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Patterns of striatal dopamine depletion and motor deficits in de novo Parkinson's disease

 Seong Ho Jeong  ;  Chan Wook Park  ;  Hye Sun Lee  ;  Yun Joong Kim  ;  Mijin Yun  ;  Phil Hyu Lee  ;  Young H Sohn  ;  Seok Jong Chung 
 JOURNAL OF NEURAL TRANSMISSION, Vol.130(1) : 19-28, 2023-01 
Journal Title
Issue Date
Corpus Striatum / diagnostic imaging ; Corpus Striatum / metabolism ; Dopamine ; Dopamine Plasma Membrane Transport Proteins / metabolism ; Humans ; Parkinson Disease* / complications ; Parkinson Disease* / diagnostic imaging ; Positron-Emission Tomography ; Putamen / diagnostic imaging ; Putamen / metabolism
Dopamine depletion ; Dopamine transporter ; Motor deficits ; Parkinson’s disease ; Principal component analysis
The background of this study is to investigate whether striatal dopamine depletion patterns (selective involvement in the sensorimotor striatum or asymmetry) are associated with motor deficits in Parkinson's disease (PD). We enrolled 404 drug-naive patients with early stage PD who underwent dopamine transporter (DAT) imaging. After quantifying DAT availability in each striatal sub-region, principal component (PC) analysis was conducted to yield PCs representing the spatial patterns of striatal dopamine depletion. Subsequently, multivariate linear regression analysis was conducted to investigate the relationship between striatal dopamine depletion patterns and motor deficits assessed using the Unified PD Rating Scale Part III (UPDRS-III). Mediation analyses were used to evaluate whether dopamine deficiency in the posterior putamen mediated the association between striatal dopamine depletion patterns and parkinsonian motor deficits. Three PCs indicated patterns of striatal dopamine depletion: PC1 (overall striatal dopamine deficiency), PC2 (selective dopamine loss in the sensorimotor striatum), and PC3 (symmetric dopamine loss in the striatum). Multivariate linear regression analysis revealed that PC1 (beta = - 1.605, p < 0.001) and PC2 (beta = 3.201, p < 0.001) were associated with motor deficits (i.e., higher UPDRS-III scores in subjects with severe dopamine depletion throughout the whole striatum or more selective dopamine loss in the sensorimotor striatum), whereas PC3 was not (beta = - 0.016, p = 0.992). Mediation analyses demonstrated that the effects of PC1 and PC2 on UPDRS-III scores were indirectly mediated by DAT availability in the posterior putamen, with a non-significant direct effect. Dopamine deficiency in the posterior putamen was most relevant to the severity of motor deficits in patients with PD, while the spatial patterns of striatal dopamine depletion were not a key determinant.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Yun Joong(김윤중) ORCID logo https://orcid.org/0000-0002-2956-1552
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Yun, Mijin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
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