and 4% (n = 6) of dopamine transporter normal subjects converted to a PD diagnosis (P < 0.0001). Among subjects without dopamine transporter deficit at baseline, a reduction to ≤65% age-expected uptake occurred in 12 of 30 (40%) with indeterminate dopamine transporter and 7 of 134 (5%) with no dopamine transporter DAT deficit (P < 0.0001). Imaging conversion during follow-up was associated with subsequent clinical conversion (hazard ratio: 9.6; P = 0.0157).DISCUSSION AND CONCLUSIONS: Long-term follow-up of the PARS cohort demonstrated a high rate of conversion to clinical PD in subjects who either had abnormal dopamine transporter imaging at baseline or developed abnormal imaging during follow-up. These data extend the earlier PARS findings and present new results showing the sequence of incident imaging deficit, imaging progression, and clinical changes that occur in prodromal PD. {\textcopyright} 2020 International Parkinson and Movement Disorder Society.",
keywords = "Parkinson's disease, biomarkers, dopamine transporter imaging, prodromal",
author = "Andrew Siderowf and Danna Jennings and Matthew Stern and John Seibyl and Shirley Eberly and David Oakes and Kenneth Marek and Danna Jennings and Ken Marek and John Seibyl and Andrew Siderowf and Matthew Stern and David Russell and Kapil Sethi and Samuel Frank and Tanya Simuni and Robert Hauser and Bernard Ravina and Irene Richards and Grace Liang and Charles Adler and Rachel Saunders-Pullman and Evatt, {Marian L.} and Eugene Lai and Indu Subramanian and Penelope Hogarth and Kathryn Chung",
note = "Funding Information: Dr. Siderowf has been a consultant to the following companies in the past year: Biogen, Voyager Therapeutics, Merck, Denali, Wave Life Sciences, and Prilenia Therapeutics. He has received grant funding from the Michael J. Fox Foundation and NINDS. Dr. Jennings is an employee of Denali Therapeutics Inc. Dr. Stern has been a consultant to Acorda, Acadia, Biogen, Revance, Alexion, Luye and Neuroderm. Dr. Seibyl has been a consultant to Roche, GE Healthcare, Piramal, and Bayer and is a cofounder of Molecular NeruoImaging and an owner of inviCRO. Ms. Eberly has received grant support from the Huntington Study Group on behalf of Auspex/Teva and from Biogen Idec and Vaccinex. Dr. Oakes has received research support from the National Institutes of Health, the U.S. Department of Defense, the Michael J. Fox Foundation, Vaccinex, Auspex/TEVA, and Prana Biotech. He has received personal compensation from Voyager Therapeutics and the University California for service on their data and safety monitoring boards and from Raptor Pharmaceuticals for personal consulting. Dr. Marek has been a Consultant for Pfizer, GE Healthcare, Merck, Lilly, BMS, Piramal, Prothena, Neurophage, nLife, and Roche and receives funding for the following grants: W81XWH‐06‐1‐0678 Establishing an “at risk” cohort for Parkinson Disease Neuroprevention using olfactory testing and DAT imaging, DOD, Investigator 10/1/06 to 09/30/15; Parkinson Progression Marker Initiative (PPMI), Michael J. Fox Foundation, Principal Investigator 6/15/09 to 6/14/18; DAT imaging in LRRK2 family members, the Michael J. Fox Foundation, Principal Investigator 1/15/10 to 1/14/15. Ownership in Molecular NeuroImaging, LLC. Funding Information: Dr. Siderowf has been a consultant to the following companies in the past year: Biogen, Voyager Therapeutics, Merck, Denali, Wave Life Sciences, and Prilenia Therapeutics. He has received grant funding from the Michael J. Fox Foundation and NINDS. Dr. Jennings is an employee of Denali Therapeutics Inc. Dr. Stern has been a consultant to Acorda, Acadia, Biogen, Revance, Alexion, Luye and Neuroderm. Dr. Seibyl has been a consultant to Roche, GE Healthcare, Piramal, and Bayer and is a cofounder of Molecular NeruoImaging and an owner of inviCRO. Ms. Eberly has received grant support from the Huntington Study Group on behalf of Auspex/Teva and from Biogen Idec and Vaccinex. Dr. Oakes has received research support from the National Institutes of Health, the U.S. Department of Defense, the Michael J. Fox Foundation, Vaccinex, Auspex/TEVA, and Prana Biotech. He has received personal compensation from Voyager Therapeutics and the University California for service on their data and safety monitoring boards and from Raptor Pharmaceuticals for personal consulting. Dr. Marek has been a Consultant for Pfizer, GE Healthcare, Merck, Lilly, BMS, Piramal, Prothena, Neurophage, nLife, and Roche and receives funding for the following grants: W81XWH-06-1-0678 Establishing an ?at risk? cohort for Parkinson Disease Neuroprevention using olfactory testing and DAT imaging, DOD, Investigator 10/1/06 to 09/30/15; Parkinson Progression Marker Initiative (PPMI), Michael J. Fox Foundation, Principal Investigator 6/15/09 to 6/14/18; DAT imaging in LRRK2 family members, the Michael J. Fox Foundation, Principal Investigator 1/15/10 to 1/14/15. Ownership in Molecular NeuroImaging, LLC. Funding Information: : Support for this study is provided by the Department of Defense award number W81XWH‐06‐067. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding agencies Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",
year = "2020",
month = sep,
day = "1",
doi = "10.1002/mds.28139",
language = "English (US)",
volume = "35",
pages = "1550--1557",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley & Sons Inc.",
number = "9",
}