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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Feb 3, 2026
Open Peer Review Period: Feb 3, 2026 - Mar 31, 2026
Date Accepted: Jul 16, 2026
(closed for review but you can still tweet)

The final, peer-reviewed published version of this preprint can be found here:

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

Besikci H, Akalp K, Rama L, Gomes BB, Ferreira JPL, Mouga S, Bernardino I, Castelo-Branco M, Sousa e Silva AR, Teixeira AM, Ribeiro MJ

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

JMIR Res Protoc 2026;15:e92631

DOI: 10.2196/92631

PMID: 42752398

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

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

  • Hicran Besikci; 
  • Kaan Akalp; 
  • Luís Rama; 
  • Beatriz Branquinho Gomes; 
  • José Pedro Leitão Ferreira; 
  • Susana Mouga; 
  • Inês Bernardino; 
  • Miguel Castelo-Branco; 
  • Ana Rita Sousa e Silva; 
  • Ana Maria Teixeira; 
  • Maria José Ribeiro

ABSTRACT

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 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 aerobic exercise 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 three-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 aerobic exercise 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 three groups. The average age was 66 ± 6 (mean ± standard deviation) 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. Clinical Trial: Trial registry:Clinicaltrials.gov Registration number: NCT07108413 URL of registry: https://clinicaltrials.gov/study/NCT07108413


 Citation

Please cite as:

Besikci H, Akalp K, Rama L, Gomes BB, Ferreira JPL, Mouga S, Bernardino I, Castelo-Branco M, Sousa e Silva AR, Teixeira AM, Ribeiro MJ

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

JMIR Res Protoc 2026;15:e92631

DOI: 10.2196/92631

PMID: 42752398

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