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Degradation of striatal dopamine in Parkinson's disease (PD) may initially be supplemented by increased cognitive control mediated by cholinergic mechanisms. Shift to cognitive control of walking can be quantified by prefrontal cortex activation. Levodopa improves certain aspects of gait and worsens others, and cholinergic augmentation influence on gait and prefrontal cortex activity remains unclear. This study examined dopaminergic and cholinergic influence on gait and prefrontal cortex activity while walking in PD. A single‐site, randomized, double‐blind crossover trial examined effects of levodopa and donepezil in PD. Twenty PD participants were randomized, and 19 completed the trial. Participants were randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments, with 2 weeks with treatment and a 2‐week washout. The primary outcome was change in prefrontal cortex activity while walking, and secondary outcomes were change in gait and dual‐task performance and attention. Levodopa decreased prefrontal cortex activity compared with off medication (effect size, −0.51), whereas the addition of donepezil reversed this decrease. Gait speed and stride length under single‐ and dual‐task conditions improved with combined donepezil and levodopa compared with off medication (effect size, 1 for gait speed and 0.75 for stride length). Dual‐task reaction time was quicker with levodopa compared with off medication (effect size, −0.87), and accuracy improved with combined donepezil and levodopa (effect size, 0.47). Cholinergic therapy, specifically donepezil 5 mg/day for 2 weeks, can alter prefrontal cortex activity when walking and improve secondary cognitive task accuracy and gait in PD. Further studies will investigate whether higher prefrontal cortex activity while walking is associated with gait changes. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Cumulative dementia incidence in Parkinson's disease (PD) is significant, with major personal and socioeconomic impacts on individuals with PD and their carers. Early identification of dementia risk is vital to ensuring optimal intervention. Saccadic deficits often distinguish neurodegenerative disorders and cognitive impairment, but their ability to predict cognitive decline in PD has yet to be determined. The aims of this study were to (1) evaluate baseline (6.4 ± 6.1 months since PD diagnosis) differences in pro-saccadic metrics between those with early PD and healthy age-matched adults; and (2) assess the ability of baseline pro-saccades to predict subsequent cognitive decline over 4.5 years.Methods: One hundred and forty-one PD and 90 age-matched participants recruited at diagnosis underwent saccadometric assessment of pro-saccades at baseline and had cognition assessed at baseline, 18, 36, and 54 months. Pro-saccadic characteristics included latency, duration, amplitude, peak, and average velocity. Cognitive assessment included executive function, attention, fluctuating attention, and memory. Linear mixed-effects models examined pro-saccadic metrics as predictors of cognitive decline over 54 months.Results: Pro-saccades were significantly impaired at baseline in PD compared with controls. Pro-saccadic characteristics of latency, duration, peak, and average velocity predicted decline in global cognition, executive function, attention, and memory over 54 months in PD. In addition, only reduction in global cognition and attention were predicted by pro-saccadic metrics in age-matched adults, indicating that PD findings were not purely age related.Conclusions: Saccadic characteristics are impaired in early PD and are predictive of cognitive decline in several domains. Assessment of saccades may provide a useful non-invasive biomarker for long-term PD cognitive decline in early disease. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Abstract: Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real‐time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye‐tracker measured saccade frequency during gait in 55 people with PD and 32 age‐matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual‐task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual‐task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development. [ABSTRACT FROM AUTHOR]

Gait impairment is a core feature of Parkinson's disease ( PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real-time cognitive and visual processes and their impact on gait when walking. This study explored: (i) saccade frequency when walking under different attentional manipulations of turning and dual-task; and (ii) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye movements per-second) was measured during gait in 60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual-task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research. [ABSTRACT FROM AUTHOR]