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

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).

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Multi-domain cognitive training; Behavioral: Cross-word puzzle training

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 120954; 5K25AG050759 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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