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 11C-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 foot- and 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: 11C-β-CFT PET; Basal ganglia; Parkinson’s disease; dopamine; motor functions; posturography; thalamus.