Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity: The ActiveBrains Randomized Clinical Trial.

Importance: Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. Objectives: To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. Design, Setting, and Participants: All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. Interventions: All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. Main Outcomes and Measures: Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. Results: The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. Conclusions and Relevance: In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified. Trial Registration: ClinicalTrials.gov Identifier: NCT02295072.