Brain Glucose Metabolism Heterogeneity in Idiopathic REM Sleep Behavior Disorder and in Parkinson’s Disease

Article type: Research Article

Authors: Arnaldi, Dario^{a; *} | Meles, Sanne K.^b | Giuliani, Alessandro^c | Morbelli, Silvia^d | Renken, Remco J.^e | Janzen, Annette^f | The REMPET Study Group | Mayer, Geert^{f; g} | Jonsson, Cathrine^h | Oertel, Wolfgang H.^{f; i} | Nobili, Flavio^a | Leenders, Klaus L.^{b; 1} | Pagani, Marco^{j; k; l; 1}

Collaborators: Sittig-Wiegand, Elisabeth^f | Depboylu, Candan^f | Reetz, Kathrin^l | Overeem, Sebastiaan^m | Pijpers, Angelique^m | Reesink, Fransje E.^b | van Laar, Teus^b | Teune, Laura K.^b | Höffken, Helmutⁿ | Luster, Marcusⁿ | Timmermann, Lars^f | Kesper, Karl^o | Adriaanse, Sofie M.^p | Booij, Jan^p | Sambuceti, Gianmario^d | Girtler, Nicola^a

Affiliations: [a] Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [b] Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands | [c] Environment and Health Department Istituto Superiore di Sanità, Rome, Italy | [d] Department of Health Sciences (DISSAL), Nuclear Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino Genoa, Italy | [e] Department of Neuroscience, Neuroimaging Center, University of Groningen, The Netherlands | [f] Department of Neurology, Philipps-Universität Marburg, Marburg, Germany | [g] Hephata Klinik, Schwalmstadt, Germany | [h] Medical Radiation Physics and Nuclear Medicine, Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden | [i] Institute for Neurogenomics, Helmholtz Center for Health and Environment, München, Germany | [j] Institutes of Cognitive Sciences and Technologies, CNR, Rome, Italy | [k] Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden | [l] Department of Nuclear Medicine, University of Groningen, University Medical Center Groningen, The Netherlands Department of Neurology and JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Aachen University, Aachen, Germany | [m] Kempenhaeghe Foundation, Sleep Medicine Centre, Heeze, The Netherlands | [n] Department of Nuclear Medicine, Philipps-Universität Marburg, Marburg, Germany | [o] Department of Internal Medicine, Section Respiratory Diseases, Philipps Universität Marburg, Marburg, Germany | [p] Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands

Correspondence: [*] Correspondence to: Dario Arnaldi, Department of Neuroscience (DINOGMI), Clinical Neurology, Largo P. Daneo 3, Genoa, 16132, Italy. Tel.: +39 010 5552246; Fax: +39 010 5556893; E-mail: [email protected].

Note: [1] Shared last authorship.

Abstract: Background/Objective:Idiopathic REM sleep behavior disorder (iRBD) often precedes Parkinson’s disease (PD) and other alpha-synucleinopathies. The aim of the study is to investigate brain glucose metabolism of patients with RBD and PD by means of a multidimensional scaling approach, using18F-FDG-PET as a biomarker of synaptic function. Methods:Thirty-six iRBD patients (64.1±6.5 y, 32 M), 72 PD patients, and 79 controls (65.6±9.4 y, 53 M) underwent brain 18F-FDG-PET. PD patients were divided according to the absence (PD, 32 subjects; 68.4±8.5 y, 15 M) or presence (PDRBD, 40 subjects; 71.8±6.6 y, 29 M) of RBD. 18F-FDG-PET scans were used to independently discriminate subjects belonging to four categories: controls (RBD no, PD no), iRBD (RBD yes, PD no), PD (RBD no, PD yes) and PDRBD (RBD yes, PD yes). Results:The discriminant analysis was moderately accurate in identifying the correct category. This is because the model mostly confounds iRBD and PD, thus the intermediate classes. Indeed, iRBD, PD and PDRBD were progressively located at increasing distance from controls and are ordered along a single dimension (principal coordinate analysis) indicating the presence of a single flux of variation encompassing both RBD and PD conditions. Conclusion:Data-driven approach to brain 18F-FDG-PET showed only moderate discrimination between iRBD and PD patients, highlighting brain glucose metabolism heterogeneity among such patients. iRBD should be considered as a marker of an ongoing condition that may be picked-up in different stages across patients and thus express different brain imaging features and likely different clinical trajectories.

Keywords: REM sleep behavior disorder, Parkinson’s disease, ¹⁸F-FDG-PET, synucleinopathy

DOI: 10.3233/JPD-181468

Journal: Journal of Parkinson's Disease, vol. 9, no. 1, pp. 229-239, 2019