The Importance of Resistance Training Volume and Its Relationship with Cognitive Function and Brain Structure in Individuals with Cognitive Impairment. The Exercise4Brain Study

The Exercise4Brain study is a randomized controlled trial that aims to compare the effects of different resistance training volume configurations on cognitive function and brain structure in cognitively impaired individuals. Furthermore, it aims to analyze the impact of detraining followed by a retraining period on cognitive function and brain structure in cognitively impaired individuals. Specifically, the analyses of cognitive functions will encompass domains such as attention and concentration, executive functions, memory, language, visuospatial skills, conceptual thinking, calculations, and orientation. On the other hand, regional macrostructural brain measures, particularly hippocampal, corpus callosum, and total brain volume, will be the primary focus , due to their strong relationship with cognitive decline and neurodegeneration. This randomized controlled trial will address a research gap in the scientific literature and provide important insights into the resistance training volume (dose) required to preserve or improve cognitive function and to induce favorable structural brain changes in cognitively impaired individuals. Furthermore, as no study has explored the effects of different resistance training volumes followed by detraining and retraining on these outcomes, the Exercise4Brain study aims to present novel practical applications and guidelines for clinicians, exercise physiologists, and researchers on the most efficient approach to prescribing and manipulating training volume over time. In addition to the primary aims, the Exercise4Brain study establishes secondary aims, including analyzing the effects of different resistance training volume configurations on additional macrostructural brain measures (cortical thickness, prefrontal cortical volume, gray and white matter volumes), microstructural white matter integrity and connectivity (assessed via fractional anisotropy and mean, radial and axial diffusivities), and serum neurofilament light chain and brain-derived neurotrophic factor (all biomarkers associated with neuronal integrity and cognitive function). Furthermore, other cognitive domains of executive and attentional processes will be analyzed, including inhibitory control, cognitive initiation, and verbal fluency, as well as memory domains such as short-term memory, working memory, and episodic verbal memory. Biomarkers of oxidative stress, immunological response, liver function, and muscle function will also be analyzed to address the intervention effects on these specific outcomes. Finally, we will explore the impact of the interventions on hemodynamic responses, glycemic status, lipid profile, and physical performance. The aims described here have never been analyzed in any randomized controlled trial among cognitively impaired individuals. Additionally, the interdisciplinary approach demonstrates a novel integration of concepts and approaches from different disciplines (i.e., Sport Sciences, Medicine, and Psychology). Overall, this represents a solid opportunity to advance knowledge in cognitive health and exercise science through innovative approaches that could positively impact academic, scientific, and civil society communities.