Occipital hypometabolism is a risk factor for conversion to Parkinson's disease in isolated REM sleep behaviour disorder

Giulia Carli; Sanne K Meles; Annette Janzen; Elisabeth Sittig; Rosalie V Kogan; Daniela Perani; Wolfgang H Oertel; Klaus L Leenders; REMPET Working Group

doi:10.1007/s00259-023-06289-y

Occipital hypometabolism is a risk factor for conversion to Parkinson's disease in isolated REM sleep behaviour disorder

Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3290-3301. doi: 10.1007/s00259-023-06289-y. Epub 2023 Jun 13.

Authors

Giulia Carli¹, Sanne K Meles², Annette Janzen³, Elisabeth Sittig³, Rosalie V Kogan^{4

5}, Daniela Perani^{6

7}, Wolfgang H Oertel^{3

8}, Klaus L Leenders^{4

2}; REMPET Working Group

Affiliations

¹ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. g.carli@umcg.nl.
² Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Neurology, Philipps-Universität Marburg, Marburg, Germany.
⁴ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Internal Medicine, Sierra View Medical Center, Porterville, CA, USA.
⁶ School of Psychology, Vita-Salute San Raffaele University, Milan, Italy.
⁷ In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁸ Institute for Neurogenomics, Helmholtz Center for Health and Environment, Munich, Germany.

Abstract

Purpose: Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with ¹⁸F-FDG PET in iRBD is promising, but longitudinal studies are scarce. We investigated the regional brain changes in iRBD over time, related to phenoconversion.

Methods: Twenty iRBD patients underwent two consecutive ¹⁸F-FDG PET brain scans and clinical assessments (3.7 ± 0.6 years apart). Seventeen patients also underwent ¹²³I-MIBG and ¹²³I-FP-CIT SPECT scans at baseline. Four subjects phenoconverted to Parkinson's disease (PD) during follow-up. ¹⁸F-FDG PET scans were compared to controls with a voxel-wise single-subject procedure. The relationship between regional brain changes in metabolism and PD-related pattern scores (PDRP) was investigated.

Results: Individual hypometabolism t-maps revealed three scenarios: (1) normal ¹⁸F-FDG PET scans at baseline and follow-up (N = 10); (2) normal scans at baseline but occipital or occipito-parietal hypometabolism at follow-up (N = 4); (3) occipital hypometabolism at baseline and follow-up (N = 6). All patients in the last group had pathological ¹²³I-MIBG and ¹²³I-FP-CIT SPECT. iRBD converters (N = 4) showed occipital hypometabolism at baseline (third scenario). At the group level, hypometabolism in the frontal and occipito-parietal regions and hypermetabolism in the cerebellum and limbic regions were progressive over time. PDRP z-scores increased over time (0.54 ± 0.36 per year). PDRP expression was driven by occipital hypometabolism and cerebellar hypermetabolism.

Conclusions: Our results suggest that occipital hypometabolism at baseline in iRBD implies a short-term conversion to PD. This might help in stratification strategies for disease-modifying trials.

Keywords: 18F-FDG PET; Isolated REM sleep behaviour disorder; Occipital hypometabolism; Short-term conversion.

MeSH terms

3-Iodobenzylguanidine
Fluorodeoxyglucose F18
Humans
Parkinson Disease* / diagnostic imaging
Parkinson Disease* / metabolism
Positron-Emission Tomography / methods
REM Sleep Behavior Disorder* / diagnostic imaging
REM Sleep Behavior Disorder* / metabolism
Risk Factors

Substances

2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
Iodine-123
Fluorodeoxyglucose F18
3-Iodobenzylguanidine