Correlations between dopaminergic dysfunction and abnormal metabolic network activity in REM sleep behavior disorder

Objectives: Striatal dopamine transporter (DAT) deficiency and abnormal expression of Parkinson’s disease (PD) related pattern (PDRP) have been observed in patients with idiopathic REM sleep behavior disorder (IRBD). But the relationship between the two distinct measures remains unclear. This study aimed to investigate the correlations between dopaminergic dysfunction and abnormal metabolic network activity in IRBD patients with comparison to PD using a dual tracer imaging design.

Methods: A total of 37 IRBD patients, 86 PD patients (mild, H&Y stage 1, 23 patients; moderate, H&Y2-3, 48 patients; advanced, H&Y4-5, 15 patients) and 15 control subjects matched in age underwent concurrent PET scans with ¹¹C-CFT to quantify dopaminergic dysfunction and ¹⁸F-FDG to quantify PDRP expression. To perform the investigations further on a hemispheric basis, some scans (both ¹¹C-CFT and ¹⁸F-FDG) were flipped so that all hemispheres more affected appeared on the right side of the brain. Differences in regional DAT binding and PDPR values among patient groups and normal controls were assessed by using one-way ANOVA with post hoc Bonferroni tests. The effect of the hemispheres and hemisphere × group interaction was evaluated by two-way ANOVA using a general linear model with repeated measures. Correlations between regional ¹¹C-CFT uptake, network expression and UPDRS motor ratings (PD only) were evaluated using Pearson correlation coefficients. All analyses were performed using SPSS software and considered significant at p < 0.05.

Results: IRBD patients were divided into two subgroups: those with relatively normal (IRBD-RN) or abnormal (IRBD-AB) striatal DAT binding. Significantly decreased striatal DAT binding and increased PDRP scores were present in all patient groups, except for IRBD-RN, relative to the controls. There was a significant effect of hemisphere and hemisphere × group interaction for striatal DAT binding but not for PDRP expression. Significant correlations were observed between DAT binding and PDRP expression in the IRBD-AB and PD groups but not in the IRBD-RN group. Conclusions: IRBD patients present with an intermediate state in striatal DAT distribution and PDRP activity between PD and normal controls. The modest correlations between the two measures in both IRBD and PD suggest differences in network activity that cannot be fully explained by nigrostriatal dopaminergic denervation.