Dataset Information

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder.

ABSTRACT:

Objective

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson's disease (PD). Positron emission tomography (PET) with ¹⁸F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study.

Methods

19 iRBD patients, 38 PD patients and 19 HC subjects underwent ¹⁸F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between ¹⁸F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between ¹⁸F-FDG uptake and the Unified Parkinson's Disease Rating Scale motor (UPDRS III) scores in the PD group.

Results

PD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative ¹⁸F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores.

Conclusion

Cerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

SUBMITTER: Han X

PROVIDER: S-EPMC7322340 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder.

Han Xianhua X Wu Ping P Alberts Ian I Zhou Hucheng H Yu Huan H Bargiotas Panagiotis P Yakushev Igor I Wang Jian J Höglinger Guenter G Förster Stefan S Bassetti Claudio C Oertel Wolfgang W Schwaiger Markus M Huang Sung-Cheng SC Cumming Paul P Rominger Axel A Jiang Jiehui J Zuo Chuantao C Shi Kuangyu K

NeuroImage. Clinical 20200526

<h4>Objective</h4>Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson's disease (PD). Positron emission tomography (PET) with <sup>18</sup>F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a contin ...[more]

PMID: 32570206

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Project description:ObjectiveTo precisely delineate clinical risk factors for conversion from idiopathic REM sleep behavior disorder (RBD) to Parkinson disease, dementia with Lewy bodies, and multiple system atrophy, in order to enable practical planning and stratification of neuroprotective trials against neurodegenerative synucleinopathy.MethodsIn a 10-year prospective cohort, we tested prodromal Parkinson disease markers in 89 patients with idiopathic RBD. With Kaplan-Meier analysis, we calculated risk of neurodegenerative synucleinopathy, and using Cox proportional hazards, tested the ability of prodromal markers to identify patients at higher disease risk. By combining predictive markers, we then designed stratification strategies to optimally select patients for definitive neuroprotective trials.ResultsThe risk of defined neurodegenerative synucleinopathy was high: 30% developed disease at 3 years, rising to 66% at 7.5 years. Advanced age (hazard ratio [HR] = 1.07), olfactory loss (HR = 2.8), abnormal color vision (HR = 3.1), subtle motor dysfunction (HR = 3.9), and nonuse of antidepressants (HR = 3.5) identified higher risk of disease conversion. However, mild cognitive impairment (HR = 1.8), depression (HR = 0.63), Parkinson personality, treatment with clonazepam (HR = 1.3) or melatonin (HR = 0.55), autonomic markers, and sex (HR = 1.37) did not clearly predict clinical neurodegeneration. Stratification with prodromal markers increased risk of neurodegenerative disease conversion by 200%, and combining markers allowed sample size reduction in neuroprotective trials by >40%. With a moderately effective agent (HR = 0.5), trials with fewer than 80 subjects per group can demonstrate definitive reductions in neurodegenerative disease.ConclusionsUsing stratification with simply assessed markers, it is now not only possible, but practical to include patients with RBD in neuroprotective trials against Parkinson disease, multiple system atrophy, and dementia with Lewy bodies.

Dataset Information

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder.

Objective

Methods

Results

Conclusion

Publications

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder.

Similar Datasets

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