Objective: The aim of this study was to investigate whether midbrain hypometabolism can already be detected in iRBD patients using [18F]-FDG PET scans.

Background: Parkinson’s disease (PD) is typically diagnosed only after characteristic motor symptoms appear, at which point roughly 60 % of the dopaminergic neurons in the substantia nigra have already degenerated. Years to decades before idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) can already occur in the prodromal stage and is associated with a high risk of developing PD. In [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET) studies, a hypometabolic midbrain cluster has been described in PD patients that correlates with motor symptom progression and allows highly sensitive identification of PD [1–3]. Whether this hypometabolism is already present in iRBD patients remains unknown.

Method: [18F]-FDG PET scans from 51 PD patients, 16 healthy controls (HC), and 30 iRBD patients were analyzed, of whom 14 received a follow-up after an average of 3.9 years. After preprocessing in SPM12 (reorientation, normalization to MNI space, smoothing with 8 mm FWHM), intensity normalization to the pons was performed. FDG uptake values were extracted from the data-driven midbrain cluster [1] using MarsBaR and compared between groups in RStudio. In addition, changes between baseline and follow-up in the iRBD patients were examined. For validation, the analyses were repeated using a larger midbrain region from the TD atlas.

Results: IRBD patients showed hypometabolism compared to HC in both the data-driven (p = 0.00021, r = 0.59) and atlas ROI (p = 0.018, r = 0.41) and did not differ significantly from PD patients. In line with the previous study a hypometabolism in the data-driven midbrain cluster in PD could be found (p = 0.00046, r = 0.46). Longitudinal analysis in iRBD patients showed a significant decrease in FDG uptake in the atlas ROI (p = 0.021, r = 0.55), with individual analyses indicating more frequent decreases than increases in both ROIs. Notably, the two patients who phenoconverted to PD showed a pronounced decline.

Conclusion: These findings support the potential of midbrain metabolism as a biomarker for the early detection of nigral degeneration in prodromal stages of PD.

References: 1. Ruppert MC, Greuel A, Tahmasian M, Schwartz F, Stürmer S, Maier F, Hammes J, Tittgemeyer M, Timmermann L, van Eimeren T, Drzezga A, Eggers C (2020) Network degeneration in Parkinson’s disease: multimodal imaging of nigro-striato-cortical dysfunction. Brain 143(3):944–959. doi:10.1093/brain/awaa019
2. Ruppert-Junck MC, Kräling G, Greuel A, Tittgemeyer M, Timmermann L, Drzezga A, Eggers C, Pedrosa D (2024) Random forest analysis of midbrain hypometabolism using 18F-FDG PET identifies Parkinson’s disease at the subject-level. Front. Comput. Neurosci. 18:1328699. doi:10.3389/fncom.2024.1328699
3. Steidel K, Ruppert MC, Greuel A, Tahmasian M, Maier F, Hammes J, van Eimeren T, Timmermann L, Tittgemeyer M, Drzezga A, Pedrosa DJ, Eggers C (2022) Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease. npj Parkinsons Dis. 8(1):79. doi:10.1038/s41531-022-00341-8

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MDS Abstracts - https://www.mdsabstracts.org/abstract/midbrain-hypometabolism-in-idiopathic-rem-sleep-behavior-disorder-detected-by-18f-fdg-pet-as-a-potential-biomarker-of-nigral-degeneration/