Brain Metabolic Correlates of Dopaminergic Denervation in Prodromal and Early Parkinson's Disease

Ryul Kim; Heejung Kim; Yu Kyeong Kim; Eun Jin Yoon; Hyun Woo Nam; Beomseok Jeon; Jee-Young Lee

doi:10.1002/mds.29177

Brain Metabolic Correlates of Dopaminergic Denervation in Prodromal and Early Parkinson's Disease

Mov Disord. 2022 Oct;37(10):2099-2109. doi: 10.1002/mds.29177. Epub 2022 Aug 12.

Authors

Ryul Kim¹, Heejung Kim^{2

3}, Yu Kyeong Kim^{3

4}, Eun Jin Yoon^{3

4}, Hyun Woo Nam⁵, Beomseok Jeon⁶, Jee-Young Lee⁵

Affiliations

¹ Department of Neurology, Inha University Hospital, Inha University College of Medicine, Incheon, South Korea.
² Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
³ Department of Nuclear Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, South Korea.
⁴ Memory Network Medical Research Center, Seoul National University, Seoul, South Korea.
⁵ Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.
⁶ Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.

PMID: 36250497
DOI: 10.1002/mds.29177

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.

Keywords: Parkinson's disease; REM sleep behavior disorder; connectivity; dopamine; metabolic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Brain / metabolism
Cohort Studies
Denervation
Dopamine / metabolism
Glucose
Humans
Nortropanes*
Parkinson Disease* / complications
REM Sleep Behavior Disorder* / complications

Substances

Nortropanes
Glucose
Dopamine