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Stepping reaction time and gait adaptability are significantly impaired in people with Parkinson's disease: Implications for fall risk
Parkinsonism and Related Disorders 47 (2018) 32e38
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Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Stepping reaction time and gait adaptability are significantly impaired in people with Parkinson's disease: Implications for fall risk Maria Joana D. Caetano a, b, *, Stephen R. Lord a, b, Natalie E. Allen c, Matthew A. Brodie a, Jooeun Song c, Serene S. Paul c, d, Colleen G. Canning c, Jasmine C. Menant a, b a
Neuroscience Research Australia, Sydney, Australia School of Public Health & Community Medicine, University of New South Wales, Sydney, Australia Faculty of Health Sciences, The University of Sydney, Sydney, Australia d Musculoskeletal Health Sydney, School of Public Health, The University of Sydney, Sydney, NSW, Australia b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 25 August 2017 Received in revised form 27 October 2017 Accepted 21 November 2017
Background: Decline in the ability to take effective steps and to adapt gait, particularly under challenging conditions, may be important reasons why people with Parkinson's disease (PD) have an increased risk of falling. This study aimed to determine the extent of stepping and gait adaptability impairments in PD individuals as well as their associations with PD symptoms, cognitive function and previous falls. Methods: Thirty-three older people with PD and 33 controls were assessed in choice stepping reaction time, Stroop stepping and gait adaptability tests; measurements identified as fall risk factors in older adults. Results: People with PD had similar mean choice stepping reaction times to healthy controls, but had significantly greater intra-individual variability. In the Stroop stepping test, the PD participants were more likely to make an error (48 vs 18%), took 715 ms longer to react (2312 vs 1517 ms) and had significantly greater response variability (536 vs 329 ms) than the healthy controls. People with PD also had more difficulties adapting their gait in response to targets (poorer stepping accuracy) and obstacles (increased number of steps) appearing at short notice on a walkway. Within the PD group, higher disease severity, reduced cognition and previous falls were associated with poorer stepping and gait adaptability performances. Conclusions: People with PD have reduced ability to adapt gait to unexpected targets and obstacles and exhibit poorer stepping responses, particularly in a test condition involving conflict resolution. Such impaired stepping responses in Parkinson's disease are associated with disease severity, cognitive impairment and falls. © 2017 Elsevier Ltd. All rights reserved.
Keywords: Parkinson's disease Choice stepping reaction time Stroop stepping test Gait adaptability Obstacle avoidance Accidental falls
1. Introduction Balance and gait impairments are disabling symptoms of Parkinson's disease (PD) that adversely affect performance of daily activities, reduce independence and increase the risk of falls. Around 60% of people with PD fall at least once a year, with a large proportion (50e86%) falling recurrently [1]. Most falls occur when people with PD are walking and when their symptoms are controlled i.e. in the “on medication” status [2]. To avoid falls while
* Corresponding author. Neuroscience Research Australia, Barker Street, Randwick, NSW 2031, Australia. E-mail address: [email protected] (M.J.D. Caetano). https://doi.org/10.1016/j.parkreldis.2017.11.340 1353-8020/© 2017 Elsevier Ltd. All rights reserved.
performing daily activities, effective stepping responses and gait adjustments, appropriately scaled for speed, magnitude, direction and accuracy, are required. Declines in the ability to adapt stepping and gait behavior, particularly under challenging conditions, might contribute to trips; which is frequently reported as a cause of falls in people with PD [3]. It has been proposed that attentional control deficits may lead to less effective behavioral responses in people with PD [4]. Several studies using finger-tapping tasks indicate people with PD, compared with controls, become increasingly slow to respond to a stimulus as choice complexity increases [5]; are slower to respond to a target flanked by incongruent distractors [6] and make more errors in the incongruent trials of the Stroop task [7]. Although deficits in finger-task reaction time are well
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documented and related to an increased risk of falling [8], little is known about the effects of attention control on stepping in people with PD - a task previously associated with an increased fall risk in older people with and without mild cognitive impairment [9e11]. This is of interest as the stepping tasks capture both cognitive and motor components of reaction time performance and thus may be useful tools for effective fall prevention for people with PD. Likewise, measurements of the ability to adapt gait, particularly in challenging environmental conditions, may also provide valuable information about impaired behavioural responses in PD, as attentional deficits are also related to gait impairments [12]. Previous research on attention control of stepping using a virtual reality paradigm has shown that people with PD with freezing of gait have longer motor pauses when required to respond to a conflicting stimulus (i.e. a red coloured stimulus to move the feet while seated) compared with people with PD without freezing of gait and non-PD controls [13]. PD patients with freezing of gait also display inappropriate postural adjustments prior to step initiation when required to respond to an attentional task (finger press in response to an auditory stimulus) [14]. Similarly, people with PD in their “off” medication state show a slower stepping reaction time than controls in a task requiring stepping forward or backward as soon as a coloured shape (i.e. cross or circle; yellow or blue) is presented on a screen, with PD freezers being more affected [15]. There is also evidence that the ability to adapt gait in response to upcoming environmental changes is impaired in PD. Previous studies using obstacle avoidance paradigms have shown that people with PD approach and step over a fixed obstacle slower and with smaller steps than control participants [16]. They also exhibit impaired foot clearance (shorter vertical foot-obstacle distance) during obstacle crossing [17] and impaired foot placement accuracy in a walking task involving fixed stepping targets [18]. Although these studies provide good insights into PD stepping and gait behaviour, no studies have investigated attention control of stepping in people with PD in their “on” medication state during tasks requiring stepping with both legs in multiple directions (forward, backward, right and left). Likewise, the ability to adapt gait in response to unexpected hazards appearing on the pathway [19] has not been investigated to date in PD. Such investigations could provide new insights for effective fall prevention for people with PD. Thus, the aims of this study were to determine a) the extent of stepping response and gait adaptability impairments in people with PD, and b) the clinical and cognitive correlates of such deficits within the PD group. We hypothesised that compared with healthy controls, people with PD would demonstrate impaired stepping and gait responses, and that such deficits would be associated with poorer cognitive function, worse PD symptoms and previous falls. 2. Methods The study was approved by the University of New South Wales and the Sydney University Human Research Ethics Committees. Participants provided written informed consent prior to participation. 2.1. Participants Participants were recruited from metropolitan Sydney, Australia through the research team's research volunteer databases and through Parkinson's NSW newsletters and support groups. PD volunteers were recruited for a training study (ACTRN12613000688785) and their data were collected as part of the baseline assessments. Participants were included if they were 65 years and older, living in the community, able to walk unaided
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for 30 m and cognitively capable of following all instructions (MOCA scores 20e30). Participants with PD were required to have been on the same PD medication for at least two weeks. Volunteers with and without PD were excluded if they had any medical conditions which would preclude or interfere with the physical assessment (e.g. physician diagnosed dementia, acute or terminal illness, progressive neurodegenerative diseases (other than PD), major psychiatric illnesses, colour-blindness or visual impairments that could not be corrected). Researchers experienced in working with people with PD and trained in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) administered section 3 of the scale (motor examination) [20], the Hoehn and Yahr rating scale (H&Y) [21] and The New Freezing of Gait Questionnaire [22] for the PD participants. Table 1 presents the demographic, anthropometric and cognitive (Montreal Cognitive Assessment (MoCA score [23])) data for both groups, as well as clinical characteristics for the PD participants. 2.2. Choice stepping reaction time (CSRT) and Stroop stepping tests Stepping performance was measured with the CSRT [10] and Stroop stepping [11] tests. A custom-made step mat with six target arrows (right, left, right front and back and left front and back) as well as two central stance panels to indicate the position to initiate steps and return to after completing them was used for both tests (Fig. 1eF1 and F2). Participants were instructed to stand on the central panels. For the CSRT test, the configuration of the step panels was presented on a screen in front of the participants and they were asked to make rapid step responses to the target arrows panels in response to corresponding visual stimuli presented randomly on the screen and return to the center panels. Six practice trials and 18 test trials were administered. CSRT performance was measured in milliseconds (ms) and subdivided into: 1) decision time (i.e. stimulus presentation to foot lift-off), 2) movement time (i.e. foot lift-off to step-down) and 3) total response time (i.e. sum of the decision time and movement time). The average time per trial
Table 1 Demographic, anthropometric and cognitive characteristics of Parkinson's disease and control groups, as well as clinical data specific to Parkinson's disease. Data presented are mean ± SD unless stated otherwise. Variables
Age (years) Number of women (%) Body mass (kg) Body height (cm) Usual gait velocity (m/s) Usual step length (m) MoCA (score)a Previous falls (# of participants (%))b MDS-UPDRS-III (score)c Hoehn and Yahr stage Years since diagnosis Freezing of gait (# of participants (%))d
Parkinson's disease
Control
n ¼ 33
n ¼ 33
70 ± 4 13 (39) 76.3 ± 13.8 170.7 ± 8.0 1.26 ± 0.24 0.67 ± 0.11z 26.3 ± 2.8 18 (54)* 36.1 ± 12.2 2.1 ± 0.4 7.8 ± 3.8 10 (30)
71 ± 4 19 (58) 75.8 ± 14.6 168.9 ± 10.4 1.29 ± 0.15 0.69 ± 0.07 27.2 ± 2.4 10 (30) n/a n/a n/a n/a
*Significantly different between control and Parkinson's disease groups (p < 0.05); ztrend (p ¼ 0.062). a Montreal Cognitive Assessment (adjusted for years of education), score range 0e30, high scores indicate better cognitive performance. b Number of participants who reported falling once or more in the previous 12 months. c Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale, section 3 (motor examination), score range 0e132, high scores indicate increased disease severity. d The New Freezing of Gait Questionnaire, number of participants that reported freezing of gait.
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Fig. 1. Stepping and gait adaptability tasks used in this study. (F1): Choice stepping reaction time (CSRT) test example screen. One of six arrows on the screen changes its color to green and the participant is asked to step as quickly as possible onto the same location of the pad (front left in this example). (F2): Stroop stepping test example screen. Participants step according to the word and not the arrow orientation. (F3): Overhead view of the gait adaptability experimental setup including obstacle avoidance (A), short target (B) and long target (C) conditions. Distance to the obstacle/target was personalized for each individual. The starting position (1) was adjusted to align the obstacle (3) with the fifth foot landing location based on the average foot placement from the baseline walking trials. The stepping targets were projected in two locations e 24.5 cm anterior (4) and 24.5 cm posterior (5) to the obstacle position (centre to centre distance), and thus required a short or a long step length respectively. The projection system for the three stimulus consisted of three torches installed in the ceiling and connected to a control box. A force sensitive resistor (Sparkfun SEN-09376) placed underneath the participant's right shoe and connected to a wireless transmitter attached to the participant's ankle triggered the light projection on the third heel strike following gait initiation (2). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
and the intra-individual variability (i.e. standard deviation over the total number of trials as calculated by Bunce et al. [9]) were calculated, as well as the number of participants who made at least one mistake (stepping on a different panel to that required). For the Stroop stepping test, an arrow was presented in the centre of the screen pointing in one of four directions (up, down, left and right) that matched the four possible step panel directions (forward, backward, left and right). A word indicating a different direction was written inside the arrow. Participants were instructed to ‘Step by the word’ as quickly as possible and therefore had to inhibit the response indicated by the arrow's orientation. A random sequence of 4 practice trials and 20 test trials in which the directions of word and orientation never matched was administered. The number of participants who made at least one mistake as well as the average total response time per trial time and the intra-
individual variability were measured.
2.3. Gait adaptability test (GAT) Participants were required to walk at their self-selected speed over an obstacle-free path (baseline condition). They were then instructed about the GAT. As described elsewhere [24], the GAT required participants to complete walking trials in four experimental conditions: (i) avoid stepping on a pink stimulus appearing two steps ahead (obstacle avoidance); (ii) stepping onto a green stimulus appearing slightly short of two steps ahead (short target); (iii) stepping onto a green stimulus appearing slightly further than two steps ahead (long target); (iv) walking with no stimulus appearing on the pathway (walk-through). Walk-through trials were included to encourage participants to walk naturally. Trials
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were presented in a randomized order for a total of three trials per condition. At least one practice trial per condition (baseline, walkthrough, obstacle avoidance, short target and long target) was performed until the task was understood, before data acquisition. The equipment and set-up have also been described in detail previously [24]. In brief, the targets and obstacle consisted of a coloured light stimulus projected onto an area on the walkway (21.5 21.5 cm for control group and 23 23 cm for PD group), presented on the third heel strike following gait initiation and appearing two steps ahead of the participant (Fig. 1-F3). The difference in size of the projected area between the groups of participants occurred due to differences in the ceiling height in which each light system was installed. Participants were instructed to step in the middle of the targets (green light) and to avoid stepping on the obstacle (pink light) but not step off the mat, and use any avoidance strategy. Participants were asked to start walking with the right foot in all conditions. Gait adaptability performance outcome measures were: (i) GAT errors - number of participants who made at least one mistake (stepping on an obstacle or missing a target); (ii) stepping accuracy for target conditions (distance between the centre of the target and the centre of the foot); (iii) number of steps taken to approach the target or obstacle (during interval between the appearance of the stimulus and the target or obstacle step); (iv) length of the two steps preceding the target or obstacle; and (v) velocity of the stride preceding the target or obstacle (averaged from successful trials). An electronic walkway (control group: 6 m-long GAITRite®mat,v4.0,2010CIR Systems, USA; PD group: 4 m-long ZenoMetrics®mat/PKMAS software,v2011-2013, Havertown, PA, USA) recorded the temporal and spatial gait parameters. Position coordinates of the foot with reference to the target or obstacle coordinates extracted from the electronic walkway were used to determine GAT variables using a Matlab routine (MathWorks, Natick, MA, USA).
2.4. Statistical analysis Differences in anthropometrics and cognitive measures between the PD and control groups were assessed using independent sample t-tests or Mann Whitney-U tests, as appropriate. The number of participants who made at least one error versus no errors for each test was compared between groups using Chi-square tests. Data normality and equality of variances were tested using the Skewness and Levene's tests, respectively. For variables with
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skewed distributions, data were log10 transformed. Betweengroups differences (PD versus controls) in the CSRT and Stroop stepping reaction times, and GAT measures were examined using General Linear Models (ANCOVA) controlling for age and height. Spearman's correlation analyses were used to examine the associations between CSRT, Stroop stepping and GAT measures and disease severity (score on UPDRS motor section), cognitive performance (MoCA score), freezing of gait and falling status (1 þ fall in past year) in the PD group. All significance levels were set at P < 0.05. Analyses were performed with SPSS (version 22 for Windows, IBM Corp.).
3. Results Thirty-three people with mild-moderate PD and 33 control participants performed the tests. Table 2 shows PD and control participants' stepping reaction time variables for the CSRT and Stroop stepping tasks. The number of participants who made at least one error in the CSRT task and the mean total response, decision and movement times were similar between people with PD and controls. However, the PD participants showed increased intraindividual variability in the CSRT task (total response and decision times) compared with controls. The PD participants also performed worse (increased number of participants who made at least one error, longer total response time and increased intra-individual variability) when responding to an incongruent stimulus in the Stroop stepping task. Table 3 shows PD and control participants' gait adaptability variables for each condition. Compared with controls, people with PD demonstrated poorer accuracy when stepping on targets and took multiple and shorter steps while approaching the obstacle. The strategies used by the participants consisted of a step over the obstacle or a step to the side. The percentage of participants who adopted a step-over strategy (control 24% vs PD 48%) or a side-step strategy (control 33% vs PD 21%) to negotiate the obstacle did not differ between groups (x2 ¼ 4.222; p ¼ 0.121). The remaining percentage of people (control 42% and PD 30%) alternated between the two strategies. Within the PD group, eight out of ten participants who made an error in the gait adaptability test also made an error in the stepping tests (seven participants in the Stroop stepping test and one participant in the CSRTtest). Within the PD group; higher UPDRS-III disease severity was associated with slower Stroop stepping total response times (r ¼ 0.596, p < 0.01) and increased number of obstacle approach
Table 2 Choice-stepping reaction time and Stroop stepping test variables for the Parkinson's disease and control groups. Data presented are mean ± SD unless stated otherwise. Variables
CSRT Errors (# of participants (%))a Decision time (ms) Movement time (ms) Total response time (ms) SST Errors (# of participants (%))a Total response time (ms)
Parkinson's disease
Control
n ¼ 33
n ¼ 33
Mean IIV Mean IIV Mean IIV
4 (12) 844 ± 166 156 ± 102** 303 ± 77 107 ± 67 1147 ± 213 193 ± 132**
1 (3) 838 ± 99 106 ± 51 328 ± 64 83 ± 42 1165 ± 151 120 ± 31
c2 ¼ 1.948 F(1,62) ¼ 0.001 F(1,62)¼8.579 F(1,62) ¼ 2.471 F(1,62) ¼ 2.967 F(1,62) ¼ 0.271 F(1,62)¼11.612
Mean IIV
16 (48)** 2312 ± 607** 536 ± 455*
6 (18) 1597 ± 303 329 ± 271
c2¼6.818 F(1,62)¼61.783 F(1,62)¼7.135
Notes: CSRT ¼ Choice Stepping Reaction Time test; SST ¼ Stroop Stepping Test; IIV ¼ intra-individual variability. Bold ¼ significant values (*p < 0.05; **p < 0.01). a Number of participants (%) who made at least one mistake in the stepping test.
Statistical tests
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Table 3 Gait adaptability test variables for the Parkinson's disease and control groups. Data presented are mean ± SD unless stated otherwise. GAT Variables
a
Errors (# of participants (%)) Target accuracy (cm)b Velocity (m/s) Step length (m)c Short target Long target Obstacle
Previous step Target step Previous step Target step Previous step Obstacle step
Number of stepsd Short target Long target Obstacle
Parkinson's disease
Control
Statistical tests
n ¼ 33
n ¼ 33
10 (30) 7.6 ± 2.6* 1.1 ± 0.3
6 (18) 5.9 ± 3.3 1.1 ± 0.2
c2 ¼ 1.320
0.55 ± 0.16 0.58 ± 0.13 0.56 ± 0.16 0.63 ± 0.16 0.54 ± 0.18* 0.71 ± 0.19
0.58 ± 0.13 0.57 ± 0.11 0.58 ± 0.11 0.67 ± 0.17 0.60 ± 0.10 0.70 ± 0.12
F(1,62) ¼ 1.210 F(1,62) ¼ 0.028 F(1,62) ¼ 1.055 F(1,62) ¼ 1.797 F(1,62)¼4.474 F(1,62) ¼ 0.000
2.2 ± 0.4 2.9 ± 0.7 2.8 ± 0.6*
2.1 ± 0.3 2.8 ± 0.5 2.6 ± 0.5
F(1,62) ¼ 0.430 F(1,62) ¼ 0.925 F(1,62)¼4.341
F(1,62)¼6.196 F(1,62) ¼ 0.870
Notes: GAT ¼ gait adaptability test. Bold ¼ significant values (*p < 0.05). a Number of participants (%) who made at least one mistake in the gait adaptability test. b Distance between the centre of the target and the centre of the foot; high values mean worse performance. c The step that hit or avoided the stimulus was named “target/obstacle step” and the preceding step was named “previous step. d number of steps taken to approach the target or obstacle (during interval between the appearance of the stimulus and the target or obstacle step).
steps in the GAT (r ¼ 0.401, p < 0.05; see Supplementary figure); poorer MoCA scores were significantly associated with slower CSRT decision times and Stroop stepping total response times (r ¼ 0.365, p < 0.05 and r ¼ 0.513, p < 0.01 respectively, see Supplementary figure), as well as with increased number of Stroop stepping errors (r ¼ 0.448,p < 0.01). Falling status (1 þ fall in past year) was significantly associated with slower CSRT (total response and decision times (r ¼ 0.364; r ¼ 0.384, p < 0.05 respectively)) and Stroop stepping total response times (r ¼ 0.375, p < 0.05). Finally, there was also a trend towards an association between freezing of gait and poorer target accuracy (r ¼ 0.325, p ¼ 0.065).
4. Discussion This study examined the effect of PD on stepping response and gait adaptability performances. Although people with PD had similar mean CSRT to healthy controls, they had significantly greater intra-individual CSRT variability. The addition of conflict resolution revealed more group differences. In the Stroop stepping test, the PD group were 30% more likely to make an error, took 715 ms longer to respond and had 207 ms greater intra-individual variability than controls. People with PD also had more difficulties adapting their gait in response to targets (i.e., poorer stepping accuracy) and obstacles (increased number of steps) appearing at short notice. The slower Stroop stepping response times exhibited by the PD participants may be attributed to motor related disease deficits (e.g. bradykinesia) [25] as suggested by a significant correlation between Stroop total response time and UPDRS-III severity. However, as the PD participants in this study had similar mean response times and number of errors to the healthy controls when responding to a congruent stimulus (CSRT task), the longer response times and increased number of errors exhibited in the incongruent trials (Stroop stepping test) cannot be attributed only to an effect of general slowing. Instead, it may reflect less effective behavioral responses in PD due to attentional control deficits [4] and/or impaired cognitive function as suggested by the significant correlations found between MoCA score and Stroop test performance. Results of electroencephalogram measurements also support
the hypothesis that people with PD have impaired inhibitory capacity during No-go trials when accompanied with normal Go trials [26]. In their study, Bokura et al. [26] found that compared with controls, people with PD had prolonged latency and lower amplitudes of event-related brain potential measures in a task requiring the suppression of a finger-tapping response. In addition, the No-go event-related brain potential measures were correlated with the number of commission errors and with test scores for frontal cognitive functions (modified Wisconsin Card Sorting, Verbal Fluency and Kana Pick-out Tests), indicating that inhibitory function deficits in PD may be related to impaired inhibitory executive function in the frontal lobe. It has also been suggested that problems with internal attentional control (internally driven decisions) in PD may lead to excessive reliance on external cues [27], which would explain the relatively preserved capacity to respond to a congruent stimulus (CSRT task). In the Stroop stepping test, responses were made by stepping to a left, right, forward or backward target and the dimension of the irrelevant stimulus presented was a left, right, forward or backward arrow. Thus this overlap between the irrelevant stimulus and the stepping response may have induced PD individuals to make an error and to take a slower and more variable stepping response. Several factors could have contributed to the increased intraindividual stepping reaction time variability displayed by the PD participants. As suggested for increased hand reaction time variability [28], it could reflect fluctuations in cognitive performance [29], particularly in already compromised attention and executive functions [4,28]. Alternatively, it may result from desynchronization of muscle activation [30] and/or variations in lower limb force generation [31] that are thought to lead to increased gait variability in people with PD [32]. There is also evidence that people with PD are more dependent on visual feedback to make accurate target steps [18]. Hence, when completing the GAT, the target appearance at short notice may have contributed to the poorer stepping accuracy of the PD participants. Limited executive function [4,28] and/or less effective balance control may also explain why the PD participants were less accurate in stepping on the targets in the GAT. Although small, the increased number of steps taken by the PD participants to approach the obstacle (mean difference of 0.2 steps
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representing a distance of approximately 10 cm) may be relevant to avoid tripping or falling while negotiating obstacles. This multiple step strategy may indicate difficulty in increasing step length to avoid the obstacle, as suggested by the shorter previous step length exhibited by the PD participants. Compared to the obstacle, the target conditions may have been less challenging for PD patients since they represent a visual cue for stepping. On the other hand, the obstacle condition required planning and execution of an avoidance strategy with changes in the linear progression of gait and/or base of support. Thus, the multiple step strategy may also indicate a behavioral strategy to compensate for motor related disease deficits [17] as suggested by the significant correlations between number of steps and UPDRS-III severity, and/or slowed cognitive processing [4,28] to solve the conflict resolution task (step or avoid the stimulus). Within the PD group poorer stepping performance was significantly associated with previous falls, suggesting that the inability to step quickly without making errors in complex environments is likely to increase the risk of falling during activities of daily living, particularly in challenging environmental conditions when encountering unexpected hazards. In fact, as found in older adults with mild cognitive impairment [9], the CSRT test might be more sensitive than traditional hand reaction time tasks in identifying those at increased risk of falls. We acknowledge the study has certain limitations. The sample sizes were relatively small and restricted to participants older than 65 years; also the gender makeup of the PD and control groups differed, albeit not significantly. Secondly, due to different test locations, both the targets and obstacles in the gait adaptability test were marginally larger for the PD group. However, we feel it is unlikely these small differences would have significantly influenced the findings reported here. In conclusion, we found that compared with their healthy peers, people with PD exhibited an impaired ability to adapt their stepping and walking behavior towards targets and obstacles. Our findings also provide further evidence of conflict resolution deficits associated with PD and complement research in finger-tapping responses by extending this work to stepping. Such impaired stepping responses seem to be linked to an increased risk of falling. This information may facilitate fall risk assessments and contribute to the development of new fall prevention strategies in people with PD. Future studies should investigate whether adaptive stepping and gait measures are associated with prospective falls, freezing of gait and conflict resolution neuropsychological performances in larger samples and whether rehabilitation interventions aimed at improving stepping and gait adaptability can reduce fall risk in people with PD. Funding This work was supported by the Conselho Nacional de Desen gico (CNPqe200748/2012-2) to volvimento Científico e Tecnolo M.J.D.C.; National Health and Medical Research Council to S.R.L.; Parkinson's New South Wales and The University of Canberra grant to N.E.A. Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.parkreldis.2017.11.340. References [1] N.E. Allen, A.K. Schwarzel, C.G. Canning, Recurrent falls in Parkinson's disease: a systematic review, Park. Dis. (2013) 906274, https://doi.org/10.1155/2013/
37
906274. [2] B.R. Bloem, Y.A.M. Grimbergen, M. Cramer, M. Willemsen, A.H. Zwinderman, Prospective assessment of falls in Parkinson's disease, J. Neurol. 248 (2001) 950e958, https://doi.org/10.1007/s004150170047. [3] T. Gazibara, T. Pekmezovic, D.K. Tepavcevic, et al., Circumstances of falls and fall-related injuries among patients with Parkinson's disease in an outpatient setting, Geriatr. Nurs. 35 (5) (2014) 364e369, https://doi.org/10.1016/ j.gerinurse.2014.05.001. [4] R. Cools, R. Rogers, R.A. Barker, T.W. Robbins, Top-down attentional control in Parkinson's disease: salient considerations, J. Cogn. Neurosci. 22 (5) (2010) 848e859, https://doi.org/10.1162/jocn.2009.21227. [5] J.A. Cooper, H.J. Sagar, P. Tidswell, N. Jordan, Slowed central processing in simple and go/no-go reaction time tasks in Parkinson's disease, Brain 117 (1994) 517e529, https://doi.org/10.1093/brain/117.3.517. [6] S.A. Wylie, W.P.M. van den Wildenberg, K.R. Ridderinkhof, et al., The effect of Parkinson's disease on interference control during action selection, Neuropsychologia 47 (1) (2009) 145e157, https://doi.org/10.1016/ j.neuropsychologia.2008.08.001. [7] J. Vandenbossche, N. Deroost, E. Soetens, et al., Conflict and freezing of gait in Parkinson's disease: support for a response control deficit, Neuroscience 206 (2012) 144e154, https://doi.org/10.1016/j.neuroscience.2011.12.048. [8] L.M. Allcock, E.N. Rowan, I.N. Steen, K. Wesnes, R.A. Kenny, D.J. Burn, Impaired attention predicts falling in Parkinson's disease, Park. Relat. Disord. 15 (2) (2009) 110e115, https://doi.org/10.1016/j.parkreldis.2008.03.010. [9] D. Bunce, B.I. Haynes, S.R. Lord, et al., Intraindividual stepping reaction time variability predicts falls in older adults with mild cognitive impairment, J. Gerontol. A Biol. Sci. Med. Sci. 72 (6) (2017) 832e837, https://doi.org/ 10.1093/gerona/glw164. [10] D. Schoene, S.R. Lord, P. Verhoef, S.T. Smith, A novel video gameebased device for measuring stepping performance and fall risk in older people, Arch. Phys. Med. Rehabil. 92 (6) (2011) 947e953, https://doi.org/10.1016/ j.apmr.2011.01.012. [11] D. Schoene, S.T. Smith, T.A. Davies, K. Delbaere, S.R. Lord, A Stroop Stepping Test (SST) using low-cost computer game technology discriminates between older fallers and non-fallers, Age Ageing 43 (2) (2014) 285e289, https:// doi.org/10.1093/ageing/aft157. [12] G. Yogev-Seligmann, J.M. Hausdorff, N. Giladi, The role of executive function and attention in gait, Mov. Disord. 23 (3) (2008) 329e342, https://doi.org/ 10.1002/mds.21720. [13] E. Matar, J.M. Shine, S.L. Naismith, S.J.G. Lewis, Using virtual reality to explore the role of conflict resolution and environmental salience in Freezing of Gait in Parkinson's disease, Park. Relat. Disord. 19 (11) (2013) 937e942, https:// doi.org/10.1016/j.parkreldis.2013.06.002. [14] C. Tard, K. Dujardin, J.L. Bourriez, et al., Attention modulates step initiation postural adjustments in Parkinson freezers, Park. Relat. Disord. 20 (3) (2014) 284e289, https://doi.org/10.1016/j.parkreldis.2013.11.016. [15] K. Smulders, R.A. Esselink, B.R. Bloem, R. Cools, Freezing of gait in Parkinson's disease is related to impaired motor switching during stepping, Mov. Disord. 30 (8) (2015) 1090e1097, https://doi.org/10.1002/mds.26133. [16] F. Pieruccini-Faria, R. Vitorio, Q.J. Almeida, et al., Evaluating the acute contributions of dopaminergic replacement to gait with obstacles in Parkinson's disease, J. Mot. Behav. 45 (5) (2013) 369e380, https://doi.org/10.1080/ 00222895.2013.810139. [17] R. Vitorio, E. Lirani-Silva, A.M. Baptista, et al., Disease severity affects obstacle crossing in people with Parkinson's disease, Gait Posture 40 (1) (2014) 266e269, https://doi.org/10.1016/j.gaitpost.2014.03.003. [18] R. Vitorio, L.T. Gobbi, E. Lirani-Silva, R. Moraes, Q.J. Almeida, Synchrony of gaze and stepping patterns in people with Parkinson's disease, Behav. Brain Res. 307 (2016) 159e164, https://doi.org/10.1016/j.bbr.2016.04.010. [19] M.J.D. Caetano, S.R. Lord, M.A. Brodie, et al., Executive functioning, concern about falling and quadriceps strength mediate the relationship between impaired gait adaptability and fall risk in older people, Gait Posture 59 (2018) 188e192, https://doi.org/10.1016/j.gaitpost.2017.10.017. [20] C.G. Goetz, G.T. Stebbins, B.C. Tilley, Calibration of unified Parkinson's disease rating scale scores to Movement Disorder Society-unified Parkinson's disease rating scale scores, Mov. Disord. 27 (10) (2012) 1239e1242, https://doi.org/ 10.1002/mds.25122. [21] M.M. Hoehn, M.D. Yahr, Parsinsonism: onset, progression and mortality, Neurology 17 (5) (1967) 427e442, 10.1212/WNL.17.5.427:1526-632X. [22] A. Nieuwboer, L. Rochester, T. Herman, et al., Reliability of the new freezing of gait questionnaire: agreement between patients with Parkinson's disease and their carers, Gait Posture 30 (4) (2009) 459e463, https://doi.org/10.1016/ j.gaitpost.2009.07.108. [23] Z.S. Nasreddine, N.A. Phillips, V. Bedirian, et al., The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment, J. Am. Geriatr. Soc. 53 (2005) 695e699, https://doi.org/10.1111/j.15325415.2005.53221.x. [24] M.J.D. Caetano, J.C. Menant, D. Schoene, P.H.S. Pelicioni, D.L. Sturnieks, S.R. Lord, Sensorimotor and cognitive predictors of impaired gait adaptability in older people, J. Gerontol. A Biol. Sci. Med. Sci. 72 (9) (2017) 1257e1263, https://doi.org/10.1093/gerona/glw171. [25] J. Jankovic, Parkinson's disease: clinical features and diagnosis, J. Neurol. Neurosurg. Psychiatry 79 (4) (2008) 368e376, https://doi.org/10.1136/ jnnp.2007.131045. [26] H. Bokura, S. Yamaguchi, S. Kobayashi, Event-related potentials for response
38
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inhibition in Parkinson's disease, Neuropsychologia 43 (6) (2005) 967e975, https://doi.org/10.1016/j.neuropsychologia.2004.08.010. [27] P. Praamstra, D.F. Stegeman, A.R. Cools, M.W. Horstink, Reliance on external cues for movement initiation in Parkinson's disease. Evidence from movement-related potentials, Brain 121 (1) (1998) 167e177, https://doi.org/ 10.1093/brain/121.1.167. [28] J.M. Hausdorff, G.M. Doniger, S. Springer, G. Yogev, E.S. Simon, N. Giladi, A common cognitive profile in elderly fallers and in patients with Parkinson's disease: the prominence of impaired executive function and attention, Exp. Aging Res. 32 (4) (2006) 411e429, https://doi.org/10.1080/ 03610730600875817. [29] D.F. Hultsch, S.W. MacDonald, R.A. Dixon, Variability in reaction time
performance of younger and older adults, J. Gerontol. B Psychol. Sci. Soc. Sci. 57 (2) (2002) P101eP115, https://doi.org/10.1093/geronb/57.2.P101. [30] R.A. Miller, M.H. Thaut, G.C. McIntosh, R.R. Rice, Components of EMG symmetry and variability in parkinsonian and healthy elderly gait, Electroencephalogr. Clin. Neurophysiol. 101 (1) (1996) 1e7, https://doi.org/10.1016/ 0013-4694(95)00209-X. [31] A. Burleigh-Jacobs, F.B. Horak, J.G. Nutt, J.A. Obeso, Step initiation in Parkinson's disease: influence of levodopa and external sensory triggers, Mov. Disord. 12 (2) (1997) 206e215, https://doi.org/10.1002/mds.870120211. [32] J.M. Hausdorff, J.D. Schaafsma, Y. Balash, et al., Impaired regulation of stride variability in Parkinson's disease subjects with freezing of gait, Exp. Brain Res. 149 (2) (2003) 187e194, https://doi.org/10.1007/s00221-002-1354-8.
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Stepping reaction time and gait adaptability are significantly impaired in people with Parkinson's disease: Implications for fall risk Maria Joana D. Caetano a, b, *, Stephen R. Lord a, b, Natalie E. Allen c, Matthew A. Brodie a, Jooeun Song c, Serene S. Paul c, d, Colleen G. Canning c, Jasmine C. Menant a, b a
Neuroscience Research Australia, Sydney, Australia School of Public Health & Community Medicine, University of New South Wales, Sydney, Australia Faculty of Health Sciences, The University of Sydney, Sydney, Australia d Musculoskeletal Health Sydney, School of Public Health, The University of Sydney, Sydney, NSW, Australia b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 25 August 2017 Received in revised form 27 October 2017 Accepted 21 November 2017
Background: Decline in the ability to take effective steps and to adapt gait, particularly under challenging conditions, may be important reasons why people with Parkinson's disease (PD) have an increased risk of falling. This study aimed to determine the extent of stepping and gait adaptability impairments in PD individuals as well as their associations with PD symptoms, cognitive function and previous falls. Methods: Thirty-three older people with PD and 33 controls were assessed in choice stepping reaction time, Stroop stepping and gait adaptability tests; measurements identified as fall risk factors in older adults. Results: People with PD had similar mean choice stepping reaction times to healthy controls, but had significantly greater intra-individual variability. In the Stroop stepping test, the PD participants were more likely to make an error (48 vs 18%), took 715 ms longer to react (2312 vs 1517 ms) and had significantly greater response variability (536 vs 329 ms) than the healthy controls. People with PD also had more difficulties adapting their gait in response to targets (poorer stepping accuracy) and obstacles (increased number of steps) appearing at short notice on a walkway. Within the PD group, higher disease severity, reduced cognition and previous falls were associated with poorer stepping and gait adaptability performances. Conclusions: People with PD have reduced ability to adapt gait to unexpected targets and obstacles and exhibit poorer stepping responses, particularly in a test condition involving conflict resolution. Such impaired stepping responses in Parkinson's disease are associated with disease severity, cognitive impairment and falls. © 2017 Elsevier Ltd. All rights reserved.
Keywords: Parkinson's disease Choice stepping reaction time Stroop stepping test Gait adaptability Obstacle avoidance Accidental falls
1. Introduction Balance and gait impairments are disabling symptoms of Parkinson's disease (PD) that adversely affect performance of daily activities, reduce independence and increase the risk of falls. Around 60% of people with PD fall at least once a year, with a large proportion (50e86%) falling recurrently [1]. Most falls occur when people with PD are walking and when their symptoms are controlled i.e. in the “on medication” status [2]. To avoid falls while
* Corresponding author. Neuroscience Research Australia, Barker Street, Randwick, NSW 2031, Australia. E-mail address: [email protected] (M.J.D. Caetano). https://doi.org/10.1016/j.parkreldis.2017.11.340 1353-8020/© 2017 Elsevier Ltd. All rights reserved.
performing daily activities, effective stepping responses and gait adjustments, appropriately scaled for speed, magnitude, direction and accuracy, are required. Declines in the ability to adapt stepping and gait behavior, particularly under challenging conditions, might contribute to trips; which is frequently reported as a cause of falls in people with PD [3]. It has been proposed that attentional control deficits may lead to less effective behavioral responses in people with PD [4]. Several studies using finger-tapping tasks indicate people with PD, compared with controls, become increasingly slow to respond to a stimulus as choice complexity increases [5]; are slower to respond to a target flanked by incongruent distractors [6] and make more errors in the incongruent trials of the Stroop task [7]. Although deficits in finger-task reaction time are well
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documented and related to an increased risk of falling [8], little is known about the effects of attention control on stepping in people with PD - a task previously associated with an increased fall risk in older people with and without mild cognitive impairment [9e11]. This is of interest as the stepping tasks capture both cognitive and motor components of reaction time performance and thus may be useful tools for effective fall prevention for people with PD. Likewise, measurements of the ability to adapt gait, particularly in challenging environmental conditions, may also provide valuable information about impaired behavioural responses in PD, as attentional deficits are also related to gait impairments [12]. Previous research on attention control of stepping using a virtual reality paradigm has shown that people with PD with freezing of gait have longer motor pauses when required to respond to a conflicting stimulus (i.e. a red coloured stimulus to move the feet while seated) compared with people with PD without freezing of gait and non-PD controls [13]. PD patients with freezing of gait also display inappropriate postural adjustments prior to step initiation when required to respond to an attentional task (finger press in response to an auditory stimulus) [14]. Similarly, people with PD in their “off” medication state show a slower stepping reaction time than controls in a task requiring stepping forward or backward as soon as a coloured shape (i.e. cross or circle; yellow or blue) is presented on a screen, with PD freezers being more affected [15]. There is also evidence that the ability to adapt gait in response to upcoming environmental changes is impaired in PD. Previous studies using obstacle avoidance paradigms have shown that people with PD approach and step over a fixed obstacle slower and with smaller steps than control participants [16]. They also exhibit impaired foot clearance (shorter vertical foot-obstacle distance) during obstacle crossing [17] and impaired foot placement accuracy in a walking task involving fixed stepping targets [18]. Although these studies provide good insights into PD stepping and gait behaviour, no studies have investigated attention control of stepping in people with PD in their “on” medication state during tasks requiring stepping with both legs in multiple directions (forward, backward, right and left). Likewise, the ability to adapt gait in response to unexpected hazards appearing on the pathway [19] has not been investigated to date in PD. Such investigations could provide new insights for effective fall prevention for people with PD. Thus, the aims of this study were to determine a) the extent of stepping response and gait adaptability impairments in people with PD, and b) the clinical and cognitive correlates of such deficits within the PD group. We hypothesised that compared with healthy controls, people with PD would demonstrate impaired stepping and gait responses, and that such deficits would be associated with poorer cognitive function, worse PD symptoms and previous falls. 2. Methods The study was approved by the University of New South Wales and the Sydney University Human Research Ethics Committees. Participants provided written informed consent prior to participation. 2.1. Participants Participants were recruited from metropolitan Sydney, Australia through the research team's research volunteer databases and through Parkinson's NSW newsletters and support groups. PD volunteers were recruited for a training study (ACTRN12613000688785) and their data were collected as part of the baseline assessments. Participants were included if they were 65 years and older, living in the community, able to walk unaided
33
for 30 m and cognitively capable of following all instructions (MOCA scores 20e30). Participants with PD were required to have been on the same PD medication for at least two weeks. Volunteers with and without PD were excluded if they had any medical conditions which would preclude or interfere with the physical assessment (e.g. physician diagnosed dementia, acute or terminal illness, progressive neurodegenerative diseases (other than PD), major psychiatric illnesses, colour-blindness or visual impairments that could not be corrected). Researchers experienced in working with people with PD and trained in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) administered section 3 of the scale (motor examination) [20], the Hoehn and Yahr rating scale (H&Y) [21] and The New Freezing of Gait Questionnaire [22] for the PD participants. Table 1 presents the demographic, anthropometric and cognitive (Montreal Cognitive Assessment (MoCA score [23])) data for both groups, as well as clinical characteristics for the PD participants. 2.2. Choice stepping reaction time (CSRT) and Stroop stepping tests Stepping performance was measured with the CSRT [10] and Stroop stepping [11] tests. A custom-made step mat with six target arrows (right, left, right front and back and left front and back) as well as two central stance panels to indicate the position to initiate steps and return to after completing them was used for both tests (Fig. 1eF1 and F2). Participants were instructed to stand on the central panels. For the CSRT test, the configuration of the step panels was presented on a screen in front of the participants and they were asked to make rapid step responses to the target arrows panels in response to corresponding visual stimuli presented randomly on the screen and return to the center panels. Six practice trials and 18 test trials were administered. CSRT performance was measured in milliseconds (ms) and subdivided into: 1) decision time (i.e. stimulus presentation to foot lift-off), 2) movement time (i.e. foot lift-off to step-down) and 3) total response time (i.e. sum of the decision time and movement time). The average time per trial
Table 1 Demographic, anthropometric and cognitive characteristics of Parkinson's disease and control groups, as well as clinical data specific to Parkinson's disease. Data presented are mean ± SD unless stated otherwise. Variables
Age (years) Number of women (%) Body mass (kg) Body height (cm) Usual gait velocity (m/s) Usual step length (m) MoCA (score)a Previous falls (# of participants (%))b MDS-UPDRS-III (score)c Hoehn and Yahr stage Years since diagnosis Freezing of gait (# of participants (%))d
Parkinson's disease
Control
n ¼ 33
n ¼ 33
70 ± 4 13 (39) 76.3 ± 13.8 170.7 ± 8.0 1.26 ± 0.24 0.67 ± 0.11z 26.3 ± 2.8 18 (54)* 36.1 ± 12.2 2.1 ± 0.4 7.8 ± 3.8 10 (30)
71 ± 4 19 (58) 75.8 ± 14.6 168.9 ± 10.4 1.29 ± 0.15 0.69 ± 0.07 27.2 ± 2.4 10 (30) n/a n/a n/a n/a
*Significantly different between control and Parkinson's disease groups (p < 0.05); ztrend (p ¼ 0.062). a Montreal Cognitive Assessment (adjusted for years of education), score range 0e30, high scores indicate better cognitive performance. b Number of participants who reported falling once or more in the previous 12 months. c Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale, section 3 (motor examination), score range 0e132, high scores indicate increased disease severity. d The New Freezing of Gait Questionnaire, number of participants that reported freezing of gait.
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Fig. 1. Stepping and gait adaptability tasks used in this study. (F1): Choice stepping reaction time (CSRT) test example screen. One of six arrows on the screen changes its color to green and the participant is asked to step as quickly as possible onto the same location of the pad (front left in this example). (F2): Stroop stepping test example screen. Participants step according to the word and not the arrow orientation. (F3): Overhead view of the gait adaptability experimental setup including obstacle avoidance (A), short target (B) and long target (C) conditions. Distance to the obstacle/target was personalized for each individual. The starting position (1) was adjusted to align the obstacle (3) with the fifth foot landing location based on the average foot placement from the baseline walking trials. The stepping targets were projected in two locations e 24.5 cm anterior (4) and 24.5 cm posterior (5) to the obstacle position (centre to centre distance), and thus required a short or a long step length respectively. The projection system for the three stimulus consisted of three torches installed in the ceiling and connected to a control box. A force sensitive resistor (Sparkfun SEN-09376) placed underneath the participant's right shoe and connected to a wireless transmitter attached to the participant's ankle triggered the light projection on the third heel strike following gait initiation (2). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
and the intra-individual variability (i.e. standard deviation over the total number of trials as calculated by Bunce et al. [9]) were calculated, as well as the number of participants who made at least one mistake (stepping on a different panel to that required). For the Stroop stepping test, an arrow was presented in the centre of the screen pointing in one of four directions (up, down, left and right) that matched the four possible step panel directions (forward, backward, left and right). A word indicating a different direction was written inside the arrow. Participants were instructed to ‘Step by the word’ as quickly as possible and therefore had to inhibit the response indicated by the arrow's orientation. A random sequence of 4 practice trials and 20 test trials in which the directions of word and orientation never matched was administered. The number of participants who made at least one mistake as well as the average total response time per trial time and the intra-
individual variability were measured.
2.3. Gait adaptability test (GAT) Participants were required to walk at their self-selected speed over an obstacle-free path (baseline condition). They were then instructed about the GAT. As described elsewhere [24], the GAT required participants to complete walking trials in four experimental conditions: (i) avoid stepping on a pink stimulus appearing two steps ahead (obstacle avoidance); (ii) stepping onto a green stimulus appearing slightly short of two steps ahead (short target); (iii) stepping onto a green stimulus appearing slightly further than two steps ahead (long target); (iv) walking with no stimulus appearing on the pathway (walk-through). Walk-through trials were included to encourage participants to walk naturally. Trials
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were presented in a randomized order for a total of three trials per condition. At least one practice trial per condition (baseline, walkthrough, obstacle avoidance, short target and long target) was performed until the task was understood, before data acquisition. The equipment and set-up have also been described in detail previously [24]. In brief, the targets and obstacle consisted of a coloured light stimulus projected onto an area on the walkway (21.5 21.5 cm for control group and 23 23 cm for PD group), presented on the third heel strike following gait initiation and appearing two steps ahead of the participant (Fig. 1-F3). The difference in size of the projected area between the groups of participants occurred due to differences in the ceiling height in which each light system was installed. Participants were instructed to step in the middle of the targets (green light) and to avoid stepping on the obstacle (pink light) but not step off the mat, and use any avoidance strategy. Participants were asked to start walking with the right foot in all conditions. Gait adaptability performance outcome measures were: (i) GAT errors - number of participants who made at least one mistake (stepping on an obstacle or missing a target); (ii) stepping accuracy for target conditions (distance between the centre of the target and the centre of the foot); (iii) number of steps taken to approach the target or obstacle (during interval between the appearance of the stimulus and the target or obstacle step); (iv) length of the two steps preceding the target or obstacle; and (v) velocity of the stride preceding the target or obstacle (averaged from successful trials). An electronic walkway (control group: 6 m-long GAITRite®mat,v4.0,2010CIR Systems, USA; PD group: 4 m-long ZenoMetrics®mat/PKMAS software,v2011-2013, Havertown, PA, USA) recorded the temporal and spatial gait parameters. Position coordinates of the foot with reference to the target or obstacle coordinates extracted from the electronic walkway were used to determine GAT variables using a Matlab routine (MathWorks, Natick, MA, USA).
2.4. Statistical analysis Differences in anthropometrics and cognitive measures between the PD and control groups were assessed using independent sample t-tests or Mann Whitney-U tests, as appropriate. The number of participants who made at least one error versus no errors for each test was compared between groups using Chi-square tests. Data normality and equality of variances were tested using the Skewness and Levene's tests, respectively. For variables with
35
skewed distributions, data were log10 transformed. Betweengroups differences (PD versus controls) in the CSRT and Stroop stepping reaction times, and GAT measures were examined using General Linear Models (ANCOVA) controlling for age and height. Spearman's correlation analyses were used to examine the associations between CSRT, Stroop stepping and GAT measures and disease severity (score on UPDRS motor section), cognitive performance (MoCA score), freezing of gait and falling status (1 þ fall in past year) in the PD group. All significance levels were set at P < 0.05. Analyses were performed with SPSS (version 22 for Windows, IBM Corp.).
3. Results Thirty-three people with mild-moderate PD and 33 control participants performed the tests. Table 2 shows PD and control participants' stepping reaction time variables for the CSRT and Stroop stepping tasks. The number of participants who made at least one error in the CSRT task and the mean total response, decision and movement times were similar between people with PD and controls. However, the PD participants showed increased intraindividual variability in the CSRT task (total response and decision times) compared with controls. The PD participants also performed worse (increased number of participants who made at least one error, longer total response time and increased intra-individual variability) when responding to an incongruent stimulus in the Stroop stepping task. Table 3 shows PD and control participants' gait adaptability variables for each condition. Compared with controls, people with PD demonstrated poorer accuracy when stepping on targets and took multiple and shorter steps while approaching the obstacle. The strategies used by the participants consisted of a step over the obstacle or a step to the side. The percentage of participants who adopted a step-over strategy (control 24% vs PD 48%) or a side-step strategy (control 33% vs PD 21%) to negotiate the obstacle did not differ between groups (x2 ¼ 4.222; p ¼ 0.121). The remaining percentage of people (control 42% and PD 30%) alternated between the two strategies. Within the PD group, eight out of ten participants who made an error in the gait adaptability test also made an error in the stepping tests (seven participants in the Stroop stepping test and one participant in the CSRTtest). Within the PD group; higher UPDRS-III disease severity was associated with slower Stroop stepping total response times (r ¼ 0.596, p < 0.01) and increased number of obstacle approach
Table 2 Choice-stepping reaction time and Stroop stepping test variables for the Parkinson's disease and control groups. Data presented are mean ± SD unless stated otherwise. Variables
CSRT Errors (# of participants (%))a Decision time (ms) Movement time (ms) Total response time (ms) SST Errors (# of participants (%))a Total response time (ms)
Parkinson's disease
Control
n ¼ 33
n ¼ 33
Mean IIV Mean IIV Mean IIV
4 (12) 844 ± 166 156 ± 102** 303 ± 77 107 ± 67 1147 ± 213 193 ± 132**
1 (3) 838 ± 99 106 ± 51 328 ± 64 83 ± 42 1165 ± 151 120 ± 31
c2 ¼ 1.948 F(1,62) ¼ 0.001 F(1,62)¼8.579 F(1,62) ¼ 2.471 F(1,62) ¼ 2.967 F(1,62) ¼ 0.271 F(1,62)¼11.612
Mean IIV
16 (48)** 2312 ± 607** 536 ± 455*
6 (18) 1597 ± 303 329 ± 271
c2¼6.818 F(1,62)¼61.783 F(1,62)¼7.135
Notes: CSRT ¼ Choice Stepping Reaction Time test; SST ¼ Stroop Stepping Test; IIV ¼ intra-individual variability. Bold ¼ significant values (*p < 0.05; **p < 0.01). a Number of participants (%) who made at least one mistake in the stepping test.
Statistical tests
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Table 3 Gait adaptability test variables for the Parkinson's disease and control groups. Data presented are mean ± SD unless stated otherwise. GAT Variables
a
Errors (# of participants (%)) Target accuracy (cm)b Velocity (m/s) Step length (m)c Short target Long target Obstacle
Previous step Target step Previous step Target step Previous step Obstacle step
Number of stepsd Short target Long target Obstacle
Parkinson's disease
Control
Statistical tests
n ¼ 33
n ¼ 33
10 (30) 7.6 ± 2.6* 1.1 ± 0.3
6 (18) 5.9 ± 3.3 1.1 ± 0.2
c2 ¼ 1.320
0.55 ± 0.16 0.58 ± 0.13 0.56 ± 0.16 0.63 ± 0.16 0.54 ± 0.18* 0.71 ± 0.19
0.58 ± 0.13 0.57 ± 0.11 0.58 ± 0.11 0.67 ± 0.17 0.60 ± 0.10 0.70 ± 0.12
F(1,62) ¼ 1.210 F(1,62) ¼ 0.028 F(1,62) ¼ 1.055 F(1,62) ¼ 1.797 F(1,62)¼4.474 F(1,62) ¼ 0.000
2.2 ± 0.4 2.9 ± 0.7 2.8 ± 0.6*
2.1 ± 0.3 2.8 ± 0.5 2.6 ± 0.5
F(1,62) ¼ 0.430 F(1,62) ¼ 0.925 F(1,62)¼4.341
F(1,62)¼6.196 F(1,62) ¼ 0.870
Notes: GAT ¼ gait adaptability test. Bold ¼ significant values (*p < 0.05). a Number of participants (%) who made at least one mistake in the gait adaptability test. b Distance between the centre of the target and the centre of the foot; high values mean worse performance. c The step that hit or avoided the stimulus was named “target/obstacle step” and the preceding step was named “previous step. d number of steps taken to approach the target or obstacle (during interval between the appearance of the stimulus and the target or obstacle step).
steps in the GAT (r ¼ 0.401, p < 0.05; see Supplementary figure); poorer MoCA scores were significantly associated with slower CSRT decision times and Stroop stepping total response times (r ¼ 0.365, p < 0.05 and r ¼ 0.513, p < 0.01 respectively, see Supplementary figure), as well as with increased number of Stroop stepping errors (r ¼ 0.448,p < 0.01). Falling status (1 þ fall in past year) was significantly associated with slower CSRT (total response and decision times (r ¼ 0.364; r ¼ 0.384, p < 0.05 respectively)) and Stroop stepping total response times (r ¼ 0.375, p < 0.05). Finally, there was also a trend towards an association between freezing of gait and poorer target accuracy (r ¼ 0.325, p ¼ 0.065).
4. Discussion This study examined the effect of PD on stepping response and gait adaptability performances. Although people with PD had similar mean CSRT to healthy controls, they had significantly greater intra-individual CSRT variability. The addition of conflict resolution revealed more group differences. In the Stroop stepping test, the PD group were 30% more likely to make an error, took 715 ms longer to respond and had 207 ms greater intra-individual variability than controls. People with PD also had more difficulties adapting their gait in response to targets (i.e., poorer stepping accuracy) and obstacles (increased number of steps) appearing at short notice. The slower Stroop stepping response times exhibited by the PD participants may be attributed to motor related disease deficits (e.g. bradykinesia) [25] as suggested by a significant correlation between Stroop total response time and UPDRS-III severity. However, as the PD participants in this study had similar mean response times and number of errors to the healthy controls when responding to a congruent stimulus (CSRT task), the longer response times and increased number of errors exhibited in the incongruent trials (Stroop stepping test) cannot be attributed only to an effect of general slowing. Instead, it may reflect less effective behavioral responses in PD due to attentional control deficits [4] and/or impaired cognitive function as suggested by the significant correlations found between MoCA score and Stroop test performance. Results of electroencephalogram measurements also support
the hypothesis that people with PD have impaired inhibitory capacity during No-go trials when accompanied with normal Go trials [26]. In their study, Bokura et al. [26] found that compared with controls, people with PD had prolonged latency and lower amplitudes of event-related brain potential measures in a task requiring the suppression of a finger-tapping response. In addition, the No-go event-related brain potential measures were correlated with the number of commission errors and with test scores for frontal cognitive functions (modified Wisconsin Card Sorting, Verbal Fluency and Kana Pick-out Tests), indicating that inhibitory function deficits in PD may be related to impaired inhibitory executive function in the frontal lobe. It has also been suggested that problems with internal attentional control (internally driven decisions) in PD may lead to excessive reliance on external cues [27], which would explain the relatively preserved capacity to respond to a congruent stimulus (CSRT task). In the Stroop stepping test, responses were made by stepping to a left, right, forward or backward target and the dimension of the irrelevant stimulus presented was a left, right, forward or backward arrow. Thus this overlap between the irrelevant stimulus and the stepping response may have induced PD individuals to make an error and to take a slower and more variable stepping response. Several factors could have contributed to the increased intraindividual stepping reaction time variability displayed by the PD participants. As suggested for increased hand reaction time variability [28], it could reflect fluctuations in cognitive performance [29], particularly in already compromised attention and executive functions [4,28]. Alternatively, it may result from desynchronization of muscle activation [30] and/or variations in lower limb force generation [31] that are thought to lead to increased gait variability in people with PD [32]. There is also evidence that people with PD are more dependent on visual feedback to make accurate target steps [18]. Hence, when completing the GAT, the target appearance at short notice may have contributed to the poorer stepping accuracy of the PD participants. Limited executive function [4,28] and/or less effective balance control may also explain why the PD participants were less accurate in stepping on the targets in the GAT. Although small, the increased number of steps taken by the PD participants to approach the obstacle (mean difference of 0.2 steps
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representing a distance of approximately 10 cm) may be relevant to avoid tripping or falling while negotiating obstacles. This multiple step strategy may indicate difficulty in increasing step length to avoid the obstacle, as suggested by the shorter previous step length exhibited by the PD participants. Compared to the obstacle, the target conditions may have been less challenging for PD patients since they represent a visual cue for stepping. On the other hand, the obstacle condition required planning and execution of an avoidance strategy with changes in the linear progression of gait and/or base of support. Thus, the multiple step strategy may also indicate a behavioral strategy to compensate for motor related disease deficits [17] as suggested by the significant correlations between number of steps and UPDRS-III severity, and/or slowed cognitive processing [4,28] to solve the conflict resolution task (step or avoid the stimulus). Within the PD group poorer stepping performance was significantly associated with previous falls, suggesting that the inability to step quickly without making errors in complex environments is likely to increase the risk of falling during activities of daily living, particularly in challenging environmental conditions when encountering unexpected hazards. In fact, as found in older adults with mild cognitive impairment [9], the CSRT test might be more sensitive than traditional hand reaction time tasks in identifying those at increased risk of falls. We acknowledge the study has certain limitations. The sample sizes were relatively small and restricted to participants older than 65 years; also the gender makeup of the PD and control groups differed, albeit not significantly. Secondly, due to different test locations, both the targets and obstacles in the gait adaptability test were marginally larger for the PD group. However, we feel it is unlikely these small differences would have significantly influenced the findings reported here. In conclusion, we found that compared with their healthy peers, people with PD exhibited an impaired ability to adapt their stepping and walking behavior towards targets and obstacles. Our findings also provide further evidence of conflict resolution deficits associated with PD and complement research in finger-tapping responses by extending this work to stepping. Such impaired stepping responses seem to be linked to an increased risk of falling. This information may facilitate fall risk assessments and contribute to the development of new fall prevention strategies in people with PD. Future studies should investigate whether adaptive stepping and gait measures are associated with prospective falls, freezing of gait and conflict resolution neuropsychological performances in larger samples and whether rehabilitation interventions aimed at improving stepping and gait adaptability can reduce fall risk in people with PD. Funding This work was supported by the Conselho Nacional de Desen gico (CNPqe200748/2012-2) to volvimento Científico e Tecnolo M.J.D.C.; National Health and Medical Research Council to S.R.L.; Parkinson's New South Wales and The University of Canberra grant to N.E.A. Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.parkreldis.2017.11.340. References [1] N.E. Allen, A.K. Schwarzel, C.G. Canning, Recurrent falls in Parkinson's disease: a systematic review, Park. Dis. (2013) 906274, https://doi.org/10.1155/2013/
37
906274. [2] B.R. Bloem, Y.A.M. Grimbergen, M. Cramer, M. Willemsen, A.H. Zwinderman, Prospective assessment of falls in Parkinson's disease, J. Neurol. 248 (2001) 950e958, https://doi.org/10.1007/s004150170047. [3] T. Gazibara, T. Pekmezovic, D.K. Tepavcevic, et al., Circumstances of falls and fall-related injuries among patients with Parkinson's disease in an outpatient setting, Geriatr. Nurs. 35 (5) (2014) 364e369, https://doi.org/10.1016/ j.gerinurse.2014.05.001. [4] R. Cools, R. Rogers, R.A. Barker, T.W. Robbins, Top-down attentional control in Parkinson's disease: salient considerations, J. Cogn. Neurosci. 22 (5) (2010) 848e859, https://doi.org/10.1162/jocn.2009.21227. [5] J.A. Cooper, H.J. Sagar, P. Tidswell, N. Jordan, Slowed central processing in simple and go/no-go reaction time tasks in Parkinson's disease, Brain 117 (1994) 517e529, https://doi.org/10.1093/brain/117.3.517. [6] S.A. Wylie, W.P.M. van den Wildenberg, K.R. Ridderinkhof, et al., The effect of Parkinson's disease on interference control during action selection, Neuropsychologia 47 (1) (2009) 145e157, https://doi.org/10.1016/ j.neuropsychologia.2008.08.001. [7] J. Vandenbossche, N. Deroost, E. Soetens, et al., Conflict and freezing of gait in Parkinson's disease: support for a response control deficit, Neuroscience 206 (2012) 144e154, https://doi.org/10.1016/j.neuroscience.2011.12.048. [8] L.M. Allcock, E.N. Rowan, I.N. Steen, K. Wesnes, R.A. Kenny, D.J. Burn, Impaired attention predicts falling in Parkinson's disease, Park. Relat. Disord. 15 (2) (2009) 110e115, https://doi.org/10.1016/j.parkreldis.2008.03.010. [9] D. Bunce, B.I. Haynes, S.R. Lord, et al., Intraindividual stepping reaction time variability predicts falls in older adults with mild cognitive impairment, J. Gerontol. A Biol. Sci. Med. Sci. 72 (6) (2017) 832e837, https://doi.org/ 10.1093/gerona/glw164. [10] D. Schoene, S.R. Lord, P. Verhoef, S.T. Smith, A novel video gameebased device for measuring stepping performance and fall risk in older people, Arch. Phys. Med. Rehabil. 92 (6) (2011) 947e953, https://doi.org/10.1016/ j.apmr.2011.01.012. [11] D. Schoene, S.T. Smith, T.A. Davies, K. Delbaere, S.R. Lord, A Stroop Stepping Test (SST) using low-cost computer game technology discriminates between older fallers and non-fallers, Age Ageing 43 (2) (2014) 285e289, https:// doi.org/10.1093/ageing/aft157. [12] G. Yogev-Seligmann, J.M. Hausdorff, N. Giladi, The role of executive function and attention in gait, Mov. Disord. 23 (3) (2008) 329e342, https://doi.org/ 10.1002/mds.21720. [13] E. Matar, J.M. Shine, S.L. Naismith, S.J.G. Lewis, Using virtual reality to explore the role of conflict resolution and environmental salience in Freezing of Gait in Parkinson's disease, Park. Relat. Disord. 19 (11) (2013) 937e942, https:// doi.org/10.1016/j.parkreldis.2013.06.002. [14] C. Tard, K. Dujardin, J.L. Bourriez, et al., Attention modulates step initiation postural adjustments in Parkinson freezers, Park. Relat. Disord. 20 (3) (2014) 284e289, https://doi.org/10.1016/j.parkreldis.2013.11.016. [15] K. Smulders, R.A. Esselink, B.R. Bloem, R. Cools, Freezing of gait in Parkinson's disease is related to impaired motor switching during stepping, Mov. Disord. 30 (8) (2015) 1090e1097, https://doi.org/10.1002/mds.26133. [16] F. Pieruccini-Faria, R. Vitorio, Q.J. Almeida, et al., Evaluating the acute contributions of dopaminergic replacement to gait with obstacles in Parkinson's disease, J. Mot. Behav. 45 (5) (2013) 369e380, https://doi.org/10.1080/ 00222895.2013.810139. [17] R. Vitorio, E. Lirani-Silva, A.M. Baptista, et al., Disease severity affects obstacle crossing in people with Parkinson's disease, Gait Posture 40 (1) (2014) 266e269, https://doi.org/10.1016/j.gaitpost.2014.03.003. [18] R. Vitorio, L.T. Gobbi, E. Lirani-Silva, R. Moraes, Q.J. Almeida, Synchrony of gaze and stepping patterns in people with Parkinson's disease, Behav. Brain Res. 307 (2016) 159e164, https://doi.org/10.1016/j.bbr.2016.04.010. [19] M.J.D. Caetano, S.R. Lord, M.A. Brodie, et al., Executive functioning, concern about falling and quadriceps strength mediate the relationship between impaired gait adaptability and fall risk in older people, Gait Posture 59 (2018) 188e192, https://doi.org/10.1016/j.gaitpost.2017.10.017. [20] C.G. Goetz, G.T. Stebbins, B.C. Tilley, Calibration of unified Parkinson's disease rating scale scores to Movement Disorder Society-unified Parkinson's disease rating scale scores, Mov. Disord. 27 (10) (2012) 1239e1242, https://doi.org/ 10.1002/mds.25122. [21] M.M. Hoehn, M.D. Yahr, Parsinsonism: onset, progression and mortality, Neurology 17 (5) (1967) 427e442, 10.1212/WNL.17.5.427:1526-632X. [22] A. Nieuwboer, L. Rochester, T. Herman, et al., Reliability of the new freezing of gait questionnaire: agreement between patients with Parkinson's disease and their carers, Gait Posture 30 (4) (2009) 459e463, https://doi.org/10.1016/ j.gaitpost.2009.07.108. [23] Z.S. Nasreddine, N.A. Phillips, V. Bedirian, et al., The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment, J. Am. Geriatr. Soc. 53 (2005) 695e699, https://doi.org/10.1111/j.15325415.2005.53221.x. [24] M.J.D. Caetano, J.C. Menant, D. Schoene, P.H.S. Pelicioni, D.L. Sturnieks, S.R. Lord, Sensorimotor and cognitive predictors of impaired gait adaptability in older people, J. Gerontol. A Biol. Sci. Med. Sci. 72 (9) (2017) 1257e1263, https://doi.org/10.1093/gerona/glw171. [25] J. Jankovic, Parkinson's disease: clinical features and diagnosis, J. Neurol. Neurosurg. Psychiatry 79 (4) (2008) 368e376, https://doi.org/10.1136/ jnnp.2007.131045. [26] H. Bokura, S. Yamaguchi, S. Kobayashi, Event-related potentials for response
38
M.J.D. Caetano et al. / Parkinsonism and Related Disorders 47 (2018) 32e38
inhibition in Parkinson's disease, Neuropsychologia 43 (6) (2005) 967e975, https://doi.org/10.1016/j.neuropsychologia.2004.08.010. [27] P. Praamstra, D.F. Stegeman, A.R. Cools, M.W. Horstink, Reliance on external cues for movement initiation in Parkinson's disease. Evidence from movement-related potentials, Brain 121 (1) (1998) 167e177, https://doi.org/ 10.1093/brain/121.1.167. [28] J.M. Hausdorff, G.M. Doniger, S. Springer, G. Yogev, E.S. Simon, N. Giladi, A common cognitive profile in elderly fallers and in patients with Parkinson's disease: the prominence of impaired executive function and attention, Exp. Aging Res. 32 (4) (2006) 411e429, https://doi.org/10.1080/ 03610730600875817. [29] D.F. Hultsch, S.W. MacDonald, R.A. Dixon, Variability in reaction time
performance of younger and older adults, J. Gerontol. B Psychol. Sci. Soc. Sci. 57 (2) (2002) P101eP115, https://doi.org/10.1093/geronb/57.2.P101. [30] R.A. Miller, M.H. Thaut, G.C. McIntosh, R.R. Rice, Components of EMG symmetry and variability in parkinsonian and healthy elderly gait, Electroencephalogr. Clin. Neurophysiol. 101 (1) (1996) 1e7, https://doi.org/10.1016/ 0013-4694(95)00209-X. [31] A. Burleigh-Jacobs, F.B. Horak, J.G. Nutt, J.A. Obeso, Step initiation in Parkinson's disease: influence of levodopa and external sensory triggers, Mov. Disord. 12 (2) (1997) 206e215, https://doi.org/10.1002/mds.870120211. [32] J.M. Hausdorff, J.D. Schaafsma, Y. Balash, et al., Impaired regulation of stride variability in Parkinson's disease subjects with freezing of gait, Exp. Brain Res. 149 (2) (2003) 187e194, https://doi.org/10.1007/s00221-002-1354-8.