Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease

Abstract Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potential...

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Main Authors: Zhengjie Yang, Yijie Xie, Kaixin Dou, Liying Yang, Anmu Xie
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.13508
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author Zhengjie Yang
Yijie Xie
Kaixin Dou
Liying Yang
Anmu Xie
author_facet Zhengjie Yang
Yijie Xie
Kaixin Dou
Liying Yang
Anmu Xie
author_sort Zhengjie Yang
collection DOAJ
description Abstract Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross‐sectional studies indicated certain motor and non‐motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed‐effect models were respectively conducted to investigate the cross‐sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross‐sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]‐adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR‐adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR‐adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid‐eye‐movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR‐adjusted p = 0.0120). Furthermore, changes in MDS‐UPDRS scores and the State–Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non‐motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.
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spelling doaj.art-586912a9df2b4cc0a0b7836c41ab4d872023-06-14T06:03:57ZengWileyClinical and Translational Science1752-80541752-80622023-06-011661021103810.1111/cts.13508Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's diseaseZhengjie Yang0Yijie Xie1Kaixin Dou2Liying Yang3Anmu Xie4Department of Neurology Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Clinical Laboratory Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Neurology Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Neurology Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Neurology Affiliated Hospital of Qingdao University Qingdao ChinaAbstract Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross‐sectional studies indicated certain motor and non‐motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed‐effect models were respectively conducted to investigate the cross‐sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross‐sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]‐adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR‐adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR‐adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid‐eye‐movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR‐adjusted p = 0.0120). Furthermore, changes in MDS‐UPDRS scores and the State–Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non‐motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.https://doi.org/10.1111/cts.13508
spellingShingle Zhengjie Yang
Yijie Xie
Kaixin Dou
Liying Yang
Anmu Xie
Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
Clinical and Translational Science
title Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
title_full Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
title_fullStr Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
title_full_unstemmed Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
title_short Associations of striatal dopamine transporter binding with motor and non‐motor symptoms in early Parkinson's disease
title_sort associations of striatal dopamine transporter binding with motor and non motor symptoms in early parkinson s disease
url https://doi.org/10.1111/cts.13508
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