Gait impairment is a major symptom of Parkinson disease (PD) and is associated with increased risk of falls, loss of independence, and reduced quality of life.1 , 2 Despite the benefits of dopamine replacement therapy, dysfunctional gait characteristics are only partially responsive. Furthermore, medication efficacy declines and gait dysfunction becomes increasingly evident as the disease progresses.3 , 4 Thus, additional therapeutic strategies are needed to help improve gait in people with PD. Cueing is a well-established component of gait rehabilitation in management of PD, which provides an external stimulus to improve gait. External stimuli include auditory cues (eg, a rhythmic beat such as a metronome), visual cues (eg, striped lines on the floor to step over), or tactile cues (eg, a vibratory stimulus). In particular, auditory cues demonstrate evidence for efficacy,5 , 6 showing beneficial effects for characteristics of gait including step velocity, step length, cadence, and variability.5 , 7–11 Although clinical trials have established efficacy, it remains unclear as to which stage of disease the intervention should be introduced.
To address this question and inform clinical practice, longitudinal studies are needed to compare changes in gait response to a cue with respect to disease progression. In very early PD, external cueing may not be necessary because attention can be used to effectively compensate for basal ganglia dysfunction; under these circumstances it could be hypothesized that cues may act as a distraction (dual-task). However, there are few studies that have assessed the effect of auditory cueing in early disease to address this hypothesis. In comparison, as disease progresses, compensatory control of gait may be less effective and therefore external cueing can be used effectively to take over an executive/attentional role.8 , 12 , 13 Therefore, the timing of cues may be important, and it is valuable to establish an optimal therapeutic window to improve clinical care.
We aimed to examine the effect of auditory cues on gait characteristics in people with early PD at 2 time points, 3 years apart. We explored (1) the immediate effect of auditory cues on gait in participants with early PD cohort compared with healthy older adults; and 2) the change in response to auditory cues in a subset of participants with PD 3 years later. We hypothesized that response to auditory cues in early disease would be similar to that of healthy controls, and that response to an auditory cue in people with PD would increase as disease progressed due to loss of compensatory control.
Participants with idiopathic PD and healthy older adults were recruited to the study. People with PD were recruited within 6 months of diagnosis of idiopathic PD as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation-Parkinson's disease (ICICLE-PD) study.14 Participants were included if idiopathic PD was diagnosed by a movement disorders specialist according to the UK Parkinson's disease Brain Bank Criteria.15 Participants were excluded if they had with significant memory impairment (Mini-Mental State Examination ≤24), dementia with Lewy bodies, drug-induced parkinsonism, vascular parkinsonism, progressive supranuclear palsy, multiple-system atrophy, corticobasal degeneration, or a poor command of English (defined as being unable to perform the assessments and questionnaires in the opinion of the assessor).
Healthy older adults were recruited from community sources and inclusion criteria included older than 60 years, able to walk independently, had no significant cognitive impairment, and no mood or movement disorders. The study was approved by the Newcastle and North Tyneside Research Ethics Committee and all participants gave informed consent. Full details regarding recruitment have been described previously.14
Clinical and Demographic Assessments
Age, gender, height, and weight were reported for all participants. Disease severity was assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part III,16 and the Hoehn and Yahr (H&Y) scale.17 Global cognition was assessed using the Montreal Cognitive Assessment (MoCA),18 depression was measured using the Geriatric Depression Scale (GDS-15),19 and attention with the Power of Attention test (POA). The POA is a composite score from the Cognitive Drug Research computerized battery20 , 21 and is determined as the total response of 3 assessments—simple reaction time, choice reaction time, and digit vigilance—with a higher score indicating worse attention. Levodopa-equivalent daily dose (LEDD) scores were also calculated for each participant.22
Participants were asked to walk at a comfortable pace for 4 trials of 10 m each. During the 10 m the participants walked over a 7-m × 0.6-m instrumented mat (GAITRite), with 1.5-m acceleration and deceleration allocated at either end. Participants completed the 4 trials of 10-m walks under 2 conditions: with and without an auditory cue. For the baseline condition (no cue), participants were asked to walk at their comfortable walking pace and to concentrate on their walking. Following baseline assessment, participants were provided with a metronome beat set at their individualized cadence (as measured during the baseline condition) and were instructed “to take a big step in time to the beat.” The metronome beat was started a few seconds before the participant began walking, and 4 trials of 10 m were completed with the auditory cue. Four trials were performed for each condition, with the first trial excluded to remove practice effects; participants were not exposed to the auditory cue prior to these trials. Five gait characteristics known to be responsive to external cueing techniques were collected: step velocity, step length, step time, step length variability, and step time variability.10 , 12 , 23 For our exploratory longitudinal study, all assessments were conducted in a subset of 9 participants with PD 3 years later (see Figure 1). Participants with PD were assessed on-medication, defined as within 1 hour of medication intake.
Data were analyzed using SPSS v24. A P value of ≤ 0.05 was considered statistically significant for all analyses.
Cross Sectional Analysis
Data were initially inspected for distribution using the Shapiro-Wilks test. Demographic, clinical, and cognitive variables for participants with PD and healthy older controls were compared using independent t tests or chi-squared tests where appropriate. Measures of step time variability were log transformed due to nonnormal distribution. The effect of auditory cueing on gait in participants with PD compared with healthy older adults was assessed using repeated-measures analysis of variance with groups as a between-subject factor and the task condition as a repeated-measures factor (no cue and cue).
Demographic, clinical, and cognitive variables of the subset of participants with PD included in the follow-up analyses were compared using Wilcoxon tests. The effect of auditory cue in the subset of participants with PD (n = 9) after 3 years was assessed using Wilcoxon tests.
Participants with PD (n = 25) and healthy older adults (n = 29) were similar in age, gender, height, and weight (see Table 1). For the clinical characteristics, people with PD and healthy older adults were similar in the POA (PD: 1299.3 ± 164.6; healthy: 1252.7 ± 114.4), MoCA (PD: 27.3 ± 2.88; healthy: 27.3 ± 2.11), and GDS (PD: 1.6 ± 1.49; healthy: 0.9 ± 1.54). Participants with PD had a mean LEDD of 349.23 ± 200.79. During usual walking (without cue), participants with PD and healthy older adults had similar gait performance.
Effect of Auditory Cues on Baseline Gait in Early PD and Healthy Older Adults
The effects of auditory cues at baseline on participants with PD and healthy older adults are summarized in Table 2. There was a positive main effect of task reflected by an increase in step velocity (P < 0.001) and step length (P = 0.002) and a decrease in step time (P < 0.001). However, there was an increase in step length variability (P = 0.003) and step time variability (P = 0.005). No interactions between group and cue condition were observed. These results indicate that both participants with early PD and healthy older adults had a similar response to the auditory cue.
Effect of Auditory Cues in a Subset of Participants With PD After 3 Years—Effect of Disease Progression
After 3 years, the subset of participants with PD (n = 9) had worse MoCA scores (baseline: 28.78 ± 1.9; follow-up: 27.55 ± 2.6; P = 0.041), more severe motor deficits (MDS-UPDRS-III, baseline 26.22 ± 9.4; follow-up 33.4 ± 13.4; P = 0.013), poorer attention (increase in POA, baseline 1277.73 ± 151.2; follow-up 1419.7 ± 284.2; P = 0.008), and a significant increase in LEDD (baseline: 303.33 ± 92.2, follow-up: 505.22 ± 219.3; P = 0.012). At follow-up, participants with PD had significantly shorter step length (baseline 0.70 ± 0.07; follow-up 0.64 ± 0.10) and greater step time variability (baseline 10.25 ± 3.36; follow up 15.36 ± 5.77) compared with baseline (see Table 3). When comparing those who did (completers) and did not (noncompleters) return for the follow-up visit (Table 4), those who did not return had a poorer MoCA at baseline (completers: 28.77 ± 1.92, noncompleters: 26.25 ± 3.07, P = 0.044) and higher number of participants at H&Y stage 2 (completers: H&Y 1 = 2, H&Y 2 = 7; noncompleters: H&Y 1 = 0, H&Y 2 = 16, P = 0.049).
The individuals with PD who participated in the longitudinal study demonstrated no benefits of auditory cue at baseline as well as greater gait variability compared to as well as increased in gait variability in response to the cue. After 3 years, this subset demonstrated a positive effect of cue for step velocity (P = 0.015) and step length (P = 0.021) (Figure 2A). In addition, in contrast to the baseline test, there was no increase in step time variability with cueing (P = 0.859) (see Figure 2B; Table 5).
We aimed to understand the effect of auditory cues in people with newly diagnosed PD and how this compared with healthy older adults. Our results indicate that people with early PD benefitted from auditory cueing and this was in a similar manner to healthy older adults. Comparable to other work in early PD, our participants improved their cadence and velocity.24 These findings demonstrate that auditory cues provide an effective strategy to compensate for loss of basal ganglia output even in early disease.25 , 26 Despite the beneficial effects of cueing on step velocity, step length, and step time, these gait improvements came at the cost of increased variability of step time and step length. Interestingly, the same response was observed in healthy older adults. Previous studies have shown that auditory cues have a negative effect on gait variability in healthy individuals10 , 27 and this may be mirrored in the effect we observed in our early cohort. Although the increase in gait variability was only small in our cohort, these results may provide initial evidence that cues too early in disease may increase gait variability possibly due to dual-task burden, and this should be replicated in a larger cohort.
In a subset of participants, we aimed to understand how response to auditory cueing changes with disease progression and, to our knowledge, this is the first study to do so. Our results indicate that spatiotemporal characteristics responded positively to cues at a 3-year follow-up (ie, a more progressed state), but not at baseline. Therefore, our pilot work supports our hypothesis that auditory cueing may be more beneficial in later disease compared with early disease. Although exploratory, these findings provide preliminary evidence for value of using auditory cues for clinical practice as disease progresses in persons with PD.
As PD progressed, auditory cues in a subset of our participants showed improvements to spatial and temporal characteristics, but this was no longer at the cost of increased gait variability.28 , 29 This supports our hypothesis that perhaps the response to auditory cues may become more optimal as disease progresses. In our follow-up cohort, disease severity, gait, and attentional resources were shown to decline. These results may indicate that, with further basal ganglia dopamine loss and increased gait deficits, our participants had a better response to the auditory cues. In addition, loss of attentional resources may make people with PD more dependent on external cues, denoting a more optimal time point for the use of auditory cues within clinical intervention.
The cohort in this study presented at an earlier stage in comparison to previous work. Arias and Cudeiro30 demonstrated efficacy of auditory cues for reducing stride time variability of people with PD in H&Y stages 3 and 4. Also, our auditory cues were set to individual cadence, whereas previous work has set cues at a higher tempo. For example, Hausdorff et al10 found benefits of auditory cue on stride time variability when the cue was set at 110% of individual participants' cadence. However, the same was not found when the cue was set by participants' comfortable walking cadence. These findings suggest that disease stage and tempo of auditory cue should be considered when implementing auditory cues clinically, as they may affect the gait response to cue.
It is valuable to note that in our cohort there was variability in response to the auditory cue (as demonstrated in Figure 2). Our findings represent what is observed clinically as well as in previous cueing literature.5 Reasons for heterogeneity in response to cueing remain unknown and the underlying mechanisms are poorly understood, although theories suggest that attention may play a role. Therefore, variability in response to auditory cues may depend on cognitive capacity of individuals. Further work in larger cohorts and using different cue techniques is needed to further understand the heterogeneity of cue response.
Auditory Cueing in Late-Stage Disease
Our exploratory findings provide evidence for early PD only. In later disease because cognitive impairment increases,31 people with PD may no longer have the attentional resources to benefit from external cues. In later disease, it is unclear how higher levels of cognitive impairment influence response to an external cue. A small pilot study has demonstrated benefits of auditory cueing in mild cognitive impairment32; however, future research is required.
This pilot study has a number of limitations that need to be recognized. First, participants in the healthy group were not followed up over the 3 years. However, our main interest was the effect of disease progression to cue response. Second, the number of participants with PD in the follow-up assessment was small and a larger sample size will be necessary to confirm our findings. Third, it would have been interesting to explore the effect of auditory cues set at both individual's baseline cadence and above and below preferred cadence, as this has previously had a positive effect on gait in PD.23 , 33 In addition, our methodology of instructing participants to take a large step in time with the cue may have encouraged the use of attentional cue strategies. Further work should examine the effect of different types of cue strategies over disease progression. Finally, it will be important to address the heterogeneity of clinical presentation of PD, as we hypothesize that intervention cannot take a “one size fits all” approach.
Auditory cueing was associated with increased gait speed, step length, and step time in both participants with early PD and healthy older adults. In both groups, cueing was also associated with increased variability of step length and step time. In a small subset of participants with PD examined 3 years after the initial test, we identified an increase in response to auditory cues as disease progressed. Future work should focus on larger cohorts over a longer period to confirm these findings.
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gait; human movement system; rehabilitation; timing, variability
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