Gait Disturbance Associated with Cholinergic Dysfunction in Early Parkinson's Disease

Objective: The pathophysiology of gait disturbance in early Parkinson’s disease (PD) is not fully understood, but cholinergic dysfunction may be associated with gait disturbance. Central cholinergic activity is closely related with olfaction in PD and it can be estimated with short-latency afferent inhibition (SAI). We hypothesize that cholinergic dysfunction, especially olfactory dysfunction, could be associated with gait disturbance in early PD. Methods: A total of 57 early PD patients were enrolled. Olfaction was examined using the Korean version of the Sniffin’ stick (KVSS) test. The PD patients were grouped as anosmia, hyposmia and normosmia according to the KVSS score. The gait parameters examined during 10 m of gait. SAI was measured by conditioning motor-evoked potentials, elicited by single transmagnetic stimulation (TMS) of the motor cortex, with electrical stimuli delivered to the contralateral median nerve at intervals ranging from N20 to N20+4 ms. Results: The SAI response (N20 to N20+4 ms) and integrated SAI were less inhibited in PD for the anosmia and hyposmia groups than for the normosmia group (for all values, p<0.01). In the PD anosmia group, the walking time was longer and more steps were taken during the 10 m gait than in the PD hyposmia and normosmia groups (p=0.01, p<0.01). In addition, gait speed was slower and stride length was shorter in the PD anosmia group than in the other groups (p=0.01, p<0.01). The TDI score was an independent factor that showed a correlation (R2=0.261, 0.257) with gait speed in PD patients. A reduced TDI score was an independent determinant of reduced gait speed, explaining 25% of the variability even after correction of various factors related to cholinergic dysfunction. Conclusion: Central cholinergic system influences cognition, gait, and olfaction in the early stage of PD.