The Influence of Multi-domain Cognitive Training on Large-scale Structural and Functional Brain Networks in MCI

Study Overview
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Brief Summary
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The purpose of this study is to integrate advanced computational techniques and multimodal neuroimaging methods to examine the potential effects of long-term, multi-domain, online, computerized cognitive training on large-scale structural and functional brain networks in older adults with mild cognitive impairment (MCI).

Detailed Description
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This multilevel study will be comprised of a placebo controlled randomized controlled trial to test the effect of long-term (6 months), multi-domain, computerized cognitive training on large-scale structural and functional brain networks in individuals with MCI (age >= 65 years). Neuroimaging and neuropsychological data before and after intervention will be evaluated within and between groups to elucidate the trajectory of neuronal network improvements associated with training compared to typical MCI development. We will compare the outcomes between participants with MCI who receive structured cognitive training (treatment group: TG) with those who receive nonspecific computerized training activities (active controls: AC). The duration of intervention is 6 months. The focus of the study will be on individuals with amnestic MCI (single- or multi- domain). The study includes 30 MCI subjects in a treatment group (TG) and 30 matched MCI subjects in active control (AC) group. TG and AC participants will be evaluated at two time points: 1) baseline and 2) 6-month (post-training).

Official Title
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The Influence of Multi-domain Cognitive Training on Large-scale Structural and Functional Brain Networks in MCI

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Multi-domain cognitive training
* Behavioral: Cross-word puzzle training


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Cognitive concern by subject, informant or physician Impairment in memory domain (delayed recall of one paragraph from Logical Memory II subscale from Wechsler memory Scale - Revised with cutoff scores of <=8, <=4 and <=2 for 16, 8-15 and 0-7 years of education) Essentially normal functional activities Mini-Mental State Examination (MMSE) scores >=24 Stability of permitted medications (e.g. cholinesterase inhibitors, hypertension medication, etc.) for at least two months. Exclusion criteria: Any significant neurological condition including probable dementia, Parkinson's disease, Huntington's disease, multiple sclerosis, and brain tumor, among others. Presence of Axis I disorder Current use of psychoactive medications except for the permitted medications. Claustrophobia MRI contraindication Any significant systemic or unstable medical condition which could lead to difficulty complying with the protocol.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treatment group will receive 6 months of online, computerized, multi-domain cognitive training at home. | Behavioral: Multi-domain cognitive training<br>* The cognitive exercises are designed to train executive functions and memory.<br>|
| Active Comparator: Active Control<br>The Active Control group will receive 6 months of online, computerized cross-word puzzles at home using the same platform as for the Treatment group. | Behavioral: Cross-word puzzle training<br>* The active control group will be asked to complete a variety of crossword puzzles using the same curriculum assigned to the TG group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Executive function composite score | The primary behavioral outcome is executive function composite score that combines measures of working memory, inhibition, set-shifting, and fluency | 6 months | 
| Executive function network connectivity | The primary neuroimaging outcome is the interconnectivity of the frontal-striatal-parietal network. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory function composite score | Memory function composite score that combines measures of auditory verbal learning and episodic memory | 6 months | 
| Medial temporal network connectivity | Regional interconnectivity and centrality in medial temporal network | 6 months | 
| White matter integrity in memory circuit | White matter integrity in posterior cingulate-medial temporal-frontal pathways | 6 months |