Bradykinesia in Alzheimer's disease and its neurophysiological substrates

Objective: Alzheimer's disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer's disease. Methods: Twenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation. Results: Patients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer's disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery. Conclusion: This study provides new information on the pathophysiology of altered voluntary movements in Alzheimer's disease. Significance: The study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer's disease.