Journal article
Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder
Annals of clinical and translational neurology, Vol.8(1), pp.201-212
01/2021
DOI: 10.1002/acn3.51269
PMCID: PMC7818144
PMID: 33321002
Abstract
Individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for a clinical diagnosis of an α-synucleinopathy (aSN). They could serve as a key population for disease-modifying trials. Abnormal dopamine transporter (DAT) imaging is a strong candidate biomarker for risk of aSN diagnosis in iRBD. Our primary objective was to identify a quantitative measure of DAT imaging that predicts diagnosis of clinically-defined aSN in iRBD.
The sample included individuals with iRBD, early Parkinson's Disease (PD), and healthy controls (HC) enrolled in the Parkinson Progression Marker Initiative, a longitudinal, observational, international, multicenter study. The iRBD cohort was enriched with individuals with abnormal DAT binding at baseline. Motor and nonmotor measures were compared across groups. DAT specific binding ratios (SBR) were used to calculate the percent of expected DAT binding for age and sex using normative data from HCs. Receiver operative characteristic analyses identified a baseline DAT binding cutoff that distinguishes iRBD participants diagnosed with an aSN in follow-up versus those not diagnosed.
The sample included 38 with iRBD, 205 with PD, and 92 HC who underwent DAT-SPECT at baseline. Over 4.7 years of mean follow-up, 14 (36.84%) with iRBD were clinically diagnosed with aSN. Risk of aSN diagnosis was significantly elevated among those with baseline putamen SBR ≤ 48% of that expected for age and sex, relative to those above this cutoff (hazard ratio = 17.8 [95%CI: 3.79-83.3], P = 0.0003).
We demonstrate the utility of DAT SBR to identify individuals with iRBD with increased short-term risk of an aSN diagnosis.
Details
- Title: Subtitle
- Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder
- Creators
- Lana M Chahine - Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USAMichael C Brumm - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAChelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAWolfgang Oertel - Department of Neurology, Philipps University, Marburg, GermanyBrit Mollenhauer - Paracelsus-Elena-Klinik, Kassel, GermanyAmy Amara - Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USAAna Fernandez-Arcos - Neurology Service, Hospital Clinic de Barcelona, Barcelona, SpainEduardo Tolosa - Neurology Service, Hospital Clinic de Barcelona, Barcelona, SpainCristina Simonet - Neurology Service, Hospital Clinic de Barcelona, Barcelona, SpainBirgit Hogl - Department of Neurology, Innsbruck Medical University, Innsbruck, AustriaAleksandar Videnovic - Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USASamantha J Hutten - The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USACaroline Tanner - Department of Neurology, University of California San Francisco, San Francisco, California, USADaniel Weintraub - Departments of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAElliot Burghardt - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAChristopher Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAHyunkeun R Cho - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAKarl Kieburtz - University of Rochester Medical Center, University of Rochester, Rochester, NY, USAKathleen L Poston - Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USAKalpana Merchant - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USADouglas Galasko - Department of Neurology, University of California, San Diego, California, USATatiana Foroud - Department of Medical & Molecular Genetics, Indiana University, Indianapolis, Indiana, USAAndrew Siderowf - Departments of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAKenneth Marek - Institute for Neurodegenerative Disorders, New Haven, Connecticut, USATanya Simuni - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USAAlex Iranzo - Neurology Service, Hospital Clinic de Barcelona, Barcelona, Spain
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.8(1), pp.201-212
- DOI
- 10.1002/acn3.51269
- PMID
- 33321002
- PMCID
- PMC7818144
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Grant note
- DOI: 10.13039/100000864, name: Michael J. Fox Foundation for Parkinson's Research
- Language
- English
- Date published
- 01/2021
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214955502771
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