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Abstract
Background: It remains unclear how brain metabolic activities transform in response to dopamine deficiency in the prodromal and early phases of Parkinson's disease (PD).

Objective: To investigate the relationship between nigrostriatal dopaminergic denervation and brain glucose metabolism in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and early PD.

Methods: This cohort study included 28 patients with polysomnography-confirmed iRBD, 24 patients with de novo PD with probable rapid eye movement sleep behavior disorder (denovo PD), and 28 healthy controls (HCs) who underwent two positron emission tomography scans with 18 F-fluorodeoxyglucose (all participants) and 18 F-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (except for one denovo PD patient and 15 HCs). We analyzed striatal and voxel-wise whole-brain glucose metabolism in relation to nigrostriatal dopaminergic integrity and comparatively investigated the whole-brain metabolic connectivity among the groups. We also assessed longitudinal metabolic changes against progressive dopaminergic denervation over 4 years in the iRBD group.

Results: From HCs to iRBD and finally to the denovo PD, dopaminergic integrity positively correlated with metabolic activity in the caudate, whereas a negative correlation was observed in the posterior putamen. In the iRBD group, there was a metabolic increase in the inferior orbitofrontal cortex against putaminal dopaminergic denervation at baseline, but negative correlations were newly observed in the superior orbitofrontal cortex and superior frontal gyrus at the 4-year follow-up. The denovo PD group showed negative correlations in the cerebellum and fusiform gyrus. Intra- and inter-regional metabolic connectivities in the parieto-occipital cortices were enhanced in the iRBD group compared with the denovo PD and HC groups. In the iRBD group, overall metabolic connectivity was strengthened along with enhanced basal ganglia-frontal connection by advancing dopaminergic denervation.

Conclusions: Our findings suggest diverse trajectories of metabolic responses associated with dopaminergic denervation between individual brain areas in the prodromal and early PD stages. © 2022 International Parkinson and Movement Disorder Society.

Affiliations

Ryul Kim 1, Heejung Kim 2 3, Yu Kyeong Kim 3 4, Eun Jin Yoon 3 4, Hyun Woo Nam 5, Beomseok Jeon 6, Jee-Young Lee 5
1Department of Neurology, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea.
2Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
3Department of Nuclear Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, South Korea.
4Memory Network Medical Research Center, Seoul National University, Seoul, South Korea.
5Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.
6Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.