Online Cognitive Training in PD, MS and Depressed Patients Treated With Electroconvulsive Therapy

Study Overview
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Brief Summary
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In Parkinson's disease, Multiple Sclerosis and depressed patients treated with electroconvulsive therapy, cognitive dysfunction is prevalent. However, treatment of these dysfunctions is in its infancy. The purpose of this study is 1) to assess the feasibility of a randomized controlled trial using an online computerized intervention for training cognitive abilities in the three patient groups and 2) to estimate the effect of the online training on objectively and subjectively measured cognitive functions. The investigators hypothesize that patients using online cognitive training will improve more on cognitive functions, as compared to patients using an active control condition.

Detailed Description
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In neurodegenerative disorders and psychiatric disorders, cognitive dysfunction is frequently reported. In Parkinson's disease (PD), Multiple Sclerosis (MS) and patients treated with electroconvulsive therapy after a severe or therapy resistant depression (postECT), executive dysfunction, attention deficit or episodic/autobiographic memory deficit is prevalent. In MS and PD, these dysfunctions can appear already early in the disease. The majority of PD patients - lifetime prevalence is about 80% - develops PD dementia. In MS, about half of the patients experiences problems with cognitive functions. ECT is used to treat patients with severe and/or therapy resistant depression. However, 30-50% of these patients develops severe cognitive dysfunction. Recovery usually occurs within six months after ECT. However, performances remain below-average compared to norm groups and there are large individual differences. The cognitive difficulties in MS and PD have a significant negative influence on the quality of life. Cognitive dysfunction in PD is associated with decreased independent daily functioning, hospitalization and the development and severity of neuropsychiatric symptoms. Furthermore, in the clinic cognitive dysfunction has been reported to be one of the most dreadful side effects of ECT. However, effective treatment of the described cognitive dysfunction is still in its infancy. Cognitive training is based upon the principle that plasticity of the brain can facilitate function improvement by intensive training. In several neurological diseases, cognitive training has shown significant improvement in cognitive functions. In MS and PD, earlier studies have been small, frequently without an adequately controlled design. Additionally, earlier cognitive training programs have frequently been executed in a health care organization, impairing patients to successfully attend all training sessions due to mobility impairments. Also, there are limited studies in the effects of cognitive training on improved functioning of daily living and neuropsychiatric symptoms like anxiety and depression. Given the fact that there is an absence in cognitive training studies in patients post-ECT, there is no knowledge about the ability of cognitive training to speed up the natural course. Using this pilot study, the investigators aim to study the feasibility of a randomized controlled trial using an online computerized intervention for training cognitive abilities in three patient groups. By using a double-blinded, controlled study design, the investigators keep in mind limitations of earlier comparable studies. If this treatment proves to be feasible, and a rough estimated effect size is positive, a larger randomized controlled trial can be executed to study the effectivity of this treatment. When effects are positive, an online cognitive training programme could prove to be a cost-efficient intervention that is accessible at home - something which is important for patients with mobility problems. The investigators hypothesize that patients using online cognitive training will improve more on cognitive functions, as compared to patients using an active training condition.

Official Title
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Clinical Pilot Study in the Feasibility and Effect of Online Cognitive Training on Cognitive Functions in Patients With Parkinson's Disease, Multiple Sclerosis and Depressive Patients Treated With Electroconvulsive Therapy

Conditions
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Idiopathic Parkinson's Disease, Multiple Sclerosis, Elderly Post Electric Convulsive Therapy

Intervention / Treatment
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* Behavioral: Online cognitive training
* Behavioral: Active control condition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General criteria: Patients have (access to) a computer with access to the Internet. Patients are capable of using a keyboard and computer mouse. Patients are willing to sign informed consent. PD-specific criteria: A compilation score of executive functions (i.e. Stroop, Trail Making Task, Fluency) shows deficit, which lies between 1 and 2 standard deviation (SD) below the mean of healthy Dutch norm population. Patients are diagnosed with Parkinson's disease according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. Patients are in Hoehn & Yahr stadium < 4, and are medically stable during a month prior to the intervention. The medication will be attempted to remain stable for the remainder of the intervention. Patients are 50 to 70 years old. MS-specific criteria: A compilation score of episodic memory (i.e. Rey Auditory Verbal Learning Test, Location Learning Test) shows deficit, which lies between 1 and 2 SD below the mean of healthy norm population. Patients have been diagnosed with MS for a period longer than three month prior to inclusion in this study according to the renewed McDonald criteria. Patients have been on stable medication for at least three months. Patients are 30 to 45 years old. PostECT-specific criteria: Unipolar depressive patients indicated for ECT, who experience cognitive complaints after treatment with ECT. Patients have undergone the full ECT-procedure. Phonemic fluency and autobiographical memory (measured by the Kopelman Autobiographical Interview) show deficit: significant individual deterioration is present (> 1.5 SD deterioration), accounting for test- retest effects. Patients are 50 to 70 years old. Exclusion Criteria: General criteria: Indications for presence of dementia. Presence of traumatic brain injury. A psychiatric disorder (in the postECT group: other than unipolar depression). No history or presence of drug or alcohol abuse. Inability to undergo a neuropsychological assessment (e.g. due to fast fatigue, seeing problems or language barrier). PD-specific criteria: - Psychotic symptoms, as screened by the Questionnaire for Psychotic Experiences (QPE). Benign hallucinations with insight are not contraindicated). MS-specific criteria: - Patients with MS can't have relapses or can't use corticosteroids 4 weeks prior to the start of the study. postECT-specific criteria: - Indications for presence of delirium.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-Experimental<br>PD patients using the online cognitive training for 8 weeks, 3 times a week | Behavioral: Online cognitive training<br>* The intervention is a computerized, online training programme which aims to train several cognitive abilities; especially the executive functions, attention, working memory and processing speed. The mental processes that are appealed to by the intervention are similar to processes that are trained in classic face-to-face training methods. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>* Other names: BrainGymmer, Dezzel Media B.V., The Netherlands;|
| Active Comparator: PD-Control<br>PD patients using the active control condition for 8 weeks, 3 times a week | Behavioral: Active control condition<br>* The active control condition consists of cognitive activities that do not intend to train cognitive functions based on 'cristallized intelligence', such as trivia. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>|
| Experimental: MS-Experimental<br>MS patients using the online cognitive training for 8 weeks, 3 times a week | Behavioral: Online cognitive training<br>* The intervention is a computerized, online training programme which aims to train several cognitive abilities; especially the executive functions, attention, working memory and processing speed. The mental processes that are appealed to by the intervention are similar to processes that are trained in classic face-to-face training methods. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>* Other names: BrainGymmer, Dezzel Media B.V., The Netherlands;|
| Active Comparator: MS-Control<br>MS patients using the active control condition for 8 weeks, 3 times a week | Behavioral: Active control condition<br>* The active control condition consists of cognitive activities that do not intend to train cognitive functions based on 'cristallized intelligence', such as trivia. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>|
| Experimental: postECT-Experimental<br>Depressed elderly treated with ECT patients using the online cognitive training for 8 weeks, 3 times a week | Behavioral: Online cognitive training<br>* The intervention is a computerized, online training programme which aims to train several cognitive abilities; especially the executive functions, attention, working memory and processing speed. The mental processes that are appealed to by the intervention are similar to processes that are trained in classic face-to-face training methods. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>* Other names: BrainGymmer, Dezzel Media B.V., The Netherlands;|
| Active Comparator: postECT-Control<br>Depressed elderly treated with ECT patients using the active control condition for 8 weeks, 3 times a week | Behavioral: Active control condition<br>* The active control condition consists of cognitive activities that do not intend to train cognitive functions based on 'cristallized intelligence', such as trivia. Both the intervention protocol and the active control condition will contain several games that have the participant train cognitive functions/perform cognitive activities for 8 weeks, 3 times a week, 45-60 minutes each session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | The feasibility of the intervention as reported by the patients on 4-point Likert scale items (T1) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trail Making Task | Cognitive functioning as assessed by neuropsychological measures. These are measured by the interaction effect between time of measurement (T0 versus T1, or T0 versus T2) and condition (experimental versus active control). If possible, parallel tests will be used to correct for repeated neuropsychological testing. The objectively measured intervention effect will be assessed on the most affected cognitive domain, different per syndrome: - PD and postECT: improvement in executive functions, measured by change in the Trail Making Task | Baseline, 8 weeks and 12 weeks | 
| Cognitive functioning (subjectively measured) | Change in subjective cognitive complaints as reported by the patient, measured by the Cognitive Failure Questionnaire (CFQ) | Baseline, 8 weeks and 12 weeks | 
| Feasibility | The feasibility of the intervention as reported by the patients in a group session lead by patients from the disease associations. | Patients will be interviewed in a group session after study completion, an expected average of half a year | 
| Stroop Color Word Task | Cognitive functioning as assessed by neuropsychological measures. These are measured by the interaction effect between time of measurement (T0 versus T1, or T0 versus T2) and condition (experimental versus active control). If possible, parallel tests will be used to correct for repeated neuropsychological testing. The objectively measured intervention effect will be assessed on the most affected cognitive domain, different per syndrome: - PD and postECT: improvement in executive functions, measured by change in the Stroop Color Word Test. | Baseline, 8 weeks and 12 weeks | 
| Letter Fluency | Cognitive functioning as assessed by neuropsychological measures. These are measured by the interaction effect between time of measurement (T0 versus T1, or T0 versus T2) and condition (experimental versus active control). If possible, parallel tests will be used to correct for repeated neuropsychological testing. The objectively measured intervention effect will be assessed on the most affected cognitive domain, different per syndrome: - PD and postECT: improvement in executive functions, measured by change in the Letter Fluency. | Baseline, 8 weeks and 12 weeks | 
| Rey Auditory Verbal Learning Test | Cognitive functioning as assessed by neuropsychological measures. These are measured by the interaction effect between time of measurement (T0 versus T1, or T0 versus T2) and condition (experimental versus active control). If possible, parallel tests will be used to correct for repeated neuropsychological testing. The objectively measured intervention effect will be assessed on the most affected cognitive domain, different per syndrome: - MS: improvement in episodic memory, measured by change in the Rey Auditory Verbal Learning Test. | Baseline, 8 weeks and 12 weeks | 
| Location Learning Test | Cognitive functioning as assessed by neuropsychological measures. These are measured by the interaction effect between time of measurement (T0 versus T1, or T0 versus T2) and condition (experimental versus active control). If possible, parallel tests will be used to correct for repeated neuropsychological testing. The objectively measured intervention effect will be assessed on the most affected cognitive domain, different per syndrome: - MS: improvement in episodic memory, measured by change in the Location Learning Test. | Baseline, 8 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Multiple Sclerosis, Depressed Elderly, Cognitive Dysfunction, Online Cognitive Training