Cholinergic and dopaminergic PET imaging of gait in Parkinson disease

Objectives To investigate the relationship between gait, striatal binding of [¹¹C]-dihydrotetrabenazine (DTBZ), and thalamic and cerebellar [¹¹C]-methyl-4-piperidinyl propionate (PMP) activity in Parkinson disease (PD) patients.

Methods Mild to moderate PD patients (N =28; 0 F; 69.1 ± 7.6 yrs; H & Y 1-3) underwent [¹¹C]DTBZ and [¹¹C]PMP PET brain imaging and gait assessment. Temporal gait parameters (Gait Speed, Cadence, Step Time, Stance Time, and Swing Time) were acquired with a pressure-sensitive foot sensor system (Biopac). DTBZ PET data were analyzed using bolus-infusion equilibrium kinetic modeling with the global neocortex as reference region. PMP uptake ratio was calculated as late versus early radiotracer retention. Temporal gait parameters, striatal DTBZ distribution volume (DV), and cerebellar and thalamic PMP uptake ratio were statistically correlated (Spearman).

Results Decreased cerebellar PMP uptake ratio was associated with decreased cadence (ρ=0.440, p=0.022) and increased step time (ρ=-0.501, p=0.008) and swing time (ρ=-0.525, p=0.005). Decreased thalamic PMP uptake ratio was associated with increased step time (ρ=-0.402, p=0.038) and borderline significant with decreased cadence (ρ=0.362, p=0.097). There were no significant correlations between any of the temporal gait parameters and DTBZ-DV.

Conclusions Unlike dopaminergic denervation of the striatum, cholinergic denervation of the cerebellum and the thalamus correlates with temporal aspects of gait in PD patients. PD patients take fewer steps per minute and step time and leg swing time increases. These temporal effects are especially correlated with cerebellar cholinergic denervation. The cerebellum is an important center for timing and mobility control. The thalamus receives cholinergic projections from the pedunculopontine nucleus, an important locomotor center in the brain stem. Cholinergic denervation of the cerebellum and thalamus, rather than striatal dopaminergic denervation, appears to affect these aspects of gait in PD.

Research Support Department of Veterans Affair