Cognitive-motor Intervention Using Virtual Reality for Middle-aged Individuals at High Dementia Risk

Study Overview
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Brief Summary
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The primary objective of this program is to apply a virtual reality (VR) cognitive-motor intervention (compared to active and passive control groups) to delay or slow cognitive decline of middle-aged adults who have a family history of Alzheimer's disease (AD) and thus are at particularly high risk of developing the disease.

Official Title
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Cognitive-motor Intervention Using Virtual Reality for Middle-aged Individuals at High Dementia Risk

Conditions
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Alzheimer's Disease (AD)

Intervention / Treatment
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* Behavioral: cognitive training by virtual reality
* Behavioral: watching a scientific TV documentary
* Device: treadmill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participants of the study must have at least one parent with Alzheimer's disease. Fluency in Hebrew, in order to understand the instructions of the cognitive tests. Availability of an informant for the participant. Exclusion Criteria: Severe neurological or psychological conditions that may affect cognitive performance. Substantial orthopedic limitations which prevent the use of treadmill. Unstable medical condition such as an active cancer. Incapability of adherence to the training program. The participant is undergoing a treatment that may interfere with the study program.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VR cognitive tasks + treadmill<br>This is the primary group of interest, in which the investigators hypothesize the greatest cognitive gains since motor activity will augment cognitive activity. | Behavioral: cognitive training by virtual reality<br> <br> Device: treadmill<br>* VR cognitive training will be augmented by walking on a treadmill, since it is well established that dual tasking-i.e. performing the VR-based cognitive effort together with a motor task, even as simple as walking on a treadmill-places greater demand on cognitive resources than a single task.<br>|
| Active Comparator: VR cognitive tasks - treadmill<br>This group will be an active control, receiving the VR cognitive training without treadmill walking, to examine whether the motor component augments the effect of the VR in the experimental group. | Behavioral: cognitive training by virtual reality<br> <br> |
| Sham Comparator: scientific TV documentary + treadmill<br>This group will watch a scientific TV documentary while walking on the treadmill. This control group will permit examination of whether the VR cognitive training, which requires an especially active cognitive effort while walking on the treadmill, is more advantageous than passively watching a scientific TV documentary while performing the same motor task as the experimental group. | Behavioral: watching a scientific TV documentary<br> <br> Device: treadmill<br>* VR cognitive training will be augmented by walking on a treadmill, since it is well established that dual tasking-i.e. performing the VR-based cognitive effort together with a motor task, even as simple as walking on a treadmill-places greater demand on cognitive resources than a single task.<br>|
| No Intervention: Passive control<br>This group of participants will not receive any intervention but will be assessed with the same battery of assessments as the other three groups, permitting comparisons of the cognitive and neurobiological outcomes of the intervention groups to that of the natural course of decline/deterioration of these at-risk individuals. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in overall cognition- measured by averaging z-scores from 14 paper and pencil neuropsychological tests covering episodic memory and executive functions cognitive domains. | summary of the z-scores of all 14 paper and pencil cognitive tests | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| change in cerebral blood flow from arterial spin labeling (ASL) | acquired by structural MRI using background-suppressed pseudo-continuous ASL (pcASL) featuring a 3D fast spin echo spiral sequence | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| specific cognitive domains- average of z-scores of paper and pencil memory tests and of executive functions tests | summary of z-scores of executive functions tests and of episodic memory tests | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| blood oxygenation level dependent (BOLD) functional MRI (fMRI) signal in the fronto-parietal network associated with working memory | T2*-weighted fMRI during an n-back working memory task; contrasts: 1-back minus 0-back; 2-back minus 0-back; 2-back minus 1-back | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| brain resting state functional connectivity by resting state network fMRI BOLD signal correlations | T2*-weighted fMRI while relaxing with eyes closed; functional connectivity between seed regions of resting state networks (e.g., default mode, attentional, salience) and other regions by correlation of BOLD signal in seed regions with that in other regions | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| hippocampal volume | 3D T1-weighted MRI imaging | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| frontal inferior cortex volume | 3D T1-weighted MRI imaging | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| white matter hyperintensity (WMH) burden | 3D T2-FLAIR MRI imaging | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 
| diffusion-tensor imaging (DTI) measures | diffusion-weighted MRI imaging (DWI) to map white matter tractography | baseline, immediately after 12-week training, and 3 months post-training (or corresponding time points in passive control group) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, virtual reality, cognitive training