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

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.

Longitudinal Network Changes and Phenoconversion Risk in Isolated REM Sleep Behavior Disorder

“…In that regard, FPCIT PET provides complementary information concerning the evolution of dopaminergic de cits in iRBD and the relationship of these changes to the onset of parkinsonism 23 . While presynaptic dopaminergic de cits, particularly those localized to the putamen, are a recognized risk factor for phenoconversion 12,24 , these measurements, as well as other potential predictors such as severity of motor symptoms, autonomic dysfunction, and cerebrospinal uid analysis, do not accurately foretell subsequent transition to clinically manifest PD 25,26 . That said, the longitudinal PET data presented in this study suggest that changes in PDRP expression and putamen DAT binding, when evaluated together, may predict phenoconversion more accurately than either measure alone.…”

Investigating the aspect of asymmetry in brain-first versus body-first Parkinson’s disease

“…It is theoretically possible that PDRBD− patients would have been more asymmetric than PDRBD+ cases had both groups been scanned at an earlier disease stage. Longitudinal data of 18 F-FDG PET and DAT SPECT scans will become available in an ongoing longitudinal study of RBD patients 39 . However, the prodromal stage of PDRBD− is ill-defined, and it would be challenging to identify such subjects in the general population.…”