Objective: To understand functional brain changes over time in isolated REM sleep behaviour disorder (iRBD), we investigated the progression of regional hypometabolism in iRBD patients using FDG PET at two-time points.

Background: iRBD is the prodromal stage of alpha-synucleinopathies. Patients with iRBD may be ideal candidates for future clinical trials, but biomarkers are needed to determine lead time and speed of progression. FDG-PET has shown promise as a neuroimaging biomarker in Parkinson’s disease (PD) and iRBD[1-2-3]. However, little is known about regional brain hypometabolic changes over time in iRBD[4].

Method: 20 patients with video-polysomnography confirmed iRBD underwent two FDG-PET brain scans ≈3.7 years apart, along with motor (UPDRS-III) and cognitive (MoCA) testing. Four subjects converted to PD at follow-up (iRBD-C). Each FDG-PET scan was compared to 69 controls with a statistical parametric mapping (SPM) procedure[5]. The resulting SPM t-maps were used to extract mean hypometabolism values from 121 Regions of Interest (ROIs) covering the whole brain. Average ROIs’ hypometabolism values were compared between baseline and follow-up and between iRBD-C and iRBD-non-converters (iRBD-NC). We also evaluated the relationship between regional hypometabolism and the expression of a previously identified whole-brain Parkinson’s disease-related pattern (PDRP)[1-2].

Results: At both time points, the iRBD-C showed significantly lower metabolism in occipito-parietal regions than iRBD-NC (calcarine cortex, lingual gyrus, superior, middle and inferior occipital giry and angular gyrus, bilaterally). The rate of hypometabolic decline (∆hypometabolism/year) in these brain regions correlated significantly with PDRP z-score changes (∆PDRP z-score/year) ranging from moderate to strong strength of correlation (r=0.428-0.809). ∆PDRP rate showed a significant positive correlation with the rate at which motor symptoms worsened (∆UPDRS-III/year)(p=0.013; r=0.556). Progressive hypometabolism in the left inferior occipital gyrus significantly correlated with MoCA score deterioration (∆MoCA/year) (p=0.030; r=0.499).

Conclusion: Progressive occipital hypometabolism is a characteristic of iRBD patients with a high risk of rapid (~4 years) progression to PD and is associated with cognitive decline. This finding is in line with disease progression in manifest PD to dementia.

References: [1] Meles, S. K., Vadasz, D., Renken, R. J., Sittig‐Wiegand, E., Mayer, G., Depboylu, C., … & Oertel, W. H. (2017). FDG PET, dopamine transporter SPECT, and olfaction: combining biomarkers in REM sleep behavior disorder. Movement Disorders, 32(10), 1482-1486.
[2] Kogan RV, Janzen A, Meles SK, Sittig E, Renken RJ, Gurvits V, Mayer G, Leenders KL, Oertel WH; REMPET (2021). Four-Year Follow-up of [18 F]Fluorodeoxyglucose Positron Emission Tomography-Based Parkinson’s Disease-Related Pattern Expression in 20 Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder Shows Prodromal Progression. Movement Disorders, 36(1), 230-235.
[3] Carli, G., Caminiti, S. P., Galbiati, A., Marelli, S., Casoni, F., Padovani, A., … & Perani, D. (2020). In‐vivo signatures of neurodegeneration in isolated rapid eye movement sleep behaviour disorder. European Journal of Neurology, 27(7), 1285-1295.
[4] Kim, R., Lee, J. Y., Kim, Y. K., Kim, H., Yoon, E. J., Shin, J. H., … & Jeon, B. (2021). Longitudinal Changes in Isolated Rapid Eye Movement Sleep Behavior Disorder‐Related Metabolic Pattern Expression. Movement Disorders, 36(8), 1889-1898.
[5] Perani, D., Della Rosa, P. A., Cerami, C., Gallivanone, F., Fallanca, F., Vanoli, E. G., … & EADC-PET Consortium. (2014). Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting. NeuroImage: Clinical, 6, 445-454.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-regional-hypometabolism-progression-in-irbd-the-cognitive-role-of-occipital-hypometabolism/