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Abstract
Background: It remains unclear whether and how the isolated rapid eye movement (REM) sleep behavior disorder (iRBD)-related metabolic pattern (RBDRP) changes with disease progression in iRBD.

Objective: To examine longitudinal changes in RBDRP expression in iRBD patients and to explore trajectories of relative metabolic activities of individual brain regions constituting RBDRP.

Methods: In this cohort study, 25 iRBD patients (mean age [±standard deviation], 69.2 ± 5.3 years; 12 [48%] patients were men) and 24 age-matched healthy controls were included. The patients underwent at least two 18 F-fluorodeoxyglucose positron emission tomography scans at baseline and at the 2-year and/or 4-year follow-ups. We measured the RBDRP expression of the patients and controls which was validated by reproduction in a separate iRBD cohort (n = 13).

Results: At baseline, the RBDRP expression discriminated iRBD patients from healthy controls. However, the RBDRP expression z scores tended to decrease over time in the patients, especially with longer follow-ups, and this tendency was observed even in patients with high-risk of phenoconversion. Furthermore, the degree of RBDRP expression at baseline did not predict the disease conversion. The RBDRP breakdown was mainly provoked by the attenuation of relative hypermetabolism in the frontal cortex including premotor areas and relative hypometabolism in the occipital cortex. The putaminal metabolic activity increased steadily with the disease progression.

Conclusions: The RBDRP expression in iRBD patients was altered significantly over time. Some of the brain metabolic changes seem to represent attempted functional compensation against ongoing neurodegeneration. The RBDRP expression measurement at one time point may not be a reliable biomarker for predicting disease conversion. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

본 연구진은 F-18-fluorodeoxyglucose (FDG) PET 영상을 이용하여 Scaled Subprofile Model, Principal Component Analysis (SSM-PCA)에 기초하여 파킨슨병의 전구단계인 특발성렘수면행동장애 환자들의 뇌대사패턴을 설명할 수 있는 공간 공분산 패턴(spatial covariance pattern)을 만들어(그림 1) 2년 및 4년째 추적 영상을 촬영하여 이 공간 공분산 패턴이 어떻게 변화하는지 분석하였습니다.

본 논문은 최초의 전향적 분석을 통해 렘수면행동장애 환자에서 보이는 뇌대사능 공간 공분산 패턴이 시간이 지남에 따라 breaking down 되면서 점차 파킨슨병 환자 및 루이소체 치매의 공분산패턴으로 build-up 되어가는 것을 보여주었다는 점에서 의의가 있습니다 (그림 2). 특히 렘수면행동장애는 이미 알파시누클린병리가 시작된 전구파킨슨병 단계이므로 뇌대사능의 공간 공분산 패턴도 변화한다는 것을 보여줌으로써, 신경퇴행이 진행형이며, 뇌대사능도 이에 따라 변화하고 있다는 사실을 잘 보여주었습니다.

<그림 1> A. RBD-related pattern 의 발편이 정상대조군(control) 에 비해 idiopathic RBD (iRBD)에서 증가해 있음. B. RBD-related pattern을 구성하는 주요 뇌영역들

<그림 2> RBD-related pattern 이 2년 및 4년째 되면서 점차 감소하는 것을 보여주는 그래프. RBD-related pattern 과 PD-related pattern에서 반대로 기여하는 댚적인 영역인 premotor cortex, putamen, 그리고 lingual gyrus 의 뇌대사능이 각각 RBD-related pattern에서 PD-related pattern을 구성하는 방향으로 변화하는 모습을 보여주는 그래프.

Affiliations

Ryul Kim  1   2 , Jee-Young Lee  2 , Yu Kyeong Kim  3 , Heejung Kim  3   4 , Eun Jin Yoon  3 , Jung Hwan Shin  5 , Dallah Yoo  6 , Hyunwoo Nam  2 , Beomseok Jeon  5
1 Department of Neurology, Inha University Hospital, Incheon, South Korea.
2 Department of Neurology, Seoul National University-Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.
3 Department of Nuclear Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea.
4 Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
5 Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
6 Department of Neurology, Kyung Hee University Hospital, Seoul, South Korea.