Cognitive Workload during Dual-tasking and its Relationship with Falls in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. Individuals with PD are at high risk of falling due to degeneration of dopaminergic and cholinergic pathways in the basal ganglia. The risk of falling increases when performing two tasks simultaneously, such as standing while talking. In such dual-tasking conditions, upright stance posture is an essential motor skill to accomplish various motor and cognitive tasks concurrently. Although maintaining an upright stance posture seems autonomous and effortless in healthy individuals, it may become challenging and cognitively effortful due to impaired autonomic control processes in individuals with PD. Dual-tasking deficiency is operationally defined as a decrease in motor or cognitive performance (or both) when tasks are performed concurrently. Dual-tasking deficiency is observed in all humans, but individuals with PD seem to be disproportionally affected by dual-tasking due to competition of limited cognitive resources. Dual-tasking is typically evaluated by dual-task cost on either cognitive tests or balance measures. However, these common endpoints have methodological limitations (ceiling/floor effect), they are not sensitive to change, and they do not explain the amount of cognitive workload needed to complete the tasks. Based on attention and effort theory, cognitive workload is defined as the mental effort that is needed to execute a task. Advances in neurophysiological technology enable us to measure cognitive workload in real-time. Pupillary response is a non-intrusive, real-time neurophysiological measure of cognitive workload. This dissertation project examined the neurophysiological response of the brain measured by pupillary response during dual-tasking conditions in individuals with PD. In Chapter 2, we conducted a systematic review to investigate the real-time brain activity during dual task gait and balance and whether changes in brain activity correlate with changes in behavioral outcomes in older adults and people with age-related neurodegenerative conditions. In Chapter 3, we investigated the usefulness of pupillary response to quantify the cognitive workload of postural control in healthy young adults. In Chapter 4, we examined the reliability and validity of pupillary response during dual-task balance conditions in individuals with PD. Finally, in Chapter 5, we conducted a study to investigate neurophysiological changes, indexed by pupillary response, during dual-task balance between three groups: PD fallers; PD non-fallers; and healthy controls. This body of research extends the use of pupillary response as a metric of cognitive workload during cognitive testing to cognitive-motor testing in a rehabilitation research setting. To our knowledge, this is the first study that investigated pupillary response as a metric of cognitive workload during dual-task balance in healthy adults and individuals with PD. Previous studies mainly used functional near-infrared spectroscopy or electroencephalogram as a neurophysiological tool to understand brain activity in aging and age-related neurodegenerative conditions. Pupillary response is cost-effective, less intrusive, and easy to implement in clinical settings compared to electroencephalogram and functional near-infrared spectroscopy. We found that pupillary response is a reliable and valid measure of cognitive workload during dual-task balance in both healthy adults and in individuals with PD. In addition, the findings of this research project demonstrated that individuals with PD exhibited higher cognitive workload measured by pupillary response compared to age- and sex-matched healthy controls during dual-task balance. Lastly, pupillary response significantly increased with increased task difficulty especially from single task to dual-task balance as well as from eyes open to eyes occluded conditions in both individuals with PD and healthy controls

Increased Postural Demand Is Associated With Greater Cognitive Workload in Healthy Young Adults: A Pupillometry Study

Introduction: Balance tasks require cognitive resources to ensure postural stability. Pupillometry has been used to quantify cognitive workload of various cognitive tasks, but has not been studied in postural control. The current investigation utilized pupillometry to quantify the cognitive workload of postural control in healthy young adults. We hypothesized that cognitive workload, indexed by pupil size, will increase with challenging postural control conditions including visual occlusion and cognitive dual tasking.Methods: Twenty-one young healthy adults (mean ± standard error of the mean), (age = 23.2 ± 0.49 years; 12 females) were recruited for this study. Participants completed four tasks: (1) standing with eyes open; (2) standing with eyes occluded (3) standing with eyes open while performing an auditory Stroop task; and (4) standing with eyes occluded while performing an auditory Stroop task. Participants wore eye tracking glasses while standing on a force platform. The eye tracking glasses recorded changes in pupil size that in turn were converted into the Index of Cognitive Activity (ICA). ICA values were averaged for each eye and condition. A two-way Analysis of Variance with post-hoc Sidak correction for pairwise comparisons was run to examine the effect of visual occlusion and dual tasking on ICA values as well on Center of Pressure (CoP) sway velocity in anterior–posterior (AP) and medio-lateral (ML) directions. A Pearson’s correlation coefficient was utilized to determine the relationship between ICA values and CoP sway velocity.Results: Significant within-condition effect was observed with visual occlusion for the right eye ICA values (p = 0.008). Right eye ICA increased from eyes open to eyes occluded conditions (p = 0.008). In addition, a significant inverse correlation was observed between right eye ICA values and CoP sway velocity in the ML direction across all the conditions (r = -0.25, p = 0.02).Conclusion: This study demonstrated support for increased cognitive workload, measured by pupillometry, as a result of changes in postural control in healthy young adults. Further research is warranted to investigate the clinical application of pupillometry in balance assessment

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study

The pupillary response reflects mental effort (or cognitive workload) during cognitive and/or motor tasks including standing postural control. EEG has been shown to be a non-invasive measure to assess the cortical involvement of postural control. The purpose of this study was to understand the effect of increasing postural task difficulty on the pupillary response and EEG outcomes and their relationship in young adults. Fifteen adults completed multiple trials of standing: eyes open, eyes open while performing a dual-task (auditory two-back), eyes occluded, and eyes occluded with a dual-task. Participants stood on a force plate and wore an eye tracker and 256-channel EEG cap during the conditions. The power spectrum was analyzed for absolute theta (4–7 Hz), alpha (8–13 Hz), and beta (13–30 Hz) frequency bands. Increased postural task difficulty was associated with greater pupillary response (p < 0.001) and increased posterior region alpha power (p = 0.001) and fronto-central region theta/beta power ratio (p = 0.01). Greater pupillary response correlated with lower posterior EEG alpha power during eyes-occluded standing with (r = −0.67, p = 0.01) and without (r = −0.69, p = 0.01) dual-task. A greater pupillary response was associated with lower CoP displacement in the anterior–posterior direction during dual-task eyes-occluded standing (r = −0.60, p = 0.04). The pupillary response and EEG alpha power appear to capture similar cortical processes that are increasingly utilized during progressively more challenging postural task conditions. As the pupillary response also correlated with task performance, this measurement may serve as a valuable stand-alone or adjunct tool to understand the underlying neurophysiological mechanisms of postural control

Pupillary Response to Cognitive Demand in Parkinson’s Disease: A Pilot Study

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Previous studies have shown that pupillary response, a physiological measure of cognitive workload, reflects cognitive demand in healthy younger and older adults. However, the relationship between cognitive workload and cognitive demand in Parkinson’s disease (PD) remains unclear. The aim of this pilot study was to examine the pupillary response to cognitive demand in a letter-number sequencing (LNS) task between 16 non-demented individuals with PD (age, median (Q1–Q3): 68 (62–72); 10 males) and 10 control participants (age: 63 (59–67); 2 males), matched for age, education, and Montreal Cognitive Assessment (MOCA) scores. A mixed model analysis was employed to investigate cognitive workload changes as a result of incremental cognitive demand for both groups. As expected, no differences were found in cognitive scores on the LNS between groups. Cognitive workload, exemplified by greater pupil dilation, increased with incremental cognitive demand in both groups (p = 0.003). No significant between-group (p = 0.23) or interaction effects were found (p = 0.45). In addition, individuals who achieved to complete the task at higher letter-number (LN) load responded differently to increased cognitive demand compared with those who completed at lower LN load (p < 0.001), regardless of disease status. Overall, the findings indicated that pupillary response reflects incremental cognitive demand in non-demented people with PD and healthy controls. Further research is needed to investigate the pupillary response to incremental cognitive demand of PD patients with dementia compared to non-demented PD and healthy controls. HIGHLIGHTS: - Pupillary response reflects cognitive demand in both non-demented people with PD and healthy controls - Although not significant due to insufficient power, non-demented individuals with PD had increased cognitive workload compared to the healthy controls throughout the testing - Pupillary response may be a valid measure of cognitive demand in non-demented individuals with PD - In future, pupillary response might be used to detect cognitive impairment in individuals with P

Exercise interventions for older adults with Alzheimer's disease: a systematic review and meta-analysis protocol

BACKGROUND: The growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. METHODS: This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. DISCUSSION: This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175016