The Metabolic Pattern of Idiopathic REM Sleep Behavior Disorder Reflects Early-Stage Parkinson Disease

TY - JOUR

T1 - The Metabolic Pattern of Idiopathic REM Sleep Behavior Disorder Reflects Early-Stage Parkinson Disease

AU - REMPET Study Group

AU - Meles, Sanne K.

AU - Renken, Remco J.

AU - Janzen, Annette

AU - Vadasz, David

AU - Pagani, Marco

AU - Arnaldi, Dario

AU - Morbelli, Silvia

AU - Nobili, Flavio

AU - Mayer, Geert

AU - Leenders, Klaus L.

AU - Oertel, Wolfgang H.

AU - Sittig-Wiegand, Elisabeth

AU - Depboylu, Candan

AU - Reetz, Kathrin

AU - Overeem, Sebastiaan

AU - Pijpers, Angelique

AU - Reesink, Fransje E.

AU - Van Laar, Teus

AU - Teune, Laura K.

AU - Höffken, Helmut

AU - Luster, Marcus

AU - Timmermann, Lars

AU - Kesper, Karl

AU - Adriaanse, Sofie M.

AU - Booij, Jan

AU - Sambuceti, Gianmario

AU - Girtler, Nicola

AU - Jonsson, Cathrine

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson disease (PD) and other Lewy body disorders. Spatial covariance analysis of 18F-FDG PET data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it with the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we studied the expression of the iRBD pattern in de novo PD patients. Methods: The iRBD-related pattern was identified in 18F-FDG PET scans of 21 patients with polysomnographically confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in 18F-FDG PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable REM sleep behavior disorder (RBD) according to the Mayo Sleep Questionnaire. Neuropsychologic evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom 16 also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms. Results: The iRBD-related pattern was characterized by relative hypermetabolism in the cerebellum, brain stem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in the middle cingulate, temporal, occipital, and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBDrelated pattern was significantly expressed in PD patients compared with controls (P < 0.0001). iRBD-related pattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern (iRBDRP) expression was higher in PD-MCI patients than in PD patients with preserved cognition (P = 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP (r = 0.94, P < 0.0001). Conclusion: Our results show that the iRBDRP is an early manifestation of the PDRP. Expression of both PDRP and iRBDRP was higher in patients with a more severe form of PD (PD-MCI), which indicates that expression of the 2 patterns increases with disease severity.

AB - Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson disease (PD) and other Lewy body disorders. Spatial covariance analysis of 18F-FDG PET data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it with the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we studied the expression of the iRBD pattern in de novo PD patients. Methods: The iRBD-related pattern was identified in 18F-FDG PET scans of 21 patients with polysomnographically confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in 18F-FDG PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable REM sleep behavior disorder (RBD) according to the Mayo Sleep Questionnaire. Neuropsychologic evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom 16 also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms. Results: The iRBD-related pattern was characterized by relative hypermetabolism in the cerebellum, brain stem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in the middle cingulate, temporal, occipital, and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBDrelated pattern was significantly expressed in PD patients compared with controls (P < 0.0001). iRBD-related pattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern (iRBDRP) expression was higher in PD-MCI patients than in PD patients with preserved cognition (P = 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP (r = 0.94, P < 0.0001). Conclusion: Our results show that the iRBDRP is an early manifestation of the PDRP. Expression of both PDRP and iRBDRP was higher in patients with a more severe form of PD (PD-MCI), which indicates that expression of the 2 patterns increases with disease severity.

KW - F-FDG-PET

KW - A-synucleinopathy

KW - Analysis

KW - Idiopathic REM

KW - Metabolic pattern

KW - Neurology

KW - Parkinson's disease related pattern

KW - PET/CT

KW - Sleep behavior disorder

KW - Statistical

UR - http://www.scopus.com/inward/record.url?scp=85048414340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048414340&partnerID=8YFLogxK

U2 - 10.2967/jnumed.117.202242

DO - 10.2967/jnumed.117.202242

M3 - Article

AN - SCOPUS:85048414340

VL - 59

SP - 1437

EP - 1444

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 9

ER -