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Dopaminergic damage pattern predicts phenoconversion time in isolated rapid eye movement sleep behavior disorder

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Abstract

Purpose

The exact phenoconversion time from isolated rapid eye movement (REM) sleep behavior disorder (iRBD) to synucleinopathies remains unpredictable. This study investigated whole-brain dopaminergic damage pattern (DDP) with disease progression and predicted phenoconversion time in individual patients.

Methods

Age-matched 33 iRBD patients and 20 healthy controls with 11C-CFT-PET scans were enrolled. The patients were followed up 2–10 (6.7 ± 2.0) years. The phenoconversion year was defined as the base year, and every 2 years before conversion was defined as a stage. Support vector machine with leave-one-out cross-validation strategy was used to perform prediction.

Results

Dopaminergic degeneration of iRBD was found to occur about 6 years before conversion and then abnormal brain regions gradually expanded. Using DDP, area under curve (AUC) was 0.879 (90% sensitivity and 88.3% specificity) for predicting conversion in 0–2 years, 0.807 (72.7% sensitivity and 83.3% specificity) in 2–4 years, 0.940 (100% sensitivity and 84.6% specificity) in 4–6 years, and 0.879 (100% sensitivity and 80.7% specificity) over 6 years. In individual patients, predicted stages correlated with whole-brain dopaminergic levels (r =  − 0.740, p < 0.001).

Conclusion

Our findings suggest that DDP could accurately predict phenoconversion time of individual iRBD patients, which may help to screen patients for early intervention.

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Data availability

The data that support the findings of this study are available upon reasonable request.

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Funding

This work was financially supported by the National Natural Science Foundation of China (81401135, 12175268, 12205329, 11975249, 81902282, 81771483, 81361120393), Medical Innovation Research Project of Shanghai Science and Technology Commission (21Y11903300), and Youth Medical Talents-Medical Imaging Practitioner Program by Shanghai Municipal Health Commission and Shanghai Medical and Health Development Foundation (SHWRS(2020)_087).

Author information

Author notes

  1. Shuang Feng and Jingjie Ge contributed equally to this work

Authors and Affiliations

  1. Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China

    Shuang Feng, Tianhao Zhang, Shilun Zhao, Baoci Shan & Binbin Nie

  2. School of Physics, Zhengzhou University, Zhengzhou, China

    Shuang Feng & Shujun Zhao

  3. Department of Nuclear Medicine/PET Centre, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

    Jingjie Ge, Qian Xu, Huamei Lin, Xiuming Li, Yihui Guan, Chuantao Zuo & Ping Wu

  4. National Center for Neurological Disorders & National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Jing’an District, Shanghai, China

    Jingjie Ge, Qian Xu, Huamei Lin, Xiuming Li, Jianjun Wu, Yihui Guan, Chuantao Zuo, Ping Wu & Huan Yu

  5. Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

    Jianjun Wu & Huan Yu

  6. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan District, Beijing, China

    Tianhao Zhang, Shilun Zhao, Baoci Shan & Binbin Nie

  7. Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Kuangyu Shi

  8. Computer Aided Medical Procedures, School of Computation, Information and Technology, Technical University of Munich, Munich, Germany

    Kuangyu Shi

Authors
  1. Shuang Feng
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  2. Jingjie Ge
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Contributions

B.N and P.W led the project. B.S and H.Y were responsible for the study concept and the design of the study. S.F carried out the neuroimaging data preprocessing and statistical analysis. J.G and Q.X were involved in sample analyses and data interpretation. S.F and J.G wrote the manuscript. Q.X, S.Z, C.Z, B.S, H.Y, B.N, and P.W made substantial contributions to the manuscript and provided critical comments. H.L, J.W, Y.G, T.Z, and S.Z participated in the discussions of the results and the manuscript. All authors had access to the data generated during the study, including the statistical analysis, and agreed with the decision to submit the article for publication.

Corresponding authors

Correspondence to Baoci Shan, Ping Wu, Binbin Nie or Huan Yu.

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The institutional review board of Huashan Hospital affiliated with Fudan University approved the study (No. KY2013-336).

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Informed consent was obtained from all participants or their assigned surrogate decision-makers.

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The authors declare no competing interests.

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Feng, S., Ge, J., Zhao, S. et al. Dopaminergic damage pattern predicts phenoconversion time in isolated rapid eye movement sleep behavior disorder. Eur J Nucl Med Mol Imaging 51, 159–167 (2023). https://doi.org/10.1007/s00259-023-06402-1

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