Objective: To elucidate the pathological progression from rapid eye movement sleep behavior disorder (RBD) to Parkinson’s disease (PD), we investigated tissue-level neurodegenerative changes using multimodal imaging, including neuromelanin-sensitive MRI (NM), quantitative susceptibility mapping (QSM), and nuclear medicine imaging.

Background: RBD is considered a prodromal stage of α-synucleinopathy; however, the sequential pathological changes underlying progression to PD and the potential heterogeneity of disease pathways remain incompletely understood.

Method: Forty-two patients with PD, 13 patients with RBD, and 16 healthy controls (HC) underwent 3T-MRI. NM signal intensity and QSM values were quantified in the substantia nigra (SN) and locus coeruleus (LC) and compared among the three groups. In addition, patients with PD were stratified according to cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake into PD with reduced uptake (PD^MIBG+) and PD with preserved uptake (PD^MIBG−), and imaging measures were compared between these subgroups. Furthermore, the correlation between dopamine transporter (DAT) specific binding ratio (SBR) and SN-QSM values was analyzed in patients with PD and RBD.

Results: NM values of the SN were significantly lower in both the PD and RBD groups compared with HC (p < 0.01). In contrast, SN-QSM values were significantly higher only in the PD group (p < 0.05). NM values of the LC in the RBD and PD^MIBG+ groups were comparable and lower than those in the PD^MIBG− group, whereas SN imaging measures did not differ between PD^MIBG+ and PD^MIBG−. Furthermore, a significant inverse correlation was observed between DAT-SBR and SN-QSM values across patients with RBD and PD (r = −0.28, p < 0.01).

Conclusion: Our findings suggest a stepwise pathological process in which neuromelanin loss in the SN may precede significant iron deposition, which becomes evident at the clinical stage of PD. Distinct patterns of LC degeneration according to cardiac sympathetic denervation suggest heterogeneity in disease progression pathways. In addition, the association between DAT-SBR and SN-QSM values is compatible with the dying-back hypothesis in the nigrostriatal system.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenoconversion-from-rapid-eye-movement-sleep-behavior-disorder-to-parkinsons-disease-a-multimodal-imaging-study/