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Non-motor Symptoms in Parkinson’s Disease Patients with Parkin Mutations: More Depression and Less Executive Dysfunction

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Abstract

The purpose of this study was to identify differences between genetically undefined (GU) early-onset Parkinson’s disease (EOPD) patients and carriers of Parkin mutations on non-motor symptoms (NMSs). EOPD patients (N = 261) underwent targeted sequencing of Parkinson’s disease (PD) related genes. Among them, 53 cases carried homozygous or compound heterozygous Parkin mutations (Parkin group) while 208 did not carry known causative PD mutations or risk factors of GBA or Parkin heterozygous mutations (GU group). NMSs were evaluated by face-to-face interviews, self-completed questionnaires and results on a neuropsychological battery. Linear regression and logistic regression models were applied to assess the predictors of NMSs. Parkin patients had younger ages of onset (AOO) (p < 0.001), longer disease durations (p < 0.001) and lower grades of Hoehn and Yarh (H&Y) (p = 0.007). Results on the neuropsychological battery showed a shorter time in Trail Making Test (TMT) (part B) in Parkin patients (p = 0.034) compared to GU patients. After adjusting for AOO, disease duration, H&Y, and levodopa equivalent daily dose (LEDD), there was a higher depression index on the Beck Depression Inventory (BDI) (p = 0.013) and better performance (p = 0.038) on executive function in the Parkin group compared to the GU group. No significant differences were found for autonomic functions, sleep-wake problems or other domains of cognitive function. Our study showed that the Parkin mutation status might be a good predictor of symptoms of depression without an impact on executive function. While these findings need to be confirmed in larger cohorts, they identify a need to screen for depression.

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Acknowledgements

This work was supported by grants from the Ministry of Science and Technology of China (2016YFC1306500), the National Natural Science Foundation of China (81571232, 81771372, 81701250, 81401048), the China Postdoctoral Science Foundation (2017 M610227), the Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZHANGJIANG LAB, the Science and Technology Commission of Shanghai Municipality (15ZR1435800) and a project from the Traditional Chinese Medical Fund (JA2015-Z002). We are especially grateful to Dr. James Koprich from Toronto Western Hospital and Dr. Long Chen from the NICU of Huashan Hospital for their kind help in the language editing.

Author information

Jie Song was responsible for analysis of the data and drafting the manuscript. Bo Shen was responsible for collection and analysis of the data. Yu-Jie Yang, Feng-Tao Liu, Jue Zhao, Yi-Lin Tang and Chen Chen were responsible for clinical care of the patients, data collection, performing the neuropsychological assessments and organizing the data. Zheng-Tong Ding and Jian-Jun Wu were responsible for taking care of the patients and interpreting the data. Yu An was responsible for interpreting the clinical data and genetic results of the patients. Jian Wang and Yi-Min Sun were responsible for the conception of the work, manuscript revision, taking care of the patients, supervision and final approval.

Correspondence to Yi-Min Sun or Jian Wang.

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Conflict of Interest

Jie Song, Bo Shen, Jue Zhao, Yu-Jie Yang, Yi-Lin Tang, Chen Chen, Zheng-Tong Ding, and Yu An report no disclosures relevant to the manuscript. Jian Wang was in charge of the projects 2016YFC1306500 from the Ministry of Science and Technology of China, National Natural Science Foundation of China (Nos. 81771372, 81571232), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and the ZHANGJIANG LAB. Jian-Jun Wu was in charge of a project from the Science and Technology Commission of Shanghai Municipality (15ZR1435800) and a project from the Traditional Chinese Medical Fund (JA2015-Z002). Yi-Min Sun was in charge of a project from the National Natural Science Foundation of China (No.81401048). Feng-Tao Liu was in charge of the National Natural Science Foundation of China project (No.81701250). Yu-Jie Yang was in charge of the China Postdoctoral Science Foundation project (2017 M610227).

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Song, J., Shen, B., Yang, Y. et al. Non-motor Symptoms in Parkinson’s Disease Patients with Parkin Mutations: More Depression and Less Executive Dysfunction. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-019-01444-3

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Keywords

  • Depression
  • Executive function
  • Non-motor symptoms
  • Parkin
  • Parkinson’s disease