Effects of 24-week Computerized Cognitive Training in Patients With MCI and AD

Study Overview
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Brief Summary
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This study aims to testify multi-domain effects of computerized cognitive training in patients with mild cognitive impairment and mild Alzheimer's disease through multi-dimensional evaluation.

Detailed Description
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This study aimed to elucidate the neural process enhancement and remodulation in gut microbes resulting from older adults with MCI and mild AD in a randomized controlled trial of a 24-week computerized cognitive training (CCT) program. After recruitment and baseline assessments, pairs of participants with MCI and mild AD would be randomly allocated into the corresponding subgroup. Participants in CCT group will receive a computerized multidomain cognitive training program (www.66nao.com) and will be required to complete at least 30 minutes of training per day (3 cycle of 5 2-min tasks), 5 days a week for 24 weeks. Adherence to the intervention will be supervised by an independent researcher. The number of training days and training hours per day will be recorded. Patients in control group received treatment as usual (TAU) for 24 weeks. The neuropsychological measures will be performed at baseline, follow-up at 4 weeks, 12 weeks, and 24 weeks; functional Near-Infrared Spectroscopy (fNIRS) data and fecal samples will collected at baseline and 24 weeks.

Official Title
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Effects of 24-week Computerized Cognitive Training on Microbiota-gut-brain Axis in Patients With Mild Cognitive Impairment and Mild Alzheimer's Disease: a Randomized Controlled Trial

Conditions
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Mild Cognitive Impairment, Alzheimer Disease

Intervention / Treatment
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* Other: Computerized Cognitive Training
* Other: Treatment As Usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between 55 and 90 years of age; a Clinical Dementia Rating (CDR) score of 0.5 or 1; at least three months of stable doses if receiving antidementia medication or mood-stabilizing medication for mild AD participants; primary school education and above; accompanied by a consistent caregiver (at least 5 days/week); informed consent. Exclusion Criteria: factors that might preclude completion of assessments; severe psychiatric illness and the use of antidepressants; any condition that would preclude completion of training and follow-up tests; other disorders that would affect cognition.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 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
Interventional Model Description: After recruitment and baseline assessments, pairs of participants with MCI and mild AD will be randomly allocated into either the CCT group and the control group. Participants in CCT group will receive a multidomain adaptive computerized cognitive training program (www.66nao.com) for 24 weeks. Patients in control group will receive treatment as usual (TAU) for 24 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computerized Cognitive Training<br>Adaptive computerized cognitive training program (www.66nao.com) and the intensity is at least 30 minutes of training per day (3 cycle of 5 2-min tasks), 5 days a week for 24 weeks. | Other: Computerized Cognitive Training<br>* Participants in intervention group will receive a multidomain, adaptive computerized cognitive training program (www.66nao.com) and will be required to complete at least 30 minutes of training per day (3 cycle of 5 2-min tasks), 5 days a week for 24 weeks. Multidomain coverage paradigms include working memory, calculation, processing speed, attention, executive function, and short-term and long-term memory.<br>|
| Active Comparator: Treatment As Usual<br>Patients in control group will receive TAU for 24 weeks, which includes (1) regular medication management from the Memory Clinic, if applicable; (2) basic health education at each follow-up (face to face) and twice per month on the internet. | Other: Treatment As Usual<br>* Patients in control group will receive TAU for 24 weeks, which includes (1) regular medication management from the Memory Clinic, if applicable; (2) basic health education at each follow-up (face to face) and twice per month on the internet .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Cognition | The Alzheimer's Disease Assessment Scale- cognitive subscale (11 items) will be used to evaluate global cognition and served as the primary outcome measure. The minimum and maximum values are 0 and 70 respectively, and higher scores mean a worse outcome. | baseline, 4, 12, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Learning | The Auditory Verbal Learning Test (minimum to maximum: 0-45) will be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Episodic Memory | The Free and Cued Selective Reminding Test (minimum to maximum: 0-48) will be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Attention | The Trail Making Test (minimum to maximum: 0-24) will be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Executive Function | The Digital Span Test (minimum to maximum: 0-10) will also be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Visuospatial Function | The Clock Drawing Test (minimum to maximum: 0-15) will be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Verbal Ability | The Boston Naming Test (minimum to maximum: 0-30) will be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Verbal Frequency | The Verbal Frequency Test (minimum: 0, no maximum) will also be applied, and higher scores mean a better outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Neuropsychiatric Symptoms | The Neuropsychiatric Inventory (minimum to maximum: 0-144) will be used, and higher scores mean a worse outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Depression | The 30-Geriatric Depression Scale (minimum to maximum: 0-30) will be used, and higher scores mean a worse outcome for the scale. | baseline, 4, 12, 24 weeks | 
| Daily Living Function | The Instrumental Activities of Daily Living scale (minimum to maximum: 0-31) will be used, and higher scores mean a worse outcome for this scale. | baseline, 4, 12, 24 weeks | 
| Severity of Cognitive Impairment | The Clinical Dementia Rating scale (sum of boxes, minimum to maximum: 0-18) will be used, and higher scores mean a worse outcome for this scale. | baseline, 4, 12, 24 weeks | 
| Brain Functional Connectivity | The regions of interests (ROIs) are selected as the Brodmann Area (BA) 9 and 46 (overlapping the dorsolateral prefrontal cortex, DLPFC), left Brodmann Area 6 (overlapping pre-Motor and Supplementary Motor Cortex, PM-SMC), and right Brodmann Area 45 (overlapping pars triangularis Broca's area). For each resting-state dataset of fNIRS, functional connectivity (FC) will be analyzed by Spearman's correlation between the time series of each ROI-to-ROI pair. | baseline and 24 weeks | 
| Alpha-diversity of Gut Microbiome | Fecal samples will be collected from patients in standard 300 mL sterilin tubes and frozen immediately at -80°C. Patients will be asked to produce the first-morning sample for consistency and to avoid alcohol the previous 24 h. After 16S rRNA high-throughput sequencing, the diversity analysis of species under a sample (α-diversity) of the bacteria on Genus, will be analyzed in R. | baseline and 24 weeks | 
| Beta-diversity of Gut Microbiome | After 16S rRNA high-throughput sequencing, the cluster analysis between different samples (β-diversity) will be analyzed in R. | baseline and 24 weeks | 
| Composition of Gut Microbiome | After 16S rRNA high-throughput sequencing, the compositional analysis of bacteria on genus will be analyzed in R. | baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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computerized cognitive training, functional near-infrared spectroscopy, mild cognitive impairment, Alzheimer's disease, brain-gut-microbiota axis, gut microbiota