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Derivation and Validation of a Phenoconversion-Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder |
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| Authors: | Pietro Mattioli MD Beatrice Orso PsyD Claudio Liguori MD PhD Francesco Famà BSc Laura Giorgetti BSc Andrea Donniaquio MD Federico Massa MD Andrea Giberti MD David Vállez García PhD Sanne K. Meles MD PhD Klaus L. Leenders MD PhD Fabio Placidi MD PhD Matteo Spanetta Med Tech Agostino Chiaravalloti MD PhD Riccardo Camedda MD Orazio Schillaci MD Francesca Izzi MD Nicola B. Mercuri MD Matteo Pardini MD PhD Matteo Bauckneht MD PhD Silvia Morbelli MD PhD Flavio Nobili MD Dario Arnaldi MD PhD |
| Affiliation: | 1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Clinical Neurology, University of Genoa, Genoa, Italy;2. Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy;3. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Clinical Neurology, University of Genoa, Genoa, Italy IRCCS Ospedale Policlinico S. Martino, Genoa, Italy;4. IRCCS Ospedale Policlinico S. Martino, Genoa, Italy;5. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VuMC, Amsterdam Neuroscience, Amsterdam, The Netherlands;6. Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;7. Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;8. Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy Sleep Medicine Center, Neurology Unit, University Hospital “Tor Vergata”, Rome, Italy;9. Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy IRCCS Neuromed, Pozzilli, Italy;10. Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy;11. Sleep Medicine Center, Neurology Unit, University Hospital “Tor Vergata”, Rome, Italy;12. Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy IRCCS Fondazione Santa Lucia, Rome, Italy;13. IRCCS Ospedale Policlinico S. Martino, Genoa, Italy Department of Health Science (DISSAL), University of Genoa, Genoa, Italy |
| Abstract: | BackgroundIdiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion.ObjectiveThe aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analysis (Scaled Subprofile Model and Principal Component Analysis [SSM-PCA]).MethodsSeventy-six consecutive iRBD patients (70 ± 6 years, 15 women) were enrolled in two centers and prospectively evaluated to assess phenoconversion (30 converters, 73 ± 6 years, 14 Parkinson's disease and 16 dementia with Lewy bodies, follow-up time: 21 ± 14 months; 46 nonconverters, 69 ± 6 years, follow-up time: 33 ± 19 months). All patients underwent [18F]FDG-PET (18F-fluorodeoxyglucose positron emitting tomography) to investigate brain glucose metabolism at baseline. SSM-PCA was applied to obtain the iRBDconvRP; nonconverter patients were considered as the reference group. Survival analysis and Cox regression were applied to explore prediction power.ResultsFirst, we derived and validated two distinct center-specific iRBDconvRP that were comparable and significantly able to predict phenoconversion. Then, SSM-PCA was applied to the whole set, identifying the iRBDconvRP. The iRBDconvRP included positive voxel weights in cerebellum; brainstem; anterior cingulate cortex; lentiform nucleus; and middle, mesial temporal, and postcentral areas. Negative voxel weights were found in posterior cingulate, precuneus, middle frontal gyrus, and parietal areas. Receiver operating characteristic analysis showed an area under the curve of 0.85 (sensitivity: 87%, specificity: 72%), discriminating converters from nonconverters. The iRBDconvRP significantly predicted phenoconversion (hazard ratio: 7.42, 95% confidence interval: 2.6–21.4).ConclusionsWe derived and validated an iRBDconvRP to efficiently discriminate converter from nonconverter iRBD patients. [18F]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. |
| Keywords: | rapid eye movement sleep behavior disorder fluorodeoxyglucose positron emitting tomography α-synucleinopathy phenoconversion disease-related pattern |