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July 21, 2020; 95 (3) Article

Patterns of striatal dopamine depletion in early Parkinson disease

Prognostic relevance

Seok Jong Chung, Hye Sun Lee, Han Soo Yoo, Yang Hyun Lee, Phil Hyu Lee, Young H. Sohn
First published July 2, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009878
Seok Jong Chung
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Hye Sun Lee
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Han Soo Yoo
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Yang Hyun Lee
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Phil Hyu Lee
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Young H. Sohn
From the Department of Neurology (S.J.C., H.S.Y., Y.H.L., P.H.L., Y.H.S.) and Biostatistics Collaboration Unit (H.S.L.), Yonsei University College of Medicine, Seoul, South Korea.
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Patterns of striatal dopamine depletion in early Parkinson disease
Prognostic relevance
Seok Jong Chung, Hye Sun Lee, Han Soo Yoo, Yang Hyun Lee, Phil Hyu Lee, Young H. Sohn
Neurology Jul 2020, 95 (3) e280-e290; DOI: 10.1212/WNL.0000000000009878

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Abstract

Objective To investigate whether the patterns of striatal dopamine depletion on dopamine transporter (DAT) scans could provide information on the long-term prognosis in Parkinson disease (PD).

Methods We enrolled 205 drug-naive patients with early-stage PD, who underwent 18F-FP-CIT PET scans at initial assessment and received PD medications for 3 or more years. After quantifying the DAT availability in each striatal subregion, factor analysis was conducted to simplify the identification of striatal dopamine depletion patterns and to yield 4 striatal subregion factors. We assessed the effect of these factors on the development of levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia during the follow-up period (6.84 ± 1.80 years).

Results The 4 factors indicated which striatal subregions were relatively preserved: factor 1 (caudate), factor 2 (more-affected sensorimotor striatum), factor 3 (less-affected sensorimotor striatum), and factor 4 (anterior putamen). Cox regression analyses using the composite scores of these striatal subregion factors as covariates demonstrated that selective dopamine depletion in the sensorimotor striatum was associated with a higher risk for developing LID. Selective dopamine loss in the putamen, particularly in the anterior putamen, was associated with early development of wearing-off. Selective involvement of the anterior putamen was associated with a higher risk for dementia conversion. However, the patterns of striatal dopamine depletion did not affect the risk of FOG.

Conclusions These findings suggested that the patterns of striatal dopaminergic denervation, which were estimated by the equation derived from the factor analysis, have a prognostic implication in patients with early-stage PD.

Glossary

ADL=
activities of daily living;
CI=
confidence interval;
DAT=
dopamine transporter;
18F-FP-CIT=
18F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane;
FOG=
freezing of gait;
HR=
hazard ratio;
K-MMSE=
Korean version of the Mini-Mental State Examination;
LED=
levodopa equivalent dose;
LID=
levodopa-induced dyskinesia;
PD=
Parkinson disease;
PDD=
Parkinson disease dementia;
UPDRS-III=
Unified Parkinson’s Disease Rating Scale Part III;
VOI=
volume of interest

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received September 17, 2019.
  • Accepted in final form December 27, 2019.
  • © 2020 American Academy of Neurology
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