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-naïve 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 (β = − 1.605, p < 0.001) and PC2 (β = 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 (β = − 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.
|Number of pages||10|
|Journal||Journal of Neural Transmission|
|Publication status||Published - 2023 Jan|
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A1A01059678) and a new faculty research seed money grant of Yonsei University College of Medicine for 2022 (2022–32-0059). Also, this research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI22C0224).
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry