Computerized Cognitive Training for MCI

Study Overview
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Brief Summary
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The objective of the study is to evaluate whether memory training combined with executive training could lead to improved cognitive and noncognitive performance in patients with MCI. Furthermore, we will explore the neural correlates underlying the changed performances.

Detailed Description
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Introduction: Mild cognitive impairment (MCI) is a clinical condition characterized of a reduction in memory and/or other cognitive processes that are insufficiently severe to be diagnosed as dementia, but are more pronounced than the cognitive decline associated with normal aging. The prevalence of MCI ranges from 3% to 19% in adults older than 65 years; some of these individuals seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Thus, MCI represents a critical window of opportunity for intervening and altering the trajectory of both cognitive decline and loss of functional independence in older adults. Cognitive function apart from memory such as executive function is also impaired in patients with MCI. However, no study has yet placed sufficient emphasis on the training of executive function. Objectives: The objective of the study is to evaluate whether memory training combined with executive training could lead to improved cognitive and noncognitive performance in patients with MCI. Furthermore, we will explore the neural correlates underlying the changed performances. Patients and Methods: The proposed study is a single blinded, randomized and controlled trial that will include 120 elderly patients with MCI from the memory clinic. The groups will be randomized to either intervention or waiting-list group. The intervention is computerized combined memory and executive function training performed for 60 minutes x 4 times/week over 26 weeks. A neuropsychological assessment will be administered at baseline and week 4, 12 and 26 after the intervention. The structural and functional MRI, EEG and NIRS will be performed at baseline and week 26 after intervention for a sub-study on the effect of cognitive training on brain structure and function.

Official Title
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A Randomized Control Trial on Computerized Cognitive Training for Individuals With Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Device: Combined executive function and memory training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An objective cognition impairment (a Montreal Cognitive Assessment (MoCA) score < 26) Preserved general cognitive function( an mini-mental state examination (MMSE) score of > 24) Clinical Dementia Rating (CDR) = 0.5 Hamilton Depression Scale (HAMD) score of < 12 Intact activities of daily living (ADL score of <=26) Schooling education > = 5 years) Not meeting the diagnosis of dementia (according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) Probable Alzheimer's Criteria Exclusion Criteria: Serious visual or hearing impairment; Hachinski Ischemia Scale (HIS) >= 4; Subjects with Axis I disorders listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), any other neurological disorders that could affect cognitive function; currently on titration of medications with cognitive enhancers or antidepressants; having any physical condition that could preclude regular attendance and full intervention-program participation

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 89 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined cognitive training<br>The training is combined executive function and memory training. The training is considered 'adaptive', which means that the difficulty level of the tasks increases during the sessions according to the individual level of mastering for each participant, making the patient work at their maximum capacity at all times. | Device: Combined executive function and memory training<br>* Computerized combined executive function and memory training<br>|
| No Intervention: Waiting-list group<br>Participants in the control condition will conduct the same training as the intervention group after a 26-week waiting period. During the 26-week waiting period, the participants will receive assessment with the same protocol as the interventional group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite working memory z score | composite score of digit span and spatial span | Change from baseline composite working memory z score at week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cognitive test package (CTP) | composite score of episodic memory, speed processing, executive function, attention, language and social cognition | Changes from baseline composite CTP score at week 26 | 
| Self evaluated memory ability | Score on the questionnaire probes worries about memory (MMQ-contentment). | Change from baseline self evaluated memory ability at week 26 | 
| Brain Functional Imaging | Brain function measured with MRI. | change from baseline functional connectivity at week 26 | 
| Electrical activity of the brain | Brain activity measured with electroencephalography (EEG). | change from baseline electrical brain activity at week 26 | 
| Brain structural imaging | cortical thickness measured with MRI | change from baseline cortical thickness at week 26 | 
| cerebral blood flow | Cerebral blood flow measured with Near-infrared spectroscopy (NIRS). | change from baseline cerebral blood flow at week 26 | 
| Mood | composite score of mood status | Change from baseline composite mood score at week 26 | 
| BDNF level | Serum Brain-derived neurotrophic factor (BDNF) level | change from baseline serum BDNF level at week 26 | 
| Composite of overall cognition z scores | Score on Montreal Cognitive Assessment (MoCA) and Mini-mental State Examination (MMSE). | Changes from baseline composite overall cognition z score at week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Computerized, Executive function, memory, cognitive training, Mild Cognitive Impairment