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

Abstract

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. 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. 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. 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.