Objective: To characterize the cerebral metabolic pattern of GBA-associated Parkinson’s disease (GBA-PD) using 18F-FDG PET/CT and to compare its longitudinal characteristic with genetically undefined Parkinson’s disease (GU-PD).

Background: GBA mutations are among the most important genetic determinants of Parkinson’s disease and are associated with more rapid disease progression. Although previous neuroimaging studies suggest distinct brain dysfunction in GBA-PD, its metabolic characteristics and longitudinal evolution remain unclear.

Method: 18F-FDG PET/CT was performed in 51 GBA-PD and 60 GU-PD patients between February 2012, and March 2024, including longitudinal follow-up in 16 GBA-PD and 23 GU-PD cases. We used standardized uptake value ratios (SUVR) analyzed brain glucose metabolism and linear mixed-effects models adjusted for sex, and disease duration.

Results: At baseline, GBA-PD patients showed bilateral hypermetabolism in limbic and subcortical structures, including the brainstem, amygdala, cerebellar cortex, putamen, and hippocampus, as well as in frontotemporal associative cortices such as the entorhinal cortex, insular cortex, rostral anterior cingulate cortex, orbitofrontal cortex, superior and middle temporal cortices, and temporal pole. In contrast, hypometabolism was mainly observed in posterior visual–parietal regions, including the lingual gyrus, lateral occipital cortex, pericalcarine cortex, superior and inferior parietal cortices, cuneus, precuneus, and caudal middle frontal cortex. Longitudinally, GBA-PD exhibited progressive metabolic increases in limbic and basal ganglia regions, including the entorhinal cortex, hippocampus, globus pallidus, amygdala, parahippocampal cortex, and putamen, with consistently higher SUVRs and faster progression than GU-PD. In contrast, GU-PD showed slower increases and declining trajectories in the entorhinal and parahippocampal cortices. These group differences remained significant after FDR correction (P < 0.05).

Conclusion: GBA-PD exhibited a disease-specific metabolic pattern characterized by limbic–frontotemporal and subcortical hypermetabolism with posterior cortical hypometabolism. Accelerated longitudinal increases in limbic–basal ganglia activity suggest selective network vulnerability that may underlie its aggressive clinical course and provide potential targets for biomarker development and neuromodulatory intervention.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/metabolic-brain-pattern-and-longitudinal-progression-in-gba-associated-parkinsons-disease-revealed-by-18f-fdg-pet-ct/