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White Matter Hyperintensities, Dopamine Loss, and Motor Deficits in De Novo Parkinson's Disease

 Seong Ho Jeong  ;  Hye Sun Lee  ;  Jin Ho Jung  ;  Kyoungwon Baik  ;  Yang Hyun Lee  ;  Han Soo Yoo  ;  Young H Sohn  ;  Seok Jong Chung  ;  Phil Hyu Lee 
 MOVEMENT DISORDERS, Vol.36(6) : 1411-1419, 2021-06 
Journal Title
Issue Date
Corpus Striatum / metabolism ; Cross-Sectional Studies ; Dopamine ; Dopamine Plasma Membrane Transport Proteins / metabolism ; Humans ; Parkinson Disease* / diagnostic imaging ; White Matter* / diagnostic imaging
Parkinson's disease ; axial motor symptoms ; dopamine transporter ; mediation analysis ; white matter hyperintensities
Background: White matter hyperintensities, prevalent in patients with Parkinson's disease (PD), significantly affect parkinsonian motor symptoms. The objective of this study was to investigate the relationship between white matter hyperintensities and nigrostriatal dopamine depletion and their interaction or mediating effects on motor symptoms in patients with drug-naive early-stage PD.

Methods: This cross-sectional study enrolled 501 patients with de novo PD who initially underwent [18 F] N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography and brain magnetic resonance imaging scans between April 2009 and September 2015 in a tertiary-care university hospital. We quantified dopamine transporter availability in each striatal subregion and assessed the severity of periventricular and lobar white matter hyperintensities using the Scheltens scale. The relationship between white matter hyperintensities, dopamine transporter availability in the posterior putamen, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was assessed using multivariate linear regression and mediation analyses.

Results: Periventricular and frontal white matter hyperintensities were generally associated with dopamine transporter availability in striatal subregions after adjusting for age at symptom onset, sex, disease duration, and vascular risk factors. There was an interaction effect between periventricular white matter hyperintensities and dopamine transporter availability in the posterior putamen for the axial motor score. The effect of white matter hyperintensities on UPDRS total score and bradykinesia subscore was indirectly mediated by dopamine transporter availability in the posterior putamen, whereas the axial sub-score was directly affected by white matter hyperintensities.

Conclusions: This study suggests that the detrimental effect of white matter hyperintensities on parkinsonian motor symptoms is more relevant and independent for axial motor impairments in the status of mildly decreased striatal dopamine transporter availability. © 2021 International Parkinson and Movement Disorder Society.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Baik, Kyoungwon(백경원) ORCID logo https://orcid.org/0000-0001-7215-375X
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Yang Hyun(이양현)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
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