Impact of Computerized Cognitive Training on Default Mode Network Connectivity in Subjects at Risk for Alzheimer's Disease: A 78-week Randomized Controlled Trial.

BACKGROUND: Mild cognitive impairment (MCI) represents a high risk group for Alzheimer's disease (AD). Computerized Cognitive Games Training (CCT) is an investigational strategy to improve targeted functions in MCI through the modulation of cognitive networks.

OBJECTIVE: The goal of this study was to examine the effect of CCT versus a non-targeted active brain exercise on functional cognitive networks.

METHODS: 107 patients with MCI were randomized to CCT or web-based crossword puzzles. Resting-state functional MRI (fMRI) was obtained at baseline and 18 months to evaluate differences in fMRI measured within- and between-network functional connectivity (FC) of the default mode network (DMN) and other large-scale brain networks: the executive control, salience, and sensorimotor networks.

RESULTS: There were no differences between crosswords and games in the primary FC outcome. However, secondary analyses suggest differential effects on between-network connectivity involving the DMN and SLN, and within-network connectivity of the DMN in subjects with late MCI. Paradoxically, in both cases, there was a decrease in FC for games and an increase for the crosswords control (p < 0.05), accompanied by lesser cognitive decline in the crosswords group.

CONCLUSION: Results do not support a differential impact on within-network DMN FC between games and crossword puzzle interventions. However, crossword puzzles might nonspecifically engage multiple specialized cognitive networks at a low level, resulting in cognitively beneficial remodeling between the DMN and other networks, and within the DMN in subjects at higher risk of dementia.