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

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.

Automated summary

The study investigated whether different patterns of striatal dopamine depletion are associated with motor deficits in Parkinson's disease. A total of 404 drug-naive patients with early-stage PD were enrolled and underwent dopamine transporter imaging. Principal component analysis identified three patterns of dopamine depletion: overall deficiency, selective loss in the sensorimotor striatum, and symmetric loss in the striatum. Linear regression analysis revealed that overall deficiency and selective loss were associated with motor deficits, while symmetric loss was not. Mediation analysis showed that dopamine deficiency in the posterior putamen mediated the association between dopamine depletion patterns and motor deficits. These findings suggest that dopamine deficiency in the posterior putamen plays a crucial role in motor deficits in PD.