To determine the relationship between cholinergic nucleus 4 (Ch4) grey matter density (GMD) and gait in patients with Parkinson’s disease (PD).

There is substantial evidence that cholinergic basal forebrain degeneration contributes to both cognitive and motor symptoms in PD. Specifically, cortical cholinergic denervation has been implicated in slowed gait speed. We investigated whether reduced Ch4 GMD, indicating degeneration of cholinergic neurons that project to the neocortex, was associated with reduced fast walking speed in PD.

We investigated 66 PD patients from the University of Virginia who had brain MRI and formal gait testing as part of an evaluation prior to their first neurosurgical procedure. Using probabilistic maps of the cholinergic basal forebrain, Ch4 and cholinergic nuclei 1, 2, and 3 (Ch123) densities were calculated for each MRI. Bilateral cortical GMD was separately determined.

After adjusting for age, Ch4 GMD was a significant predictor of fast walking speed in the “on” state (FWSON) (p=0.004), while Ch123 GMD was not a significant predictor of FWSON (p=0.106). Bilateral cortical GMD was a significant predictor of FWSON after adjustment for age (p=0.009) but not if adjusted for Ch4 GMD (p=0.44). After adjustment for age, Ch4 GMD was not significantly associated with timed up and go (TUG) in the “on” state (p=0.068) or the cognitive TUG in the “on” state (p=0.344).  However, Ch4 GMD was significantly associated with % worsening in TUG with the addition of a dual task (p=0.021).

Cholinergic basal forebrain degeneration as measured by reduced Ch4 GMD is associated with slower gait speed in PD. Greater worsening on the TUG with a dual task is also associated with reduced Ch4 GMD. Cholinergic therapies have the potential to treat aspects of gait impairment in PD not addressed by dopaminergic therapies.