Cholinergic degeneration marks gait speed in Parkinson’s patients

By Eleanor McDermid, Senior medwireNews Reporter

Gait speed is preserved in patients with Parkinson’s disease (PD) who have isolated dopaminergic denervation, but reduced in those with comorbid cholinergic denervation, research shows.

“We do not suggest that basal forebrain cholinergic degeneration is the sole mechanism of decline of gait function in PD,” say study author Nicolaas Bohnen (University of Michigan, Ann Arbor, USA) and team.

But they say their findings are in line with the hypothesis that “the clinical heterogeneity of PD results from variable involvement of different brain systems.”

They add: “These results provide support for the notion that emergence of dopamine nonresponsive gait problems in PD reflects transitions from a predominantly hypodopaminergic disorder to a multisystem neurodegenerative disorder.”

All of the 125 PD patients in the study had nigrostriatal (ie, dopaminergic) denervation, but only 38 had cholinergic degeneration, assessed on positron emission tomography and defined as being below the fifth percentile of values in a control group of 32 people of similar age to the patients.

The average gait speed among patients with isolated dopaminergic denervation was 1.12 m/s, which was not significantly slower than the 1.17 m/s seen in the control group. By contrast, the average gait speed was 0.97 m/s among patients with comorbid cholinergic degeneration. This difference was significant after accounting for age, gender, and global cognition.

The team notes that cognitive function is closely associated with gait speed in both PD patients and healthy elderly people, suggesting that the association between cholinergic denervation and gait “may reflect the impact of impaired cognitive processing during ambulation.”

Indeed, global cognitive z scores were lower in patients with cholinergic degeneration (–0.81) than in those with isolated dopaminergic degeneration (–0.21) and controls (0.06), and had a significant influence on gait speed among all study participants.

“Degraded striatal function in PD likely places additional burdens on other brain systems, including those mediating cognitive functions,” say the researchers in Neurology.

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