Association of Cardinal Motor Symptoms with Region-Specific Dopamine Transporter Activity in Mild to Moderate Parkinson's Disease

Introduction

PD is a clinical syndrome consisting of variable combinations of motor features of tremor, rigidity, postural instability, and akinesia–bradykinesia 1. The pathological hallmark of PD is loss of dopaminergic neurons in the substantia nigra pars compacta and the ventral tegmental area with somewhat asymmetric degeneration of their striatal terminals. At presentation, there are typically unilateral motor features that often later progress to bilateral motor features 2–4.

Abstract

Objective

To investigate the relationship between measures of the cardinal motor features and the degree of nigrostriatal dopaminergic denervation in patients with mild to moderate Parkinson's disease (PD).

Methods

PD patients (Hoehn and Yahr stages I–III, n=27) underwent C-β-CFT dopamine transporter (DAT) positron emission tomography. Clinical examination included the Unified PD Rating Scale (UPDRS) motor examination with sub-scores for the cardinal motor features of PD, grooved pegboard, and finger- and foot-tapping scores. Postural sway was also assessed. Patients on dopaminergic drugs were studied in the “off” state.

Results

Lower total striatal DAT binding was associated with higher UPDRS motor scores, slower performance on the grooved pegboard, and higher variability of postural sway. UPDRS subscale scores for rigidity and tremor, and footand finger tapping did not significantly correlate with striatal DAT binding. Thalamic DAT binding correlated with finger-tapping (r=0.532, p=0.005) and foot-tapping scores (r=0.474, p=0.017). Regional striatal analysis showed that ventral striatal DAT binding robustly correlated with UPDRS total motor (r=−0.507, p=0.007) and grooved pegboard (r=−0.567, p=0.002) performance. Posturography analysis showed increased sway variability with decreased posterior putamen DAT activity (r=−0.475, p=0.019).

Conclusion

These findings indicate that the nigrostriatal dopaminergic model of PD has limited correlations with the motor features of this disorder. Although nigrostriatal patterns of denervation may explain some of these findings, a more comprehensive model of parkinsonian motor impairments likely involves extra-striatal dopaminergic and non-dopaminergic mechanisms.

Keywords

Basal ganglia, thalamus, 11, dopamine, motor functions, Parkinson's disease, posturography