Objective: To determine whether baseline and longitudinal Parkinson’s disease–related pattern expression predicts conversion to Parkinson’s disease or dementia with Lewy bodies in idiopathic REM sleep behavior disorder.

Background: iRBD is a strong prodromal marker of synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), neurodegeneration-related metabolic changes can be detected. Spatial covariance analysis of FDG-PET has identified a Parkinson’s disease-related pattern (PDRP). PDRP expression is present in iRBD, with higher values and a more rapid increase in those who phenoconvert to PD or DLB, suggesting potential value as a biomarker for disease progression and prediction of phenoconversion. Validation in large multi-center samples is needed.

Method: In this multicenter longitudinal cohort, 289 individuals with iRBD underwent FDG-PET imaging, yielding 415 scans. PDRP expression was quantified as a z-score relative to healthy controls. Participants were clinically followed after their last scan to determine conversion to PD or DLB. Time-to-event analyses were performed using Cox proportional hazards models stratified by study center and adjusted for age. Baseline PDRP expression was evaluated as a predictor of conversion. A time-dependent Cox model assessed the association between longitudinal PDRP expression and conversion risk.

Results: During follow-up, 77/289 participants (26.6%) converted. Higher baseline PDRP expression was associated with increased conversion risk (HR 1.42 per SD increase, 95% CI 1.22–1.64, p<0.001). Older age was associated with higher conversion risk (HR 1.08 per year, 95% CI 1.03–1.14, p<0.001). Longitudinal PDRP expression remained significantly associated with conversion in the time-dependent model (HR 1.45 per SD increase, 95% CI 1.25–1.68, p<0.001). Kaplan–Meier analysis showed earlier phenoconversion in the highest baseline PDRP tertile (>1.47) compared with the middle (0.23–1.47) and lowest (≤0.23) tertiles (log-rank p=0.004).

Conclusion: In iRBD, increased PDRP expression is associated with a higher risk of phenoconversion. Both baseline and longitudinal PDRP measures predict conversion, supporting PDRP expression as a biomarker of disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-predictive-value-of-the-18f-fdg-pet-derived-parkinsons-disease-related-pattern-for-neurodegenerative-disease-progression-in-isolated-rem-sleep-behavior-disorder/