The 'Brain-IT' project was my doctorate project under the supervision of the Principal Investigator of the project, Prof. Dr. Eling D. de Bruin in the Motor Control & Learning laboratory at ETH Zurich. The project was funded by Synapsis Foundation - Dementia Research Switzerland (grant 2019-PI06) and "Gebauer Stiftung", and financially supported by “Fondation Dalle Molle”. 

The core project was completed in April 2024, however, we still have  some ongoing data analyses on the effects of the 'Brain-IT' training on structural and functional changes in the brain as measured by magnetic resonance imaging, which we expect to complete and submit for publication early 2025.

Introduction: Effective interventions to mitigate one of the key challenges for aging societies, neurocognitive disorders, are urgently needed. A collaborative international guideline recently recommended physical exercise (PE) for secondary prevention of mild neurocognitive disorder (mNCD). Physical exercises that integrate cognitive exercises and are combined with resonance breathing guided by heart rate variability biofeedback (HRV-BF) target various relevant mechanisms of action to alleviate the pathological state in mNCD. However, this novel intervention approach has not yet been investigated.

Methods: We first introduced a novel methodology based on which we designed, developed, and evaluated of an exergame-based training concept  (called ‘Brain-IT’) specifically for the secondary prevention of mild neurocognitive disorders (mNCD). The methodology followed the guidelines of the Medical Research Council for the development and evaluation of complex interventions and was closely aligned with the Multidisciplinary Iterative Design of Exergames (MIDE) - Framework. Primary end users (individuals with mNCD), secondary end users (physiotherapists, occupational therapists, healthcare professionals), exergaming researchers, as well as experts from the exergaming industry were continuously involved to facilitate the acceptance and transfer of the resulting training concept into clinical practice. 

Results: In the first phase of the project, we successfully determined a set of design requirements for the 'Brain-IT' training concept in collaboration with 10 experts and 8 individuals with mNCD. This set of design requirements formed the basis for phase 2, where a first prototype of the 'Brain-IT' training concept was co-designed and developed. We iteratively tested and refined this prototype until we achieved an "acceptable" (= feasible, usable, safe, and well accepted) solution. In the final randomized controlled trial (RCT), we observed statistically significant effects with large effect sizes for global cognitive performance, immediate verbal recall, and delayed verbal recall in favor of the intervention group. 55 % of participants showed a clinically relevant improvement in global cognitive functioning in response to training. The remaining (underpowered) statistical analyses revealed no significant effects, but favorable changes in descriptive statistics with small to moderate effects in favor of the intervention group, particularly with regards to quality of life. We also obtained data from a battery of structural and functional brain magnetic resonance imaging scans to explore possible neural changes in relation to cognitive performance adaptations. While the analyses of these data is ongoing, preliminary results suggest intervention-related effects on gray matter volumes of the hippocampus, thalamus, left prefrontal cortex, left anterior cingulate cortex, and white matter volumes of the anterior cingulate cortex.

Conclusion: Our rigorous methodological approach resulted in a user-centered, personalized, and highly innovative training concept. Notably, we revealed, to the best of our knowledge, as the first research team, that this novel intervention approach of combining exergame training with biofeedback-guided resonance breathing is not only safe, feasible, and highly accepted by individuals with mNCD, but also effectively impacts its primary target outcomes by improving global cognitive performance, learning and memory, and showing positive structural changes in the hippocampus and subregions of the central autonomous network. Confirmatory studies are warranted to (i) further investigate the near and far-transfer effects of the training, (ii) determine whether these improvements translate to affecting the rates of progression to or onset of dementia, and (iii) test the implementation of the training in clinical practice.