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

Abstract

Purpose Dynamic [11C]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 (BPND) and relative perfusion (R1) images were derived 30 PD and 30 controls imaged with [11C]UCB-J PET. A spatial covariance analysis was used on R1 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 BPND and R1. Results PDRP was identified from R1, with higher expression in PD (p=1.7x10-5, 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 (pk<1x10-6) were identified in the occipital-parietal areas where R1 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 [11C]UCB-J PET explains more physiological alterations associated with PD.