Attentional Control of Gait and Falls: Is Cholinergic Dysfunction a Common Substrate in the Elderly and Parkinson’s Disease?

Abstract

The aim of this study was to address whether deficits in the central cholinergic activity may contribute to the increased difficulty to allocate attention during gait in the elderly with heightened risk of falls. We recruited 50 participants with a history of two or more falls (33 patients with Parkinson’s Disease and 17 older adults) and 14 non-fallers age-matched adults. Cholinergic activity was estimated by means of short latency afferent inhibition (SAI), a transcranial magnetic stimulation (TMS) technique that assesses an inhibitory circuit in the sensorimotor cortex and is regarded as a global marker of cholinergic function in the brain. Increased difficulty to allocate attention during gait was evaluated by measuring gait performance under single and dual-task conditions. Global cognition was also assessed. Results showed that SAI was reduced in patients with PD than in the older adults (fallers and non-fallers) and in older adults fallers with respect to non-fallers. Reduction in SAI indicates less inhibition i.e., less cholinergic activity. Gait speed was reduced in the dual task gait compared to normal gait only in our faller population and changes in gait speed under dual task significantly correlated with the mean value of SAI. This association remained significant after adjusting for cognitive status. These findings suggest that central cholinergic activity may be a predictor of change in gait characteristics under dual tasking in older adults and PD fallers independently of cognitive status.

Global cognitive function and processing speed are associated with gait and balance dysfunction in Parkinson’s disease

“…This pilot study adds to the body of evidence [5, 7, 28–30] that lower global cognitive function is correlated with worse performance in different domains of gait and balance. Importantly, this is the first study to demonstrate the correlation between reduced processing speed and impaired turning.…”

Reducing falls in Parkinson's disease: interactions between donepezil and the 5‐HT6 receptor antagonist idalopirdine on falls in a rat model of impaired cognitive control of complex movements

“…Striatal dopamine loss, in general terms, yields impairments in action selection and sequencing, and decreases in movement vigor and velocity (e.g., Gepshtein et al, 2014;Rueda-Orozco & Robbe, 2015;Yttri & Dudman, 2016). Thus, combined cholinergic-dopaminergic losses have been hypothesized to render striatal circuitry largely incapable of integrating information about ongoing behavior which, in interaction with poor habitual action control, gives rise to major gait and balance errors, ineffective movement recovery after errors, and thus falls (Sarter et al, 2014a;Pelosin et al, 2016).…”

Reducing falls in a model of impaired cognitive control of movement (Commentary on Kucinski et al.)

“…() established a model whereby lesions of dopaminergic terminals in the dorsal striatum along with lesions of basal forebrain corticopetal cholinergic neurons increased the rate of falls by rats in a motor task that varied demands to maintain balance and included presentation of distracting stimuli. Importantly, other studies in humans also provide evidence that dysfunctional cholinergic activity contributes to an increase in falls in patients with Parkinson's disease and in the elderly, supporting the translational potential of the animal model (Pelosin et al ., ). The next step, described in the paper in this issue by Kucinski et al ., is to test whether treatments that target depressed cortical cholinergic function attenuate the increased fall rate in this animal model.…”

“…Thus, challenges to the limits of attentional processing, such as distracting stimuli, may limit the ability to attend and make adjustments in order to maintain balance, thereby increasing the likelihood of falls. More recent experiments have focused on attentional deficits in conditions such as Parkinson's disease, associated with motor deficits and increased risk of falls (Pelosin et al, 2016). This mounting evidence leads to the conclusion that drug treatments that facilitate attentional processing may decrease the risk of falls.A next step in this area is to identify relevant underlying mechanisms involved in motor control and attention, assess changes in the brain regions in relevant conditions such as Parkinson's disease and then evaluate whether treatments that facilitate attentional processing can decrease the rate of falls.…”

“…Thus, challenges to the limits of attentional processing, such as distracting stimuli, may limit the ability to attend and make adjustments in order to maintain balance, thereby increasing the likelihood of falls. More recent experiments have focused on attentional deficits in conditions such as Parkinson's disease, associated with motor deficits and increased risk of falls (Pelosin et al, 2016). This mounting evidence leads to the conclusion that drug treatments that facilitate attentional processing may decrease the risk of falls.…”