Methodological considerations of evaluating the rate of presynaptic dopaminergic denervation in Parkinson disease with radiotracers: Analysis of the PPMI data

Many previous studies have estimated the rate of dopaminergic denervation in Parkinson disease (PD) via imaging studies. However, they lack the considerations of onset age, disease duration at onset, gender, and dopaminergic denervation due to normal aging. Herein, using a large prospective cohort, we estimated the rate of dopaminergic denervation in PD patients, compared with an age- and gender-matched normal control group. One hundred forty-one normal controls and 301 PD patients were enrolled. Striatal specific binding ratios (SBRs) of I-123 FP-CIT single positron emission tomography images were analyzed according to the age of onset, gender, and the duration of motor symptoms. In the PD group, symptom duration was significantly correlated with caudate SBRs, but with putamen SBRs (P < .05, R(2) = 0.02). Moreover, was significantly inversely related to caudate SBRs, but not with putamen SBRs (P < .05, R(2) = 0.02). Patients of different age onsets did not show any significant correlation between symptom durations and striatal SBRs. In the age-matched group, no significant relationship was observed between symptom duration and percent decrease of caudate SBRs, but there was a significant relationship between symptom duration and percent decrease of the putamen SBRs (P < .01, R(2) = 0.06). There was no significant relationship between the symptom duration and the percent decrease of striatal SBRs in the age- and gender-matched group. The significance and R(2) values from the regression analysis between symptom duration, age, and dopaminergic denervation are low. This suggests that, contrary to previous knowledge, there is a relatively weak association between dopaminergic denervation and age or symptom duration.