Dataset Information

A New Metabolic Network Correlated with Olfactory and Executive Dysfunctions in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

ABSTRACT:

Background and purpose

To identify a metabolic network reflecting neurodegeneration in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).

Methods

We recruited a prospective cohort comprising patients with de novo Parkinson's disease (PD) with probable REM sleep behavior disorder (PDRBD, n=21), polysomnography-confirmed iRBD patients (n=28), and age-matched healthy controls (HC) (n=24). PDRBD-related spatial covariance pattern (PDRBD-RP) were determined from ¹?F-fluorodeoxyglucose PET images of the PDRBD group and validated by reproduction in a separate PD cohort with polysomnography-confirmed REM sleep behavior disorder (n=11). We also confirmed via ¹?F-N-3-fluoropropyl-2?-carboxymethoxy-3?-(4-iodophenyl)-nortropane PET that none of our iRBD patients had any loss of dopamine transporters (DATs) suggestive of PD. Differences in the PDRBD-RP across groups were compared, and the clinical significance of these metabolic patterns in iRBD patients was further evaluated based on relationships with olfactory and cognitive functions, and striatal DAT densities.

Results

The PDRBD-RP reflected the previously reported PD-related covariance pattern and additionally showed relative metabolic increases in the hippocampus and premotor cortex. The PDRBD-RP gradually increased from the HC to iRBD patients and to the de novo and validation PDRBD groups. In iRBD patients, the PDRBD-RP was negatively correlated with olfactory and frontal executive functions (age-controlled p<0.01 for both), and tended to be negatively correlated with the striatal DAT density, although this was insignificant after age adjustment. During the mean follow-up period of 3.5 years, 5 of 11 iRBD patients with PDRBD-RP elevation had developed Lewy body diseases, whereas those without PDRBD-RP elevation had not.

Conclusions

Our results suggest that PDRBD-RP is an effective biomarker for monitoring the progression to neurodegenerative disease in iRBD patients.

SUBMITTER: Yoon EJ

PROVIDER: S-EPMC6444138 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

A New Metabolic Network Correlated with Olfactory and Executive Dysfunctions in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Yoon Eun Jin EJ Lee Jee Young JY Nam Hyunwoo H Kim Han Joon HJ Jeon Beomseok B Jeong Jae Min JM Kim Yu Kyeong YK

Journal of clinical neurology (Seoul, Korea) 20190311 2

<h4>Background and purpose</h4>To identify a metabolic network reflecting neurodegeneration in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).<h4>Methods</h4>We recruited a prospective cohort comprising patients with <i>de novo</i> Parkinson's disease (PD) with probable REM sleep behavior disorder (PDRBD, <i>n</i>=21), polysomnography-confirmed iRBD patients (<i>n</i>=28), and age-matched healthy controls (HC) (<i>n</i>=24). PDRBD-related spatial covariance patt ...[more]

PMID: 30877691

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Project description:Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an ?-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and underlying mechanisms and represent potentially useful biomarkers for disease-associated molecular changes. To test this hypothesis, we assessed the serum glycome of patients with RBD and compared to that of healthy controls. NanoRPLC-MS was used to generate quantitative N-glycan profiles while high-temperature PGC-LC-MS platform was employed to generate quantitative isomeric N-glycan profiles. By analyzing permethylated glycans derived from human blood sera on C18-LC-MS/MS, we identified 59 N-glycan structures in healthy (control) cohort, 56 N-glycans in RBD cohort. Sixteen N-glycans structures were found to be significantly altered in the RBD cohort (p < 0.05). N-glycans with the composition of HexNAc4 Hex5 Fuc1 , HexNAc5 Hex5 , and HexNAc4 Hex5 Fuc1 NeuAc1 presented the most substantial difference between controls and RBD patients (p < 0.01). HexNAc4 Hex5 Fuc1 NeuAc1 showed a relatively high abundance (3.1 ± 0.7% in the control cohort versus 4 ± 3% in the idiopathic RBD cohort). These N-glycans can be potential diagnostic biomarker candidates and provide a window into underlying neurodegenerative processes in patients with idiopathic RBD. In addition, 7 N-glycan isomers were significantly different between controls and RBD patients (p < 0.05). HexNAc4 Hex5 Fuc1 NeuAc1 (4511-2) and HexNAc4 Hex5 Fuc1 NeuAc2 (4512-2) showed the most substantial difference between the control and idiopathic RBD cohorts (p < 0.001). Levels of both these two isomeric structures were higher in the idiopathic RBD cohort. Further larger studies are required to assess the reproducibility of these findings and to elucidate the role played by the changes in glycan structures in the pathogenetic mechanisms of RBD. This information will be instrumental in developing molecular therapeutic targets to promote neuroprotection and prevention of neurodegeneration.

Project description:Idiopathic rapid eye movement sleep behavior disorder (iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients (male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls (male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume (GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital (approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry (ISRCTN18238599).

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Dataset Information

A New Metabolic Network Correlated with Olfactory and Executive Dysfunctions in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Background and purpose

Methods

Results

Conclusions

Publications

A New Metabolic Network Correlated with Olfactory and Executive Dysfunctions in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Similar Datasets

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