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Free-water imaging can predict and monitor dopamine system degeneration in people with Parkinson's disease. It can also enhance the sensitivity of traditional diffusion tensor imaging (DTI) metrics for indexing neurodegeneration. However, these tools are yet to be applied to investigate cholinergic system degeneration in Parkinson's (which involves both the pedunculopontine nucleus (PPN) and cholinergic basal forebrain (cBF)). Free-water imaging, free-water-corrected DTI, and volumetry were used to extract structural metrics from the cBF and PPN in 99 people with Parkinson's and 46 age-matched controls. Cognitive ability was tracked over 4.5-years. Pearson's partial correlations revealed that free-water-corrected DTI metrics in the PPN were associated with performance on cognitive tasks that required participants to make rapid choices (behavioural flexibility). Volumetric, free-water content and DTI metrics in the cBF were elevated in a sub-group of people with Parkinson's with evidence of cognitive impairment, and linear mixed modelling revealed that these metrics were differently associated with current and future changes to cognition. Free water and free-water-corrected DTI can index cholinergic degeneration that could enable stratification of patients in clinical trials of cholinergic interventions for cognitive decline. In addition, degeneration of the PPN impairs behavioural flexibility in Parkinson's, which may explain this region's role in increased risk of falls.

Free-water imaging can predict and monitor dopamine system degeneration in people with Parkinson's disease. It can also enhance the sensitivity of traditional diffusion tensor imaging (DTI) metrics for indexing neurodegeneration. However, these tools are yet to be applied to investigate cholinergic system degeneration in Parkinson's (which involves both the pedunculopontine nucleus (PPN) and cholinergic basal forebrain (cBF)). Free-water imaging, free-water-corrected DTI, and volumetry were used to extract structural metrics from the cBF and PPN in 99 people with Parkinson's and 46 age-matched controls. Cognitive ability was tracked over 4.5-years. Pearson's partial correlations revealed that free-water-corrected DTI metrics in the PPN were associated with performance on cognitive tasks that required participants to make rapid choices (behavioural flexibility). Volumetric, free-water content and DTI metrics in the cBF were elevated in a sub-group of people with Parkinson's with evidence of cognitive impairment, and linear mixed modelling revealed that these metrics were differently associated with current and future changes to cognition. Free water and free-water-corrected DTI can index cholinergic degeneration that could enable stratification of patients in clinical trials of cholinergic interventions for cognitive decline. In addition, degeneration of the PPN impairs behavioural flexibility in Parkinson's, which may explain this region's role in increased risk of falls.

Background: Although laboratory studies demonstrate that training programmes using auditory rhythmical cueing (ARC) may improve gait post-stroke, few studies have evaluated this intervention in the home and outdoors where deployment may be more appropriate. This manuscript reports stakeholder refinement of an ARC gait and balance training programme for use at home and outdoors, and a study which assessed acceptability and deliverability of this programme. Methods: Programme design and content were refined during stakeholder workshops involving physiotherapists and stroke survivors. A two-group acceptability and deliverability study was then undertaken. Twelve patients poststroke with a gait related mobility impairment received either the ARC gait and balance training programme or the gait and balance training programme without ARC. Programme provider written notes, participant exercise and fall diaries, adverse event monitoring and feedback questionnaires captured data about deliverability, safety and acceptability of the programmes. Results: The training programme consisted of 18 sessions (six supervised, 12 self-managed) of exercises and ARC delivered by a low-cost commercially available metronome. All 12 participants completed the six supervised sessions and 10/12 completed the 12 self-managed sessions. Provider and participant session written records and feedback questionnaires confirmed programme deliverability and acceptability. Conclusion: An ARC gait and balance training programme refined by key stakeholders was feasible to deliver and acceptable to participants and providers.