Exercise-induced brain-derived neurotrophic factor expression: Therapeutic implications for Alzheimer's dementia.

Emerging evidence indicates that moderate intensity aerobic exercise is positively correlated with cognitive function and memory. However, the exact mechanisms underlying such improvements remain unclear. Recent research in animal models allows proposition of a pathway in which brain-derived neurotrophic factor (BDNF) is a key mediator. This perspective draws upon evidence from animal and human studies to highlight such a mechanism whereby exercise drives synthesis and accumulation of neuroactive metabolites such as myokines and ketone bodies in the periphery and in the hippocampus to enhance BDNF expression. BDNF is a neurotrophin with well-established properties of promoting neuronal survival and synaptic integrity, while its influence on energy transduction may provide the crucial link between inherent vascular and metabolic benefits of exercise with enhanced brain function. Indeed, BDNF mRNA and protein is robustly elevated in rats following periods of voluntary exercise. This was also correlated with improved spatial memory, while such benefits were abolished upon inhibition of BDNF signaling. Similarly, both BDNF and cardiovascular fitness arising from aerobic exercise have been positively associated with hippocampal volume and function in humans. We postulate that exercise will attenuate cortical atrophy and synaptic loss inherent to neurodegenerative disorders - many of which also exhibit aberrant down-regulation of BDNF. Thus, the proposed link between BDNF, exercise and cognition may have critical therapeutic implications for the prevention and amelioration of memory loss and cognitive impairment in Alzheimer's disease and associated dementias.