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Background: Gait disturbance is an early, disabling feature of Parkinson's disease (PD) that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease‐specific gait impairment. Objective: To evaluate associations between sub‐regional cholinergic basal forebrain volumes and longitudinal progression of gait impairment in PD. Methods: 99 PD participants and 47 control participants completed gait assessments via an instrumented walkway during 2 minutes of continuous walking, at baseline and for up to 3 years, from which 16 spatiotemporal characteristics were derived. Sub‐regional cholinergic basal forebrain volumes were measured at baseline via MRI and a regional map derived from post‐mortem histology. Univariate analyses evaluated cross‐sectional associations between sub‐regional volumes and gait. Linear mixed‐effects models assessed whether volumes predicted longitudinal gait changes. Results: There were no cross‐sectional, age‐independent relationships between sub‐regional volumes and gait. However, nucleus basalis of Meynert volumes predicted longitudinal gait changes unique to PD. Specifically, smaller nucleus basalis of Meynert volume predicted increasing step time variability (P = 0.019) and shortening swing time (P = 0.015); smaller posterior nucleus portions predicted shortening step length (P = 0.007) and increasing step time variability (P = 0.041). Conclusions: This is the first study to demonstrate that degeneration of the cortical cholinergic system predicts longitudinal progression of gait impairments in PD. Measures of this degeneration may therefore provide a novel biomarker for identifying future mobility loss and falls. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of 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]