[18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) Characterizes Neurodegeneration Levels Across the α-Synucleinopathy Continuum.
This study demonstrates that [18F]FDG PET disease-related metabolic patterns and regional analyses can distinguish prodromal iRBD, converters, PD, and DLB and track progressive neurodegeneration across the α‑synucleinopathy continuum, with strongest performance in cognitive‑predominant…
What the AI sees
This study demonstrates that [18F]FDG PET disease-related metabolic patterns and regional analyses can distinguish prodromal iRBD, converters, PD, and DLB and track progressive neurodegeneration across the α‑synucleinopathy continuum, with strongest performance in cognitive‑predominant…
Research significance
Offers a clinically translatable biomarker for patient stratification, progression monitoring, and trial endpoints—particularly for dementia‑first synucleinopathies—enabling better selection of participants and mechanism‑linked outcome measures in therapeutic development.
Source abstract
BACKGROUND: [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) represents an endorsed neurodegeneration biomarker in neuronal α-synucleinopathies. Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents a prodromal stage of such disorders. OBJECTIVES: To assess [18F]FDG PET as a neurodegeneration biomarker, using published brain metabolic disease-related patterns, and a regional-based approach, across the prodromal to overt α-synucleinopathy continuum. METHODS: We included 83 prodromal subjects with iRBD, comprising non-converters (n = 56) and converters (n = 27) to an overt α-synucleinopathy (either Parkinson's disease [PD] or dementia with Lewy bodies [DLB]) according to the last available follow-up, and 85 subjects with PD (n = 40) and DLB (n = 45). For comparison, we enrolled a group of healthy subjects (n = 41). Participants underwent brain [18F]FDG PET at baseline. Analysis of covariance was used to test the ability of previously published [18F]FDG PET disease-related patterns in characterizing neurodegeneration levels along the prodromal to overt α-synucleinopathy continuum, and across the motor-predominant (parkinsonism-first) and the cognitive-predominant (dementia-first) clinical trajectories. We further assessed metabolic changes using a regional-based approach. RESULTS: All disease-related patterns effectively discriminated clinical stages, from prodromal to overt α-synucleinopathies, with comparable performance. [18F]FDG PET significantly distinguished all groups along the cognitive-predominant pathway; whereas in the motor-predominant pathway, converter patients were not significantly discriminated from non-converters. Regionally, the inferior parietal, precuneus, and middle frontal areas exhibited the most prominent decrease in [18F]FDG uptake with progression, alongside relative parallel progressive increases in the cerebellum, pons, parahippocampal areas, putamen, and pallidum. CONCLUSIONS: [18F]FDG PET disease-related patterns efficiently characterize neurodegeneration from prodromal to overt α-synucleinopathy, best assessing the cognitive-predominant (dementia-first) pathway. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.