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Parkinson's Disease and Cognitive-Motor Dual-Task: Is Motor Prioritization Possible in the Early Stages of the Disease?

ABSTRACT The authors aimed to compare the postural phase of gait initiation under single-task (gait initiation) and dual-task (gait initiation plus Stroop test) conditions in healthy subjects and in subjects with Parkinson's disease (PD) in the early stages (Hoehn and Yahr scale < 3). The postural phase of gait initiation was assessed through the centre of pressure in single and dual task in 10 healthy subjects and 9 with PD. The analysis indicated that in the early stages of PD, an additional cognitive task did not affect the displacement of the gait initiation. No significant effects occurred between the groups and within-subjects (p > .05). Also, no interaction was found between the groups and the conditions (single- and dual-task). Differences were found in the duration of the mediolateral postural phase (p = .003), which was higher in PD subjects than in healthy subjects. The findings suggest that subjects in the early stages of PD prioritize gait initiation, as their motor performance was similar to that of healthy subjects.

A dual-task condition involves the execution of two tasks simultaneously. One is the main task, and the other is the secondary task (Kelly, Eusterbrock, & Shumway-Cook, 2012b;Nocera, Roemmich, Elrod, Altmann, & Hass, 2013;Sethi & Raja, 2012). The performance of two tasks simultaneously leads to a competition for limited resources that results in the deterioration of the performance of one or both tasks (Kelly et al., 2012a;Wu & Hallett, 2009).
Biomechanical studies of postural stability have demonstrated that in a dual-task condition, subjects with Parkinson's disease (PD) exhibit impaired postural control. In addition, some authors have suggested that the dual-task condition restricts their anticipatory postural adjustments (APAs) to focus on the cognitive task without losing balance (Nocera et al., 2013;Yogev-Seligmann et al., 2010).
Postural phase of gait initiation (GI) is associated to the interval between the first vertical impulse, due to the APAs, until the maximum center of pressure (CoP) displacement backward and toward the first swing limb. It is characterized by a backward displacement of CoP that results from the APAs causing a forward displacement of the centre of gravity (Caderbya et al., 2013;Yiou, Caderby, & Hussein, 2012). Subjects with PD often have difficulties in generating APAs, particularly in forward propulsion and lateral weight shift when initiating gait (Hall, Brauer, Horak, & Hodges, 2013). Studies involving subjects with PD have shown that the duration of APAs is extended, the backward and lateral displacements of the CoP are reduced and the length and velocity of the first step are shortened (Burleigh-Jacobs, Horak, Nutt, & Obeso, 1997;Crenna et al., 2006;Gantchev, Viallet, & Aurenty, 1996;Hall et al., 2013;Halliday, Winter, Frank, Patla, & Prince, 1998;Rogers et al., 2011), increasing the risk of falls (Kelly et al., 2012a;Schmit et al., 2005).
Difficulties in performing two tasks simultaneously may be associated with impairment of executive function and attention deficits, which are characteristics of PD (Hausdorff et al., 2006). When subjects with PD focus on the motor performance, they can perform normal patterns of movement by activating the uninjured premotor cortex and not using the injured basal ganglia circuit, thereby ensuring the performance of movements. However, in dual-task condition, the use of cortical resources to carry out motor tasks may compromise or influence the performance of one or both tasks (Holmes, Jenkins, Johnson, Adams, & Spaulding, 2010a;Kelly et al., 2012a;Wu & Hallett, 2009).
Furthermore, several studies have revealed higher instability in upright standing in individuals over 65 years old with and without any pathology, which becomes more notorious in the individuals after stage 3 of PD (Tsutiya et al., 2011). However, there is a lack of information about the early stages of PD as well as the influence of the dual-task in GI. Therefore, the aim of this study was to compare the postural phase on GI in single-and dual-task conditions in healthy subjects and in subjects in the early stages of PD (Hoehn and Yahr scale < 3). Therefore, the anteroposterior and mediolateral CoP displacements, the anteroposterior and mediolateral velocities of the CoP displacements, and the anteroposterior and mediolateral durations of the postural phase were assessed.

Subjects
A cross-sectional study was implemented using a nonprobabilistic convenience sample (Doherty, 1994) of nine subjects with PD and 10 healthy subjects, between 52 and 80 years old. The size of the sample used is in line with other studies of this kind, such as the studies of Nocera et al. (2013), with 13 PD individuals; Halliday et al. (1998), with 10 PD individuals; Holmes et al. (2010a), with 12 PD individuals; Rogers et al. (2011), with 8 PD individuals; Schmit et al. (2005), with six PD subjects; Hiraoka, Matsuo, Iwata, Onishi, and Abe (2006), with nine PD subjects; and Hiraoka, Matsuo, and Abe (2005), with 11 PD subjects. The subjects diagnosed with PD were patients from the Parkinson's Association in Porto, Portugal, while the healthy controls were community-dwelling volunteers mainly from Porto, Portugal.
Subjects were excluded if they presented one of the following factors: incapable of walking independently (based on the Timed Up and Go test [TUG] score until 10 s; Podsiadlo & Richardson, 1991), unable to speak, and severe cognitive impairment (screened with the Montreal Cognitive Assessment [MoCA]; Hoops et al., 2009). The option for the MoCA test was based on the study by Chou et al. (2010), who analyzed five statistical tests and recommended it as a standard cognitive screening instrument to be used in clinical trials with PD patients. The reasons for this recommendation are that it can be performed quickly and has the potential to identify subtle executive dysfunctions, while covering the major cognitive domains. Severely disabled PD patients (>3 Hoehn and Yahr Scale; Hoehn & Yahr, 1967), patients diagnosed with any other neuromuscular disease, or those who had undergone deep brain stimulation through subthalamic surgery or were under cholinergic medication were also excluded. Healthy subjects that have been diagnosed as adults with any neuromuscular disorder or that cannot be considered sedentary, according to the Centers for Disease Control for the American College of Sports Medicine, were also excluded (Pate et al., 1995).
A trained researcher conducted the data collection based on a structured protocol. The study was approved by the Ethical Review Board of the Escola Superior de Tecnologia da Sa ude-Instituto Polit ecnico do Porto, in Portugal. Written informed consent, according to the Helsinki Declaration, was obtained from all subjects.

Instruments
The data collected from all subjects included sociodemographic characteristics (age, gender, height, weight, and level of education), years of disease, cognitive performance (assessed by the MoCA test), functional mobility (evaluated using the TUG test), number of colors correctly named and errors according to the Stroop test, and values in terms of the Hoehn and Yahr scale (Hoehn & Yahr, 1967).
The Hoehn and Yahr scale (Hoehn & Yahr, 1967) is commonly used to assess the severity of overall dysfunction in PD subjects. It is a 7-point scale, in which each point represents a different stage of the disease (stages 1-5, including 1.5 and 2.5). The scale increases with the severity of dysfunction along with the stage of the disease.
The values of the vertical, anteroposterior and mediolateral components of the ground reaction forces (GRF) were obtained from a force platform, model FP4060-8 from Bertec Corporation (), according to a sampling rate of 1000 Hz (Hanke & Rogers, 1992). The platform was connected to a Bertec AM 6300 amplifier (Colombus, OH) and in turn, this was connected to an analog-digital converter from Biopac Systems, Inc. (Santa Barbara, CA), and to an analog board of Qualisys Track Manager (G€ oteborg, Sweden) that can be used for stabilometric analyses. The force platform signals were digitized and stored for subsequent analysis in Acqknowledge (Biopac Systems, Inc.).

Procedures
After an explanation of all the procedures involved, all individuals performed the tasks with shorts and standard shoes (sneakers with laces) that were provided for the study to be similar for all individuals. In the single-task condition, the subjects were asked to remaining in the standing position for 30 s, looking at a point at eye level 2 m away. After this interval, the subjects were instructed to walk three steps at a self-selected speed. In the dual-task condition, the previous procedures were repeated; however, the subjects were required to perform the Stroop test simultaneously, which consisted of naming the color used to print the name of a different color (Romann, Dornelles, Maineri, Rieder, & Olchik, 2012). The order of each condition (single-and dual-task) changed randomly, from individual to individual, to avoid a learning effect. There was a 1-min rest between each trial, and all necessary repetitions were performed to obtain three valid trials to reduce the within-individual variability and increase the statistical power (Mullineaux, Bartlett, & Bennett, 2001). All the experimental data were acquired by the same trained researcher to ensure reproducibility.
The CoP signal was low-pass filtered with a fourth-order Butterworth filter (zero-phase lag) with a cutoff frequency of 8 Hz (Winter, 2009). The postural phase was defined as the interval between the starting of the CoP displacement (T0) until the maximum CoP displacement backward and toward the first swing limb. The T0 was identified as the instant when the CoP signal deviated from the baseline (obtained in standing position) plus three standard deviations for a minimum interval of 50 ms (Shiratori & Latash, 2001). The end of the postural phase was defined as the instant associated to the first deflection of the CoP displacement (Tsukahara, Kawanishi, Hasegawa, & Sankai, 2010).
The values of the anteroposterior CoP displacement (CoP AP ) and mediolateral CoP displacement (CoP ML ), anteroposterior duration of the postural phase (Duration AP ) and mediolateral duration of the postural phase (Duration ML ), and anteroposterior velocity of the CoP displacement (Vel AP ) and mediolateral velocity of the CoP displacement (Vel ML ) were used for analysis.

Statistical Analysis
According to the nature of the variables under study, descriptive statistical analyses were performed using proportions and measures of central tendency and dispersion. All the variables analyzed presented a normal distribution, so multivariate analysis of variance (MANOVA) for repeated measures was used for multivariance analysis between healthy subjects and PD subjects in the single-and dual-task conditions, and all variables were assessed simultaneously. For additional evaluations, the independent samples t test was used to obtain results regarding the differences for the various conditions between groups, while paired samples t test was used to analyze the differences between the single-and dual-task conditions in each group. Two-tailed tests were used in all analyses done and p < .05 was adopted for statistical significance. All statistical analyses were run using SPSS version 22.0 (SPSS Inc., Chicago, IL).

RESULTS
The PD sample had nine subjects (66.7% male), with a mean age of 66 years old (SD D 8.2 years), a mean education of 7.7 years (SD D 5.1 years), and a mean years of disease of 10.22 (SD D 5.38 years). Most of these subjects were classified as stage 1 and 1.5 of the Hoehn and Yahr scale, with a mean of 8.39 s (SD D 0.86 s) in the TUG test. The healthy sample had 10 subjects (50% male), with a mean age of 63.7 years (SD D 7.6 years) and a mean education of 8.2 years (SD D 4.5 years). When both groups were compared, statistically significant differences were only found in the number of the colors correctly named on the Stroop test. PD subjects scored less than the healthy subjects, Table 1.
The analysis of repeated measures MANOVA, indicated that there were no significant multivariate effects between the healthy and PD subjects studied, F(6, 11) D 2.030, p > .05, h p 2 D .525, nor within subjects independently of their group, F(6, 11) D 0.973, p > .05, h p 2 D .347. Also, no relation was found between the groups and conditions, F(6, 11) D 0.982, p > .05, h p 2 D .349. Univariate analysis between the groups indicated that the Duration ML was significantly higher for the PD subjects than for the healthy subjects, F(1, 16) D 12.494, p D .003, h p 2 D .44. A significant relation was found between the conditions and groups for the Duration ML , F(1, 16) D 4.717, p D .045, h p 2 D .228.
Although the CoP AP and Vel ML did not present significant differences between the groups, large between-group effects were found (h p 2 D .07 and h p 2 D .08, respectively). Considering the within-group univariate analysis, no differences were detected between the single-and dual-task conditions. Nerveless, within the healthy group, large effect sizes (d) were found for the Duration ML , Duration AP and Vel ML , and small for the CoP AP , CoP ML , and Vel AP . Within the Parkinson's group, the effect sizes (d) were large for the Duration ML , medium for the Duration AP and small for the CoP AP and Vel AP , Table 2.
The significant relations found were explored further. In the dual-task condition, the PD subjects had a significantly higher Duration ML than the healthy subjects, t(17) D ¡3.536, p D .003. When single-and dual-task conditions were compared, no significant difference was found between the conditions in subjects with PD. However, in healthy subjects, the Duration ML was significantly lower in the dual-task condition than in the single-task condition, t (9) D ¡2.496, p D .034 (Figure 1).

DISCUSSION
The aim of this study was to compare the postural phase of GI in single-and dual-task conditions in healthy subjects and in PD subjects in the early stages of the disease (Hoehn and Yahr scale < 3). In contrast to what was expected, no significant differences were observed between subjects with PD and healthy subjects regarding the CoP AP , CoP ML, VelCoP AP , and VelCoP ML . However, the mean CoP AP and CoP ML displacements were lower in the subjects with PD.
Previous studies of APAs associated with GI have shown that the backward CoP displacement might be significantly reduced in PD subjects (Breniere, Do, & Bouisset, 1987;Elble, Moody, & Leffler, 1994;Nocera et al., 2013). This leads to an extension of the first swing phase and to a decrease in the length of the first step and in the walking speed (Yiou et al., 2012). In this study, the mean values of CoP ML also decreased in PD subjects, as was observed in the studies by Yiou et al. (2012) and Nocera et al. Also, the mean values of Vel AP and Vel ML found were less in PD subjects, which is in line with those obtained by Halliday et al. (1998) and Gantchev et al. (1996). Deficits in APAs of PD subjects have been linked to abnormal muscle activation patterns characterized by an extension of excitatory and reduced inhibitory activity as well as a delay in its onset or even loss of muscular activation or deactivation (Crenna et al., 2006;Crenna & Frigo, 1991).
Besides the nonexistence of statistically significant differences between the healthy and PD subjects, no variable was significantly influenced by the dual-task condition in the PD group. These findings are surprising considering the frequent and consistent negative effect of dual-task on motor performance in PD subjects (Bloem, Grimbergen, van-Dijk, & Munneke, 2006;Holmes et al., 2010a;Yiou et al., 2012). Some authors have postulated that the nature of this neurodegenerative disease and the cognitive demands of a dual-task condition would limit the performance of one or both tasks (Morris, 2000;Rogers et al., 2011). Thus, before doing this study, it was expected that in GI, the motor performance of the PD subjects would be altered, even in individuals at the initial stage of the disease. Nevertheless, a nonsignificant difference between the single-and dual-task conditions in GI of PD subjects was also observed in the study by Nocera Nocera et al. (2013. The nonexistence of significant differences between groups obtained in the present study suggests that the PD sample was able to prioritize the motor task in detriment of the cognitive task. This was evidenced by the number of colors correctly named, which was significantly lower in the PD subjects than in the healthy subjects. It is important to note that no differences occurred between the two groups in terms of education and the MoCA test (Kelly et al., 2012b;Souza, Voos, Francato, Chien, & Barbosa, 2013). The MoCA test was applied to both groups to give an indication whether the subjects had cognitive deterioration or not and to detect differences of cognitive deterioration between the PD group and the healthy controls before the evaluation, to validate the findings and conclusions of the present study.
Moreover, the lack of differences between the healthy and PD subjects may be due to the fact that the underlying anticipatory muscular synergy was preserved and the lower CoP displacement and velocity was probably related to the slowness of execution (i.e., to bradykinetic episodes; Berardelli, Rothwell, Thompson, & Hallett, 2001). In fact, this  study found that the CoP ML duration was longer and significantly different for the PD subjects than the healthy subjects. Furthermore, for the healthy subjects the postural phase duration increased in the dual-task condition in relation to the single-task condition. Also these results corroborate other studies suggesting that PD subjects have a lower CoP AP , a higher duration of the postural phase, and that the APAs start later during GI in the dual-task condition than in the single-task condition (Carpinella et al., 2007;Nocera et al., 2013;Yiou et al., 2012). In the same subjects, the CoP AP duration tends to decrease from the single-to dual-task conditions. This decrease has been described as an ineffective strategy for maintaining balance, as it causes decreased backward CoP displacements, resulting in higher risk of falls (Holmes et al., 2010a;Kelly et al., 2012a;Nocera et al., 2013;Schmit et al., 2005). The fact that the PD subjects under study did not show any differences between the single-and dual-task conditions can also be explained by a greater focus on the motor task, which means that the motor performance is not debilitated despite the worse results in the Stroop test.
In the literature, most studies to characterize the motor deficits in PD subjects have used subjects in advanced stages of the disease and only in the single-task condition. However, most activities of daily living require the simultaneous execution of a cognitive task. Nevertheless, differences between durations were found. In particular, this study indicates that the behavior of individuals in the early stages of PD may retain the ability to prioritize tasks and choose the motor task in detriment of the cognitive task. However, it is necessary understand if this prioritization is automatic or it is caused consciously by the individual to prevent falls. Therefore, future studies related to the stage of disease in the performance of motor and cognitive tasks independently and simultaneously are essential to clarify this doubt.

Clinical Relevance
This study corroborated that subjects with PD take longer to perform mediolateral displacements, especially in dualtask condition. On the other hand, the mediolateral and anteroposterior displacements found in the subjects with PD were similar to the ones found in the controls. These results indicate that in the early stages of PD, the cognitive performance can be impaired when performing cognitive motor dual tasks. Thus, the interventions should not be only focused on the motor performance, which is currently considered the main attention of the interventions, but should also include cognitive training.

Limitations
This study had some limitations. First, the small sample size and the sampling method can limit the results in regard to generalizations, that which leads us to consider it as an exploratory study. Second, the potential interference of the experimental environment on the GI of the subjects studied could affect the results obtained. Hence, further studies with larger samples and in different experimental environments are needed.