TY - JOUR
T1 - Derivation and Validation of a Phenoconversion-Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder
AU - Mattioli, Pietro
AU - Orso, Beatrice
AU - Liguori, Claudio
AU - Famà, Francesco
AU - Giorgetti, Laura
AU - Donniaquio, Andrea
AU - Massa, Federico
AU - Giberti, Andrea
AU - Vállez García, David
AU - Meles, Sanne K.
AU - Leenders, Klaus L.
AU - Placidi, Fabio
AU - Spanetta, Matteo
AU - Chiaravallotti, Agostino
AU - Camedda, Riccardo
AU - Schillaci, Orazio
AU - Izzi, Francesca
AU - Mercuri, Nicola B.
AU - Pardini, Matteo
AU - Bauckneht, Matteo
AU - Morbelli, Silvia
AU - Nobili, Flavio
AU - Arnaldi, Dario
N1 - Funding Information: This study was partly supported by a grant from the Italian Ministry of Health to IRCCS Ospedale Policlinico San Martino (Fondi per la Ricerca Corrente 2019/2020, and Italian Neuroscience network [RIN]) and by a University of Genoa Curiosity Grant to M.P. This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (legge 232 del 2016). Funding agencies: Funding Information: M.P. received research support from Novartis and Nutricia and fees from Novartis, Merck, and Biogen. D.A. received fees from Fidia, Jazz, and Lundbeck for lectures, consultation, and board participation. S.M. received speaker honoraria from G.E. Healthcare. F.N. received fees from Bial for consultation, from G.E. Healthcare for teaching talks, and from Roche and Biogen for board participation. All other authors report no conflicts of interest. Relevant conflicts of interest/financial disclosures: Publisher Copyright: © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2022
Y1 - 2022
N2 - Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. Objective: The 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]). Methods: Seventy-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. Results: First, 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). Conclusions: We 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.
AB - Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. Objective: The 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]). Methods: Seventy-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. Results: First, 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). Conclusions: We 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.
KW - disease-related pattern
KW - fluorodeoxyglucose positron emitting tomography
KW - phenoconversion
KW - rapid eye movement sleep behavior disorder
KW - α-synucleinopathy
UR - http://www.scopus.com/inward/record.url?scp=85139208333&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/mds.29236
DO - https://doi.org/10.1002/mds.29236
M3 - Article
C2 - 36190111
SN - 0885-3185
JO - Movement disorders
JF - Movement disorders
ER -