Physical activity for cognitive health promotion: An overview of the underlying neurobiological mechanisms

Physical activity is one of the modifiable factors of cognitive decline and dementia with the strongest evidence. Although many influential reviews have illustrated the neurobiological mechanisms of the cognitive benefits of physical activity, none of them have linked the neurobiological mechanisms to normal exercise physiology to help the readers gain a more advanced, comprehensive understanding of the phenomenon. In this review, we address this issue and provide a synthesis of the literature by focusing on five most studied neurobiological mechanisms. We show that the body's adaptations to enhance exercise performance also benefit the brain and contribute to improved cognition. Specifically, these adaptations include, 1), the release of growth factors that are essential for the development and growth of neurons and for neurogenesis and angiogenesis, 2), the production of lactate that provides energy to the brain and is involved in the synthesis of glutamate and the maintenance of long-term potentiation, 3), the release of anti-inflammatory cytokines that reduce neuroinflammation, 4), the increase in mitochondrial biogenesis and antioxidant enzyme activity that reduce oxidative stress, and 5), the release of neurotransmitters such as dopamine and 5-HT that regulate neurogenesis and modulate cognition. We also discussed several issues relevant for prescribing physical activity, including what intensity and mode of physical activity brings the most cognitive benefits, based on their influence on the above five neurobiological mechanisms. We hope this review helps readers gain a general understanding of the state-of-the-art knowledge on the neurobiological mechanisms of the cognitive benefits of physical activity and guide them in designing new studies to further advance the field.