Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder

Xianhua Han; Ping Wu; Ian Alberts; Hucheng Zhou; Huan Yu; Panagiotis Bargiotas; Igor Yakushev; Jian Wang; Guenter Höglinger; Stefan Förster; Claudio Bassetti; Wolfgang Oertel; Markus Schwaiger; Sung-Cheng Huang; Paul Cumming; Axel Rominger; Jiehui Jiang; Chuantao Zuo; Kuangyu Shi

doi:10.1016/j.nicl.2020.102294

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder

Neuroimage Clin. 2020:27:102294. doi: 10.1016/j.nicl.2020.102294. Epub 2020 May 26.

Authors

Xianhua Han¹, Ping Wu¹, Ian Alberts², Hucheng Zhou³, Huan Yu⁴, Panagiotis Bargiotas⁵, Igor Yakushev⁶, Jian Wang⁴, Guenter Höglinger⁷, Stefan Förster⁸, Claudio Bassetti⁹, Wolfgang Oertel¹⁰, Markus Schwaiger¹¹, Sung-Cheng Huang¹², Paul Cumming¹³, Axel Rominger², Jiehui Jiang¹⁴, Chuantao Zuo¹⁵, Kuangyu Shi¹⁶

Affiliations

¹ PET Center, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Nuclear Medicine, University of Bern, Switzerland.
³ Key Laboratory of Specialty Fiber Optics and Optical Access Networks, Joint International Research Laboratory of Specialty Fiber Optics and Advanced Communication ,Shanghai Institute for Advanced Communication and Data Science, Shanghai University, Shanghai, China.
⁴ Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
⁵ Department of Neurology, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland; Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
⁶ Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
⁷ Department of Neurology, Hannover Medical School, Germany.
⁸ Department of Nuclear Medicine, Technische Universität München, Munich, Germany; Department of Nuclear Medicine, Klinikum Bayreuth, Germany.
⁹ Department of Neurology, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland.
¹⁰ Department of Neurology, University of Marburg, Germany.
¹¹ Klinikum r. d. Isar, Technische Universität München, Munich, Germany.
¹² Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, USA.
¹³ Department of Nuclear Medicine, University of Bern, Switzerland; School of Psychology and Counselling and IHBI, Queensland University of Technology, Brisbane, Australia.
¹⁴ Key Laboratory of Specialty Fiber Optics and Optical Access Networks, Joint International Research Laboratory of Specialty Fiber Optics and Advanced Communication ,Shanghai Institute for Advanced Communication and Data Science, Shanghai University, Shanghai, China. Electronic address: jiangjiehui@shu.edu.cn.
¹⁵ PET Center, Huashan Hospital, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China. Electronic address: zuochuantao@fudan.edu.cn.
¹⁶ Department of Nuclear Medicine, University of Bern, Switzerland; Dept. Informatics, Technische Universität München, Munich, Germany.

Abstract

Objective: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson's disease (PD). Positron emission tomography (PET) with ¹⁸F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study.

Methods: 19 iRBD patients, 38 PD patients and 19 HC subjects underwent ¹⁸F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between ¹⁸F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between ¹⁸F-FDG uptake and the Unified Parkinson's Disease Rating Scale motor (UPDRS III) scores in the PD group.

Results: PD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative ¹⁸F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores.

Conclusion: Cerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

Keywords: Conversion; FDG; PET; Parkinson’s disease; REM sleep behavior disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Brain / metabolism*
Brain / pathology*
Brain / physiopathology
Cross-Sectional Studies
Disease Progression
Female
Humans
Image Processing, Computer-Assisted* / methods
Longitudinal Studies
Male
Middle Aged
Neuroimaging / methods
Parkinson Disease / metabolism
Parkinson Disease / physiopathology
Positron-Emission Tomography / methods
Prodromal Symptoms
Sleep Wake Disorders / metabolism*
Sleep Wake Disorders / pathology*