Gait speed in Parkinson disease correlates with cholinergic degeneration

Objective: We investigated dopaminergic and cholinergic correlates of gait speed in Parkinson disease (PD) and non-PD control subjects to test the hypothesis that gait dysfunction in PD may result from multisystem degeneration. Methods: This was a cross-sectional study. Subjects with PD but without dementia (n =125, age 65.6 +/- 7.3 years) and elderly subjects without PD (n = 32, age 66.0 +/- 10.6 years) underwent [C-11] dihydrotetrabenazine dopaminergic and [C-11] methyl-4-piperidinyl propionate acetylcholinesterase PET imaging, and cognitive and clinical testing, including an 8.5-m walk in the dopaminergic "off" state. The fifth percentile of cortical cholinergic activity in the elderly without PD was used to define normal-range activity in the subjects with PD. Results: Normal-range cortical cholinergic activity was present in 87 subjects with PD (69.6%). Analysis of covariance using gait speed as the dependent variable demonstrated a significant model (F = 6.70, p < 0.0001) with a significant group effect (F = 3.36, p = 0.037) and significant slower gait speed in the low cholinergic PD subgroup (0.97 +/- 0.22 m/s) with no significant difference between the normal-range cholinergic PD subgroup (1.12 +/- 0.20 m/s) and control subjects (1.17 +/- 0.18 m/s). Covariate effects were significant for cognition (F = 6.58, p = 0.011), but not for striatal dopaminergic innervation, sex, or age. Conclusion: Comorbid cortical cholinergic denervation is a more robust marker of slowing of gait in PD than nigrostriatal denervation alone. Gait speed is not significantly slower than normal in subjects with PD with relatively isolated nigrostriatal denervation.