Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

• Published in: Clinical neurophysiology Vol. 131; no. 4; pp. 850 - 858
• Main Authors: Bologna, Matteo, Guerra, Andrea, Colella, Donato, Cioffi, Ettore, Paparella, Giulia, Di Vita, Antonella, D'Antonio, Fabrizia, Trebbastoni, Alessandro, Berardelli, Alfredo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2020
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - physiopathology; Alzheimer’s disease; Bradykinesia; Cholinergic system; Evoked Potentials, Motor - physiology; Female; Humans; Hypokinesia - complications; Hypokinesia - physiopathology; Kinematic analysis; Male; Middle Aged; Motor control; Motor Cortex - physiopathology; Movement - physiology; Neurology; Neuronal Plasticity - physiology; Primary motor cortex; Transcranial Magnetic Stimulation; PAS; M1; BDI; I/O; LTP; ANOVA; MMSE; Bradykinesia; SICI; Kinematic analysis; EMG; ISI; AD; Alzheimer’s disease; FAB; FSS; AMT; Cholinergic system; iTBS; Motor control; Primary motor cortex; CV; PD; RMT; MEP; SAI; HC; TMS; MDS-UPDRS; resting motor threshold; short-interval intracortical inhibition; active motor threshold; transcranial magnetic stimulation; inter-stimulus interval; Mini Mental State Examination; Fatigue Severity Scale; long-term potentiation; Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale; Frontal Assessment Battery; analysis of variance; healthy controls; motor-evoked potentials; paired associative stimulation; intermittent theta burst stimulation; Alzheimer's Disease; electromyography; short-latency afferent inhibition; Parkinson’s disease; Beck Depression Inventory; coefficient of variation; input-output
• ISSN: 1388-2457; 1872-8952; 1872-8952
• DOI: 10.1016/j.clinph.2019.12.413

•Clinical observations indicate that bradykinesia can be observed in Alzheimer’s disease (AD).•We here found that movement slowness in AD correlates with measures of cholinergic dysfunction.•This study provides information on the pathophysiology of altered voluntary motor control in AD. 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. 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. 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. This study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease. The study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.