Evaluating exercise-induced changes in BDNF and cognitive development in children and adolescents: A multi-pathway operationalized framework

Brain-Derived Neurotrophic Factor (BDNF) supports synaptic plasticity, neurogenesis, and cognitive function, with higher levels often linked to improved memory and neural health. Exercise has gained attention as a practical approach to modulating BDNF and enhancing cognitive health in children and adolescents. However, this relationship is complex, non-linear, and often not explained by a single causal pathway. This review proposes that BDNF is sufficient but not necessary for cognitive improvements, since multiple parallel biological mechanisms can independently support learning and memory. Improvements in cognitive processes from exercise are not always proportional to changes in circulating BDNF; instead, other BDNF-independent mechanisms, such as lactate signaling, cerebral blood flow, neurotransmitter modulation, endocannabinoid activity, and anti-inflammatory effects, may also contribute to modulate cognitive function. These variables raise important questions about the consistency of exercise-induced BDNF changes and their translation into meaningful cognitive improvements, particularly in areas like memory and executive function. This framework helps explain inconsistencies in the literature and highlights the need for a more integrative mechanistic understanding of how exercise influences cognition. This review develops a multi-pathway operationalized model linking exercise to cognition, incorporating measurable biomarkers and generating falsifiable predictions across acute and chronic exercise conditions. Evidence on the effects of exercise on BDNF and cognition in children and adolescents is synthesized to evaluate whether exercise-induced BDNF changes translate into meaningful cognitive improvements, while identifying key research gaps and directions for future research within a multi-pathway framework.These findings also support a future framework in which exercise prescriptions may be mechanistically tailored to selectively recruit pathways such as BDNF signaling for targeted modulation of specific cognitive domains and temporal cognitive objectives.