Brain Imaging in RBD

Kogan, Rosalie V.; Meles, Sanne K.; Leenders, Klaus L.; Reetz, Kathrin; Oertel, Wolfgang H.

doi:10.1007/978-3-319-90152-7_30

Rapid-Eye-Movement Sleep Behavior Disorder 2018

DOI: 10.1007/978-3-319-90152-7_30

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Brain Imaging in RBD

Rosalie V. Kogan

Sanne K. Meles

Klaus L. Leenders

et al.

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Cited by 3 publications

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“… 16 PDRP is also expressed in iRBD patients at baseline, and it has been proved to increase over time and it is associated with phenoconversion. 14 , 17 , 18 However, PDRP has been identified in PD patients regardless of the presence/absence of RBD. To evaluate disease progression in RBD patients, it might be more useful to use a pattern identified in PD patients with RBD.…”

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confidence: 98%

“…Regarding the PD‐related pattern (PDRP), 15 it has been shown that pattern expression increases with disease progression and decreases with effective therapy 16 . PDRP is also expressed in iRBD patients at baseline, and it has been proved to increase over time and it is associated with phenoconversion 14,17,18 . However, PDRP has been identified in PD patients regardless of the presence/absence of RBD.…”

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confidence: 99%

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Derivation and Validation of a Phenoconversion‐Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder

et al. 2022

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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. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Derivation and Validation of a Phenoconversion‐Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder

et al. 2022

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

Carli

Meles

Janzen

et al. 2023

Eur J Nucl Med Mol Imaging

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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.

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Circuit imaging biomarkers in preclinical and prodromal Parkinson's disease

Meles

Oertel

Leenders

2021

Mol Med

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Parkinson’s disease (PD) commences several years before the onset of motor features. Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Two categories of patients are ideal to study the early disease stages. Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents a well-known prodromal stage of PD in which pathology is presumed to have reached the lower brainstem. The majority of patients with iRBD will develop manifest PD within years to decades. Another category encompasses non-manifest mutation carriers, i.e. subjects without symptoms, but with a known mutation or genetic variant which gives an increased risk of developing PD. The speed of progression from preclinical or prodromal to full clinical stages varies among patients and cannot be reliably predicted on the individual level. Clinical trials will require inclusion of patients with a predictable conversion within a limited time window. Biomarkers are necessary that can confirm pre-motor PD status and can provide information regarding lead time and speed of progression. Neuroimaging changes occur early in the disease process and may provide such a biomarker. Studies have focused on radiotracer imaging of the dopaminergic nigrostriatal system, which can be assessed with dopamine transporter (DAT) single photon emission computed tomography (SPECT). Loss of DAT binding represents an effect of irreversible structural damage to the nigrostriatal system. This marker can be used to monitor disease progression and identify individuals at specific risk for phenoconversion. However, it is known that changes in neuronal activity precede structural changes. Functional neuro-imaging techniques, such as 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (18F-FDG PET) and functional magnetic resonance imaging (fMRI), can be used to model the effects of disease on brain networks when combined with advanced analytical methods. Because these changes occur early in the disease process, functional imaging studies are of particular interest in prodromal PD diagnosis. In addition, fMRI and 18F-FDG PET may be able to predict a specific future phenotype in prodromal cohorts, which is not possible with DAT SPECT. The goal of the current review is to discuss the network-level brain changes in pre-motor PD.

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Brain Imaging in RBD

Cited by 3 publications

References 149 publications

Derivation and Validation of a Phenoconversion‐Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder

Derivation and Validation of a Phenoconversion‐Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder

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

Circuit imaging biomarkers in preclinical and prodromal Parkinson's disease

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