Cholinergic dysfunction contributes to gait disturbance in early Parkinson's disease

• DOI: 10.1093/brain/aws207
• Publication Date: 2012-09-08T03:04:46Z
• Authors: L. Rochester; A. J. Yarnall; M. R. Baker; R. V. David; S. Lord; B. Galna; D. J. Burn
• Keywords: Gait Disturbance

Gait disturbance is an early feature in Parkinson's disease. Its pathophysiology poorly understood; however, cholinergic dysfunction may be a non-dopaminergic contributor to gait. Short-latency afferent inhibition surrogate measure of activity, allowing the contribution gait evaluated. We hypothesized that short-latency would independent predictor Twenty-two participants with disease and 22 age-matched control subjects took part study. was measured objectively using instrumented walkway (GAITRite), were asked walk at their preferred speed for 2 min around 25-m circuit. Spatiotemporal characteristics (speed, stride length, time step width) dynamics (variability described as within subject standard deviation of: speed, time, length determined. by conditioning motor evoked potentials, elicited transcranial magnetic stimulation cortex, electrical stimuli delivered contralateral median nerve intervals ranging from N20 (predetermined) + 4 ms. determined percentage difference between test conditioned response all group mean. Participants optimally medicated testing. had significantly reduced (P = 0.002), 0.008) 0.001). also 0.004). In disease, but not subjects, significant associations found inhibition, age postural instability disorder score (Movement Disorders Society Unified Disease Rating Scale) attention, whereas global cognition depression marginally significant. No other variables associated inhibition. A multiple hierarchical regression model explored controlling age, posture symptoms (Postural Instability Disorder score-Movement Scale), attention depression. Regression analysis showed slower explaining 37% variability. The final explained 72% variability only emerging determinants. results suggest important findings point non-motor mechanisms dysfunction. Our study provides new insights into underlying dysfunction, help direct future therapeutic approaches.