Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study

Purpose Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [ 11 C]HED PET in PD. Methods Retrospective database analysis of 27 PD patients with cardiac sympathetic denervation. All patients underwent spatiotemporal kinematic gait assessment (medication ‘off’ state), cardiac [ 11 C]HED and dopaminergic brain [ 11 C]DTBZ PET scans. We employed a hierarchical regression approach to examine associations between the extent of cardiac denervation, dopaminergic nigrostriatal neurodegeneration, and three gait parameters - velocity, step length and cadence. Results More extensive cardiac denervation was associated with slower velocity (estimate: -1.034, 95% CI [-1.65, -0.42], p = 0.002), shorter step length (estimate: -0.818, 95% CI [-1.43, -0.21], p = 0.011) and lower cadence (estimate: -0.752, 95% CI [-1.28, -0.23], p = 0.007) explaining alone 30% (Adjusted-R²: 0.297), 20% (Adjusted-R²: 0.202) and 23% (Adjusted-R²: 0.227) of the variability, respecivetly. These associations remained independent of striatal dopaminergic impairment and confounding factors such as age, Hoehn and Yahr (HY) stages, peripheral neuropathy, cognition, and autonomic symptoms. In contrast, striatal dopaminergic denervation was significantly associated with step length (estimate: 0.883, 95% CI [0.29, 1.48], p = 0.005), explaining about 24% of the variability but was dependent of HY stage. Conclusions More severe cardiac noradrenergic denervation was associated with lower gait velocity, independent of striatal dopaminergic denervation and HY stage, impacting both step length and cadence. These results suggest independent contributions of the peripheral autonomic system degeneration on gait dynsfunction in PD.