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Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis
  1. Zhihong Lyu1,2,
  2. Shuxin Zheng1,
  3. Xiaoyuan Zhang1,2,
  4. Yiling Mai1,
  5. Jiyang Pan3,
  6. Thomas Hummel4,
  7. Antje Hähner4,
  8. Laiquan Zou1,2
  1. 1 Chemical Senses and Mental Health Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
  2. 2 Department of Psychiatry, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
  3. 3 Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
  4. 4 Smell & Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Sachsen, Germany
  1. Correspondence to Laiquan Zou, Chemical Senses and Mental Health Laboratory, Department of Psychology, Southern Medical University, Guangzhou 510515, China; zoulq{at}; Xiaoyuan Zhang, Department of Psychology, School of Public Health, Southern Medical University, No.1023 Shatainan Road, Guangzhou 510515, Guangdong, China; zhxy{at}


Olfactory impairment and rapid eye movement sleep behaviour disorder (RBD) are prodromal symptoms of Parkinson’s disease (PD) that may be associated with each other. This review aims to investigate the significance of olfaction in the diagnosis and prognosis of patients with RBD and to assess moderating factors affecting olfactory performance. We searched articles on olfaction in RBD and PD in five electronic databases. We identified 32 studies for the systematic review and used 28 of those, including 2858 participants for meta-analysis. Results revealed significant deficits in odour identification (g=−1.80; 95% CI: −2.17 to −1.43), threshold (g=−1.29; 95% CI: −1.67 to −0.91), discrimination (g=−1.08; 95% CI: −1.28 to −0.87) and overall olfactory function (g=−1.64; 95% CI: −1.94 to −1.35) in patients with RBD. Except for the Unified Parkinson's Disease Rating Scale Part III scores, none of the known moderating variables (including age, sex, disease duration and years of education) accounted for the olfactory function heterogeneity in patients with RBD. We identified similar olfactory impairments in patients with RBD and patients with PD (either with or without underlying RBD). These findings suggest that olfactory impairment may be a sensitive and stable diagnostic biomarker of RBD and appears to be useful for identifying patients with idiopathic RBD at high risk for early conversion to PD.

  • sleep disorders
  • Parkinson's disease
  • meta-analysis

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  • ZL and SZ contributed equally.

  • Contributors ZL and LZ conceived the study. ZL and SZ selected reports and extracted the data. ZL, SZ and YM analysed and interpreted the data. ZL, XZ and LZ wrote the first draft of the manuscript. All authors critically revised the manuscript for intellectual content and approved the final version.

  • Funding This work was supported by the National Natural Science Foundation of China (grant number: 31 700 963), the Natural Science Foundation of Guangdong Province, China (grant number: 2019A1515012135), and the Medical Science and Technology Foundation of Guangdong Province, China (grant number A2019192)

  • Disclaimer These funding agents had no further role in any aspect of the study or the writing of this paper.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.