The Effect of Various Cognitive-Motor and Motor-Motor Tasks on the Motor and Cognitive Function of Patients Multiple Sclerosis: A Randomized Controlled Trial

Background: 85% of multiple sclerosis patients suffer from impaired motor function and 65% from cognitive impairment. Therefore The main purpose of this study is to improve the cognitive and motor function of patients using dual tasks. Methods: The study samples were 60 women with MS (20-50 years) with an Expanded Disability Status Scale 2-4 and the duration of the period (10-14 years) who were divided into 4 groups and for eight weeks each week including two sessions 45 They practiced dual cognitive, motor, and individual training for 45 to 60 minutes. Data were analyzed by composite variance analysis at signicance level of P <0.05. Results: The results of compound analysis analysis showed that the training of cognitive-motor tasks improved the signicance of motor function (p = 0.0005) and cognitive performance (p = 0.0001) compared to the other three groups. Conclusion: The results of this study suggest that the physical benets of training are always superior to cognitive changes. Dual-task training can be considered a good way to improve cognitive and cognitive function.

Trial registration: This study was registered in the Iranian Clinical Trial Center with the number IRCT20200812048384N1, http://www.irct.ir/trial/50300, registered 26 August 2020.

Background
Multiple Sclerosis (MS) is a type of progressive degenerative disease of the myelin sheath in Central nervous system (CNS) [1]. Despite advances in medical science in recent years, the MS has already had no de nitive treatment, and most of the available treatments lead to a reduction in symptoms or a reduction in the rate of disease progression, so it prevents the rapid diagnosis and detection of disease and its timely control of it. Symptoms range from a wide range that can be referred to as weakness of muscles, Ataxia, spasm, vision disorders, sensory disorders, and cognitive disorders [2], as well as reducing mobility abilities and fatigue from the underlying problems. More than 85% of these patients suffer from walking and non -balance problems [4], and when these problems are accompanied by a cognitive task [5]. As a result, physical and cognitive functions are important parts of a successful motor function. However, the impairment of the physical domain [6,7] and cognitive domains [8], observed in MS, may lead to related disorders that may result in the inability to manage daily activities.
Integration between movement and cognitive domains is measured using the dual-task (DT) model, which refers to the ability to perform two simultaneous tasks [8,9]. In particular, these two tasks refer to motor tasks (e. g. task math) and an additional task at the same time, from any range of cognition (e. g. a mathematical task)or movement type (e.g., holding a glass of water) [10]. Researchers recommend that the placement of individuals in the interest -sharing situations (i.e., DT) helps them plan appropriate control strategies [11]. DT's performance is related to most of the everyday life activities and the inability of patients to perform e cient tasks may have different consequences. Recently, several studies have been conducted on healthy elderly people [12][13][14][15] or in people with mental illnesses (e.g., Parkinson's disease) [16] using DT exercises, whose results showed improvement of balance and walking. indirectly, the bene ts of walking and learning separately indicate that performance in these tasks can be improved in patients with targeted interventions. Speci cally, DT training in patients with dementia and Parkinson's disease show that by training purposeful DT, motor and cognitive impairment can be minimized.
The aim of this study was to investigate the effect of DT training on motor and cognitive function in MS patients. In particular, we sought to investigate the effect of cognitive-motor (CM), motor-motor (MM) and single task (ST) on motor components (walking, balance), cognitive component (speed and accuracy of information processing) and psychological components (quality of life (QOL), anxiety and depression). In particular, we hypothesized for overall improvement in motor and cognitive function in both DT conditions after 16 DT training sessions. In addition, previous studies have suggested that participants who undergo MM DT training do not differ signi cantly in motor factors from the other three groups and ST and MC groups.

Method
Trial design This single-blind, randomized, and controlled trial, which was conducted at Iran MS Society rehabilitation centre in Tehran, Iran, lasted for 8 weeks starting in October and ending in November 2019. Participants were blinded to the type of exercise and the intervention group. This study included three steps: 1. Preintervention measurements 2. 8-week DT and ST training for case groups, And the control group resumed their normal lives, and 3. Post-intervention measurements.
Prior to the intervention, participants were tested for berg balance tests (BBT), time-to-up and go (TUG) tests, quality of life questionnaires, anxiety and depression, and Stroop information processing tests.
Participants were randomly divided into four groups of 15 ( Fig. 1).

Figure 1 Participant Flow Diagram
The participants in this study were patients with MS in Tehran province. Using G-Power software with a test power of 0.8, the effect size was 0.8 and the error level was 0.05, the sample size was 60 people. Sampling was also available and 60 eligible participants were selected from 78 participants. Conditions for entering the study range are 20-50 years, EDSS (2-4), disease period (10)(11)(12)(13)(14), recurrence in recent months (at least one month), non-addiction to drugs and alcohol, no fractures and joint and movement problems and The ability to recognize English colours in the Stroop test. Participants were informed that their participation in the study was voluntary and con dential and that they could leave the study at any time without any problems.

Study intervention
After the pre-test and identifying the groups, our intervention began. group (1), CM tasks that simultaneously performed a cognitive task (such as counting backwards) and a motor task (such as walking over an obstacle); (2) the dual MM tasks performed by two simultaneous motor tasks (such as walking and wearing a heater), the ST group (3) performing only walking training, and (4) the control of their daily lives. Participants practised for 8 weeks, including 2 sessions per week and 45-60 minutes per session, and nally, the pre-test tests were used again in the post-test period. It should be noted that the basic movement training in all 3 experimental groups (or walking), which was constant in 3 training groups, includes the following 10 items that have been borrowed from functional gait assessment (FGA): Going to safety, changing speed, walking with a head turn, walking with a back turn, walking 180 turns, stepping on obstacles, walking with minimal support, walking blindfolded, walking backwards, and stairs.
In the CM DT training group, FGA was associated with cognitive training that included counting backward numbers, counting coins and paper money, texting, multiplying and dividing numbers, and naming the solar months from beginning to end. Participants changed from simple to di cult.
In the MM DT Training Group, FGA merged with the most commonly used daily movement training, such as tying coat buttons, wearing clothes, tying watches, hanging clothes on hangers, and carrying a cup of water.
In this study, the ST force practiced only the FGA movement task, and the control group lived a normal life during the intervention. Before each training session, the instructors explained and performed the training, and all of the proposed training were complexes in terms of complexity, tailored to the individual abilities of the participants.
It should be noted that all the trains were performed in the form of circular training for more e ciency, and each person went to the next movement after the speci ed time of each movement (30 seconds of activity and 45 seconds of rest until the start of the next movement). As the participants' level of performance increased, the ratio of training time to rest increased.

Randomization and blinding
In this study, participants were randomly divided into 4 groups according to the days they could come to the gym. It should be noted that none of the factors involved in the study were blind.

Measurement
Demographic data (age, height, weight, disease duration, EDSS, and BMI) were collected. Before the test, each participant was assessed for height and weight (Table 1). All research was conducted in a xed location and the instructors were constant throughout the study.
The walking speed was measured using the TUG eld test, which is a simple test to assess people's mobility and requires static and dynamic balance. The balance was measured using a berg balance test, which is a clinical trial to assess static and dynamic balance, especially in neurological patients. Patients' quality of life was measured with the MSIS-29 questionnaire, which contains 29 questions, the rst 20 questions of physical impact and the last 9 questions of the psychological impact of MS on the patient. Participants' anxiety and depression were also measured by the hospital's anxiety and depression questionnaire. This 4-item selection questionnaire was designed to measure mood swings, especially anxiety and depression. Finally, patient information processing was measured by an online strop test. The online test has 20 questions. The 15 names and color questions are con ict with each other, and the 5 name and color questions are the same. And the output of this test is presented in the form of a table that shows the number of correct questions and the time of the test. Statistical Analysis IBM spss25 software was used for statistical analysis. To determine the mean and standard deviation, descriptive statistics were used to normalize the data from Azen Shapiro-Wilk and to compare between groups, assuming that the composite analysis of variance was parametric and in all cases the signi cance level was p < 0.05.

Results
There were no side effects during the study, and most of the participants who participated in the training from the beginning completed the study. post-test groups showed a better depression anxiety score than the control group (p < 0.05). But this was not the case in the MM group (p < 0.05). The CM training group also showed better depression anxiety scores in the post-test than the other two training groups (p < 0.05). However, no signi cant differences were observed between the two groups of MM training and ST in anxiety scores Post-test depression was not observed (p < 0.05).
Diagram 6. Comparison chart of the dependent variable of anxiety, the depression between the four control groups, CM task, MM task and ST in the pre-test and post-test stages.

Discussion
The aim of this study was to investigate the effect of a CM and MM, DT training program on the motor function of MS patients. For this purpose, we examined the effects of 8 weeks of DT training with secondary motor and cognitive tasks in a sample of MS individuals to examine the effect of DT on the motor and cognitive function of MS patients. In particular, we evaluated performance at walking speed, balance, information processing, quality of life, and anxiety and depression in ST and DT conditions. The present study sought to develop previous work in several ways. First, limited studies used DT as a training method. Second, using the other form of DT is a MM training on the patients that this type of exercise is more important to patients with brain loss -spinal cord injuries, elderly people and Parkinson's patients, which is, of course, important that the results are contradictory and we intended to make comparisons between the two practice methods to achieve a speci c result. The results of the present study showed that an 8-week program improved the condition of the CM training group in all factors compared to the other three groups. The MM training group and the ST group did not differ signi cantly from each other except in the information processing (accuracy) section in the other factors studied. Also, the three training groups had a signi cant difference in balance, walking speed and quality of life compared to the control group. In terms of information processing accuracy, the CM group and the MM group were better than the control group. Also, the CM group was better than the MM group, but the MM group did not have a signi cant difference with the ST group. All four groups did not have a signi cant difference in post-test information speed and processing. In the following, we will review and compare several studies in this eld. Closed eyes are more useful than other methods, and these results are somewhat at odds with the present study because we found in the balance discussion that the CM group achieved a signi cant improvement in balance over other groups [19].
Finally, the justi cation for the lack of difference between the two groups of MM and ST can be attributed to 10 items of FGA training. During the intervention, patients reported that FGA walking training was very cognitive for them and that walking was not done automatically. For example, in walking training over the patient's obstacles, they needed to identify the distance to the obstacle, adjust the step, and choose a support base, which in turn imposed a lot of cognitive load on the participants.
Also, the better performance of the CM group in the factors of quality of life, anxiety and depression can be attributed to the interesting and challenging cognitive training.
The reason why this research is inconsistent with our study can be due to the intervention, disability and type of disease of patients, gender and differences in the form of exercises that are debatable.
Doing two tasks at the same time requires attention to resources and integration of executive performance [20],Therefore, we may speculate that MS patients who have enrolled in our DT practice may learn to manage their attention between these two tasks [21]. In fact, two independent streams of visual information, one related to the walking task and the other related to the secondary task, must be synchronized [22]. Participants in CM, DT training may improve task management and coordination skills to perform two tasks simultaneously [23]. Therefore, our results suggest that CM, DT training may alter the DT strategy and lead to better and more e cient integration of the two tasks [24].

Conclusion
As a result, our results suggest that 8 weeks of CM, DT training can improve motor, cognitive, quality of life, and anxiety, and depression in patients in relation to ST and MM -DT groups. In no other case did the processing of information differ signi cantly. However, further studies using larger sample sizes appear to be necessary to expand this study and integrate gender. Our results as a DT training, including secondary cognitive tasks, may improve patients' motor and cognitive function. To understand the role of certain types of training, focusing on DT function for people with MS, it may be helpful for older people to develop speci c strategies and guidelines for speci c interventions.

Limitations
Several potential limitations of this study should be considered. First, all patients in the study were female and the sex was not integrated. Second, the relatively small size of the sample does not allow us to generalize our results to a larger population. The use of FGA testing as a basic motor exercise in all 3 groups, this test could affect the results of the study due to the di culty of the items and the need for cognitive activity to perform. And last but not least, the cost of dual homework in all three groups. Although these ndings support the predominant effect of our training protocol on physical aspects, the bene ts of cognitive training are not clear.

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