Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease

Han Soo Yoo, Seok Jong Chung, Su Jin Chung, Hyojeong Moon, Jung Su Oh, Jae Seung Kim, Jin Yong Hong, Byoung Seok Ye, Young Ho Sohn, Phil Hyu Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. Methods: From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. Results: The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033). Conclusion: This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume45
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

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Dyskinesias
Levodopa
Parkinson Disease
Dopamine
Dopamine Plasma Membrane Transport Proteins
Putamen
Corpus Striatum
Denervation
Positron-Emission Tomography
Linear Models
Regression Analysis
Demography

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Yoo, Han Soo ; Chung, Seok Jong ; Chung, Su Jin ; Moon, Hyojeong ; Oh, Jung Su ; Kim, Jae Seung ; Hong, Jin Yong ; Ye, Byoung Seok ; Sohn, Young Ho ; Lee, Phil Hyu. / Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease. In: European Journal of Nuclear Medicine and Molecular Imaging. 2018 ; Vol. 45, No. 3. pp. 423-431.
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abstract = "Purpose: Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. Methods: From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. Results: The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033). Conclusion: This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.",
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Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease. / Yoo, Han Soo; Chung, Seok Jong; Chung, Su Jin; Moon, Hyojeong; Oh, Jung Su; Kim, Jae Seung; Hong, Jin Yong; Ye, Byoung Seok; Sohn, Young Ho; Lee, Phil Hyu.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 45, No. 3, 01.03.2018, p. 423-431.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease

AU - Yoo, Han Soo

AU - Chung, Seok Jong

AU - Chung, Su Jin

AU - Moon, Hyojeong

AU - Oh, Jung Su

AU - Kim, Jae Seung

AU - Hong, Jin Yong

AU - Ye, Byoung Seok

AU - Sohn, Young Ho

AU - Lee, Phil Hyu

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N2 - Purpose: Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. Methods: From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. Results: The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033). Conclusion: This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

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