Computerized Cognitive Rehabilitation of Executive Deficits in Stroke Patients

Study Overview
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Brief Summary
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WHO: 32 participants with executive deficits related to a stroke, able to engage in moderate physical activity. WHY: Around one third of stroke patients suffer from cognitive deficits in the long term, which have a detrimental impact on everyday personal and professional life. The purpose of this study is to evaluate two sets of computerized exercises combining cognitive and physical effort to see if they can improve executive function. WHAT: Study participants first undergo cognitive and physical assessments. Additional questionnaires will assess mood, everyday life cognition, function and quality. This will be followed by a 6 week training period with 3 training sessions a week. The effect of the cognitive and physical training will be measured in a post-training evaluation session. Six months after completion of the training, the study will evaluate cognitive and physical abilities of participants to study long-term effects of the respective training program. WHERE: Both the evaluation and the training sessions will be conducted on the premises of the Centre Hospitalier Universitaire Vaudoise (Pavillon 4, Avenue de Beaumont, 1005 Lausanne, Switzerland)

Detailed Description
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This is an exploratory Randomized Controlled Trial with the purpose of evaluating the potential of two sets of gamified cognitive and physical exercises in the neurorehabilitation of cognitive deficits following a stroke. Upon recruitment, eligible study participants (see 'Eligibility Criteria') receive a detailed oral and written description about the scientific background, aims and methods of the study. Additional information will be provided about potential benefits and risks associated with study participation, as well as about the voluntary nature of participation throughout the study. The participant's written informed consent is required for study enrollment. After inclusion in the study, participants are randomized into one of two different training programs with equal chance of attribution and without possibility of choosing: Program 1 involves brain training games with a physical exercise component. Program 2 involves cognitive training games with a physical exercise component. Independently of program attribution, participants engage in a pre-training assessment, a six-week training period, a post-training assessment and a 6-month-follow-up assessment. Before the start of the training, participants are required to perform several cognitive and physical tests and fill out a number of questionnaires on subjective cognitive function, mood and quality of life. The exercises and the questionnaires serve as a baseline evaluation of cognitive and physical function. Following the first assessment, study participants engage in a 6-week training period. In both programs, participants engage in 3 weekly trainings of 90 minutes duration each. After completion of the training period, study participants engage in a post-training assessment to evaluate the effect of training on cognitive and physical performance. This session incorporates the same tasks and questionnaires as in the pre-training visit. The aim of the post-training assessment is to demonstrate immediate training effect of the two programs. A final follow-up visit is scheduled 6 months after the completion of the last training session. The cognitive and physical testing together with the questionnaires will be repeated to examine the long-term effects of the training programs.

Official Title
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Combined Cognitive and Physical Training for the Neurorehabilitation of Executive Deficits After Stroke: an Exploratory Randomized Controlled Trial

Conditions
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Stroke, Executive Dysfunction

Intervention / Treatment
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* Device: Computerized Gaming Rehabilitation Program 1
* Device: Computerized Gaming Rehabilitation Program 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Ischemic or haemorrhagic cerebral stroke ≥ 8 weeks before study inclusion Cognitive complaint and/or clinical impression of dysexecutive syndrome Z-Score < -1.0 in at least two of the following domains Cognitive flexibility (Trail-Making Test B/A) Cognitive interference (Stroop color word interference task) Divided attention (TAP divided attention) Working memory (TAP working memory, Forward Digit Span, Backward Digit Span) Design fluency (Five-points test) Exclusion Criteria: Major neurocognitive disorder according to the DSM-5 Proximal extremity paresis grade < M4 on the Medical Research Council (MRC) Scale for Muscle Strength in at least one of four extremities Insufficient visual acuity, visual field or hemispatial attention to engage in the training Inability to discriminate colour: < 12 points on the Ishihara test Changes over the last 4 weeks in antidepressive, anxiolytic or in acetylcholinesterase inhibitor drugs Thoracic pain and/or heart palpitations at rest, during or following a physical effort (based on self-report) Clinically unstable cardio-vascular disease Falls in the past 12 weeks as evaluated in the enrolment interview [Hopkins Falls Grading Scale (Grade >1)] High risk of falling according to a score of over 15 seconds on the Four Square Step Test (FSST) Insufficient knowledge or capacity of French to follow instructions Incapacity or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Program 1<br>Computerized Gaming Rehabilitation Program 1 | Device: Computerized Gaming Rehabilitation Program 1<br>* Brain training games with physical exercise component.<br>|
| Experimental: Program 2<br>Computerized Gaming Rehabilitation Program 2 | Device: Computerized Gaming Rehabilitation Program 2<br>* Cognitive training games with physical exercise component.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive interference after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Cognitive interference is measured using the Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, Kramer, 2001) Stroop Test | 6 weeks | 
| Change in divided attention after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Divided attention is measured using the Test of Attentional Performance (TAP, version 2.3.1; Zimmermann and Fimm, 2002) subtest for divided attention | 6 weeks | 
| Change in visuospatial working memory after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Visuospatial working memory is measured by the immediate recall of the Brief Visuospatial Memory Test-Revised (BVMT-R; Benedict, 1996) | 6 weeks | 
| Change in subjective executive function after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Subjective executive function is measured by the Working Memory Questionnaire (WMQ; Vallat-Azouvi et al, 2012; 30 items, participants rate 10 statements on storage, attention and executive domain on a Likert-scale from 1-5 (not at all - extremely)) | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual working memory after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Visual working memory will be assessed via performance on the computerized 'Filter task' (Vogel, 2005). | 6 weeks | 
| Change in design fluency after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | The Five-Point Test (Regard, 1982) will be used to assess design fluency. | 6 weeks | 
| Change in processing speed after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | The Trail-Making-Test Part A (Reitan, 1955) will be used to assess processing speed. | 6 weeks | 
| Change in cognitive flexibility assessed by the TMT-B after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Cognitive flexibility will be measured using the Trail-Making-Test B (TMT-B; Reitan, 1955). | 6 weeks | 
| Change in cognitive flexibility assessed by the TAP Flexibility after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Cognitive flexibility will be measured using the subscale 'Flexibility' of the Test of Attentional Performance (TAP, version 2.3.1; Zimmermann and Fimm, 2002) | 6 weeks | 
| Change in cognitive inhibition after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | The Test of Attentional Performance (TAP, version 2.3.1; Zimmermann and Fimm, 2002) subtest Go/NoGo will assess cognitive inhibition. | 6 weeks | 
| Change in cognitive multitasking after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | A subtest of a custom-made tablet-based cognitive evaluation tool will measure cognitive multitasking. | 6 weeks | 
| Change in covert shift of attention after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Measured by the corresponding subtest of the Test of Attentional Performance (TAP, version 2.3.1; Zimmermann and Fimm, 2002). | 6 weeks | 
| Change in risk of falls and postural stability after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Postural stability and risk of falls will be assessed using the BTrackS Balance Plate (FDA registered class 1 medical device #3010668481) | 6 weeks | 
| Change in dynamic stability after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Dynamic stability will be assessed by the Four Square Step Test (FSST; Dite et al, 2002), which tests the participant's ability to step over objects forwards, sideways and backwards; the movements of the FSST are comparable to the ones implemented in the training program. | 6 weeks | 
| Change in ability to perform a cognitive and physical dual task after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | In order to assess cognitive and motor dual task ability, the study participant will perform the 'Timed Up and Go Cognitive' subtest from the MiniBESTest (Franchignoni et al, 2010). | 6 weeks | 
| Change in heart rate after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Heart rate (HR) will be recorded at rest in supine position during a 5-minute window using a chest belt. | 6 weeks | 
| Change in heart rate variability after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Heart rate variability (HRv) will be recorded at rest in supine position during a 5-minute window using a chest belt. | 6 weeks | 
| Change in systolic and diastolic blood pressure after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Determined by the mean of three blood pressure measurements using a sphygmomanometer and a stethoscope. | 6 weeks | 
| Everyday physical activity during 6-week training period. | Measuring daily step count and minutes of daily activity using a wrist-attached wearable device will determine everyday physical acitivity during the training period. | 6 weeks | 
| Change in everyday life quality after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Study participants will rate everyday life quality using the Quality of Life after Brain Injury questionnaire (QOLIBRI; von Steinbuchel, 2010; 36 items originally, adapted to 35 items for stroke, participants rate applicability of statements on quality of life after stroke from not at all to very)) | 6 weeks | 
| Change in everyday life cognitive function after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Study participants will rate everyday life cognitive function using the Cognitive Failure Questionnaire (CFQ; Broadbent, 1982; 25 items, participants rate the frequency of situations representing cognitive dysfunction in the past 6 months from very often (4 points) to never (0 points), a lower score represents a better subjective cognitive function). | 6 weeks | 
| Change in mood after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Mood is measured by the Hospital Anxiety and Depression Scale (HAD-S; Zigmond and Snaith, 1983), which tests for both anxiety and depression in a 14-item questionnaire (7 items each, participants rate statements on a Likert-Scale from 0-3 for each statement, the maximal score is 28 for each domain, the cut-off 11 for anxiety and depression is points or more). | 6 weeks | 
| Change in apathy after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Study participants will rate their degree of apathy using the self-administered Dimensional Apathy Scale (DAS; 24 items; Radakovic and Abrahams, 2014). | 6 weeks | 
| Change in fatigue after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | Study participants will rate their degree of fatigue on the Modified Fatigue Impact Scale (MFIS; Larson, 2013; 21 items in total, whereof 9 items on a physical subscale, 10 items on a cognitive subscale and 2 items on a psychosocial subscale; every item contains a statement rated on a Likert-Scale from 0-4 (never - almost always), a higher score represents a greater impact of fatigue on the participant's life) | 6 weeks | 
| Change in subjective balance after a 6 weeks period of gamified cognitive and physical training (program 1 vs program 2) | The subjective balance of study participants will be measured using the Tinetti Falls Efficacy scale (Tinetti, 1990), a 10-item questionnaire. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurological Rehabilitation, Stroke Rehabilitation, Cognitive Behavioural Therapy, Exercise Therapy, Brain Training, Nervous System Diseases, Neurocognitive Disorders, Cognition Disorders, Mental Disorders, Vascular System Injuries, Cerebrovascular Disorders