Background <p>Isolated REM sleep behavior disorder (iRBD) is a prodromal stage of alpha-synucleinopathies. Biomarkers are crucial for predicting and monitoring its progression, warranting long-term neuroimaging studies. While the Parkinson's Disease Related Pattern (PDRP) from ¹⁸F-FDG PET is a recognized Parkinson's Disease (PD) biomarker, its role in tracking progression in prodromal PD remains unclear.</p> Objective <p>To explore PDRP expression across three time points using ¹⁸F-FDG PET over an 8-year follow-up in iRBD.</p> Methods <p>Thirteen iRBD subjects underwent ¹⁸F-FDG PET brain scans at baseline (BL), follow-up 1 (FU1, 4 years), and follow-up 2 (FU2, 8 years). Among them, four developed PD, one Dementia with Lewy Bodies (DLB), three showed subthreshold parkinsonism, and five showed no progression. PDRP z-scores were analyzed within and between groups (converters vs. non-converters) using a two-way repeated measures ANOVA. Similar analyses were conducted for motor scores (Unified Parkinson’s Disease Rating Scale part three, UPDRS-III).</p> Results <p>There was a significant main effect of group (<i>p</i> = 0.011), time (<i>p</i> &lt; 0.001), and a group*time interaction (<i>p</i> = 0.020), indicating that while PDRP z-scores increased over time in most iRBD subjects, the increase was more pronounced in converters (<i>n</i> = 5) than in non-converters (<i>n</i> = 8). Post-hoc tests revealed significantly higher PDRP z-scores in converters compared to non-converters at FU1 (<i>p</i> = 0.042) and FU2 (<i>p</i> = 0.024). For UPDRS-III scores we found significant effects of group (<i>p</i> = 0.011), time (<i>p</i> &lt; 0.001), and their interaction (<i>p</i> = 0.0003).</p> Conclusions <p>Repeated ¹⁸F-FDG PET scans may be useful to monitor prodromal disease progression and predict conversion in iRBD patients.</p>