The Effect of Integrated Aerobic and Cognitive Training (Activ4Brain) on Cognition and Neurophysiology in Older Adults: Protocol for a Controlled Trial.

Background: There is a need for efficient and engaging strategies that will mitigate the effects of aging on cognitive and physical functions while keeping users motivated for long-term adherence. Objective: This study protocol is designed to investigate, in older adults, the advantage of integrating cognitive training with aerobic exercise (AE) in fun group sessions to potentiate the effect of training on cognition while improving physical function. The protocol explores the effects of a novel intervention, the Activ4Brain program, on cognition and physical function as well as the underlying neurobiological mechanisms. Methods: The program consists of group AE classes that include computerized games designed to train cognition during exercise, taking advantage of exercise-induced arousal. Cognitive training task difficulty is adapted throughout the intervention as users improve their performance. Importantly, the setup allows for simultaneous body movements to maintain aerobic activation. This is a 3-arm controlled trial, using a parallel design with a 1:1:1 allocation to an experimental group that is engaged in the Activ4Brain program (24 sessions, twice a week), an active control group that is engaged in AE sessions, and a passive control group. Participants are tested at baseline and after the intervention. The main study outcome is changes in cognition. Additional outcomes include changes in brain and autonomic function, levels of inflammation and neuroprotective markers, cardiovascular and physical functional fitness, and body composition. Results: Data collection started in January 2024 and finished in April 2025. Seventy-three individuals (40 women and 33 men) were enrolled in the study and assigned to the 3 groups. The average age was 66 (SD 6) years. Data analyses are ongoing, with the publication of the results estimated for 2026 and 2027. Conclusions: This study will produce knowledge important for the development of efficient strategies to fight age-related decline.