Computerized Games versus Crosswords Training in Mild Cognitive Impairment.

BACKGROUND: Mild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear.

METHODS: In a two-site, single-blinded, 78-week trial, participants with MCI - stratified by age, severity (early/late MCI), and site - were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.

RESULTS: Among 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, -1.44; 95% confidence interval [CI], -2.83 to -0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, -2.45; SE, 0.89; 95% CI, -4.21 to -0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, -1.08; 95% CI, -1.97 to -0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]).

CONCLUSIONS: Home-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.).