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Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease

Shi, Xinchong MM*; Zhang, Yan DSc; Xu, Shaohua MM; Kung, Hank F. DSc§; Qiao, Hongwen DSc; Jiang, LuLu MM; Zhu, Lin DSc; Guo, Qiyi MM; Yi, Chang ME*; Luo, Ganhua ME*; Wu, Lei MD; Pei, Zhong MD; Wang, Jian MD; Zhang, Xiangsong MD*; Chen, Ling MD

doi: 10.1097/RLU.0000000000002664
Original Articles
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Objective Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD.

Methods Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using 18F-DTBZ (18F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis.

Results Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus (P < 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs (P < 0.05).

Conclusion The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.

From the *Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong

Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Beijing

Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong

§Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA

Department of Nuclear Medicine, Xuanwu Hospital Capital Medical University, Beijing

Department of Neurology & National Clinical Research Center for Aging and Medicine, Huashan Hospital of Fudan University, Shanghai, China.

Received for publication February 25, 2019; revision accepted April 27, 2019.

Xinchong Shi and Yan Zhang contributed equally to this research and were responsible for initial writing.

Conflicts of interest and sources of funding: This work was supported by Guangdong Provincial Scientific Key R&D Program (2018B030337001), National Key R&D Program of China from Ministry of Science and Technology of China (2016YFC1306500, 2016YFC1306504 and 2016YFC1306304), Guangdong Science and Technology Foundation (2014A030304019), Guangdong Provincial Natural Science Foundation (2015A030313164), The Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003), Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases (2017B030314103), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment (201604020010), Beijing Science and Technology Project (Z151100003915116), and Novel Key-point Technological Project of Guangzhou (2018-1202-SF-0019). None declared to all authors.

Authors' roles: Research project: Ling Chen, Xiangsong Zhang and Hank F. Kung designed and organized this study. Lin Zhu, Zhong Pei and Jian Wang reviewed the study design and gave valuable suggestions. Research execution and statistical analysis: Shaohua Xu, Lulu Jiang, Qiyi Guo, and Lei Wu selected the patients with PD and assessed their motor and nonmotor symptoms. Yan Zhang, Hongwen Qiao, and Lin Zhu prepared the radiotracer 13F-AV133. Xinchongshi, Chang Yi, and Ganhua Luo were responsible for PET/CT imaging and data analysis. Manuscript writing: Xinchong Shi and Yan Zhang completed the initial writing, and Ling Chen and Hank F. Kung reviewed and revised the manuscript.

Correspondence to: Ling Chen, MD, Department of Neurology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. E-mail: chenl2@mail.sysu.edu.cn; Xiangsong Zhang, Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. E-mail: sd_zh@163.net.

Online date: June 14, 2019

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