Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET.

PURPOSE: Dynamic [ 11 C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinson's disease (PD). We investigated whether these complementary biomarkers could explain a higher percentage of motor symptom severity variation in PD and inform other PD-specific physiological alterations and symptomatology.

METHODS

Binding potential ( BP ND ) and relative perfusion ( R 1 ) images were derived 30 PD and 30 controls imaged with [ 11 C]UCB-J PET. A spatial covariance analysis was used on R 1 to derive PDRP-a known metabolic network alteration in PD. Linear models related PD-motor symptom severity to PDRP expression and nigral synaptic losses. Next, whole-brain cluster analyses identified physiological correlates for PD-tremor severity, a prominent motor symptom that does not correlate with dopaminergic losses. Lastly, inter-individual regional correlation alterations in PD were examined for both BP ND and R 1 .

RESULTS

PDRP was identified from R 1 , with higher expression in PD ( p =1.7×10 -5 , Cohen's d =1.2), and its expression correlated with MDS-UPDRS III ( r =0.57, p =0.0009). Combining PDRP expression scores with synaptic density in the substantia nigra explained 48% of the total variation in MDS-UPDRS Part III, twice as much as previously reported using nigral synaptic density alone. Two significant large clusters ( p k <1×10 -6 ) were identified in the occipital-parietal areas where R 1 was negatively correlated with tremor severity ( r ∼ -0.65, p <0.001). Extensive correlation alterations were observed in synaptic density (prominently involving pallidum) and perfusion (prominently involving thalamus).

CONCLUSIONS

Combining synaptic and perfusion outcomes for [ 11 C]UCB-J PET explains more physiological alterations associated with PD.