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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Other: Computerized Cognitive Training; Other: Treatment As Usual

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • The First Affiliated Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Computerized Cognitive Training; 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; 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.
Active Comparator: Treatment As Usual; 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; 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 .

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chongqing Medical University
• Investigators: Principal Investigator: Weihua Yu, Dr., Chongqing Medical University

Publications and helpful links

Helpful Links

• The trail has also been registered under chictr.org.cn (ChiCTR2100051362).

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Actual): August 19, 2022
• Study Completion (Actual): August 19, 2022

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; mild cognitive impairment; gut microbiota; functional near-infrared spectroscopy; computerized cognitive training; brain-gut-microbiota axis
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: ChongqingMU9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: With publication of research articles, de-identified data collected for the study, including individual participant data, can be made available to interested parties on reasonable request, and if in line with privacy regulations. Data can be requested at least 18 months after publication of the research articles, with a proposal by sending an e-mail to Dr. Yang Lü.
• IPD Sharing Time Frame: Data can be requested at least 18 months after publication of the research articles.
• IPD Sharing Access Criteria: With publication of research articles, de-identified data collected for the study, including individual participant data, can be made available to interested parties on reasonable request, and if in line with privacy regulations, with a proposal by sending an e-mail to Dr. Yang Lü.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No