1. Dopamine transporter imaging predicts clinically‐defined α‐synucleinopathy in REM sleep behavior disorder
- Author
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Aleksandar Videnovic, Hyunkeun Ryan Cho, Tanya Simuni, Wolfgang H. Oertel, Lana M. Chahine, Amy W. Amara, Cristina Simonet, Tatiana Foroud, Michael C. Brumm, Kenneth Marek, Elliot Burghardt, Brit Mollenhauer, Kathleen L. Poston, Alex Iranzo, Andrew Siderowf, Daniel Weintraub, Douglas Galasko, Samantha J. Hutten, Birgit Högl, Ana Fernández-Arcos, Kalpana Merchant, Chelsea Caspell-Garcia, Eduardo Tolosa, Karl Kieburtz, Christopher S. Coffey, and Caroline M. Tanner
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Synucleinopathies ,Population ,Rapid eye movement sleep ,REM Sleep Behavior Disorder ,REM sleep behavior disorder ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,education ,Research Articles ,Dopamine transporter ,Aged ,Tomography, Emission-Computed, Single-Photon ,education.field_of_study ,Dopamine Plasma Membrane Transport Proteins ,biology ,business.industry ,General Neuroscience ,Putamen ,Hazard ratio ,Middle Aged ,medicine.disease ,030104 developmental biology ,Cohort ,biology.protein ,Biomarker (medicine) ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Introduction 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. Methods 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. Results 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). Conclusion We demonstrate the utility of DAT SBR to identify individuals with iRBD with increased short‐term risk of an aSN diagnosis.
- Published
- 2020