Regular physical activity is widely recognized for its positive effects on brain health and cognitive performance. One biological mechanism believed to contribute to these benefits involves a protein known as brain-derived neurotrophic factor (BDNF). This protein helps to grow, survive, and to maintain the working of the neurons in the brain. Studies have proposed that exercise has the ability to boost the level of BDNF that may improve learning, memory, and other cognitive functions. Nevertheless, the mechanism between exercise, BDNF production, and cognitive performance is complicated and even contradictory.
Earlier studies have demonstrated that individuals with higher levels of cardiovascular fitness generally exhibit greater circulating BDNF concentrations. Notably, research has identified a positive association between cardiovascular fitness, assessed through maximal oxygen uptake (VO₂max), and resting plasma BDNF levels. There was also a meta-analysis of the evidence that exercise performed over a minimum of six weeks would be able to raise resting plasma BDNF concentrations. Although a single workout can increase the levels of BDNF temporarily in the bloodstream. These increments are mainly higher in plasma BDNF (pBDNF) as compared to serum BDNF (sBDNF).
These two types of BDNF are not exactly the same in terms of studies, although they represent two distinct physiological processes. Plasma BDNF is instantly circulated and capable of passing through the blood-brain barrier and is therefore more readily available to the brain. Conversely, serum BDNF is platelet stored, and it is regarded as a sign of BDNF release at the level of transcription. Researchers suggest that circulating pBDNF concentrations may serve as an indicator of BDNF levels in the central nervous system.
Human and animal experiments have shown that exercise can cause an increase in the production of BDNF in the brain, in particular, in the hippocampus, which is closely associated with memory and learning. Although there is compelling evidence to indicate that exercise is associated with increased levels of BDNF and increased cognition, most studies have studied the two independently. A significant portion of the studies focus on memory improvements, with most conducted in elderly or clinical populations. Other studies have established relationships between physical exercise, the level of BDNF, and hippocampal size in the elderly. Other individuals have demonstrated that aerobic exercise is able to increase executive functions of attention, problem-solving, and cognitive flexibility and raise BDNF concentrations.
The relationship between changes in BDNF and improvements in cognitive performance remains unclear. Higher exercise intensity has been shown to increase post-exercise serum BDNF and improve Stroop task performance, but no direct correlation between the two changes was found, and similar results were observed with the Wisconsin Card Sorting Task.
In another study, young sedentary males who completed a three- to five-week aerobic training program exhibited increases in exercise-induced serum BDNF and improvements in episodic memory, although their Stroop task performance remained unchanged. Long-term findings are also mixed: one study reported that resting-state serum BDNF mediated improvements in task-switching among older adults after one year of exercise, but not among younger adults.
It is not quite clear how alterations in BDNF are related to the improvement of cognitive performance. The intensity of exercise was reported to increase post-exercise serum BDNF and increase Stroop task performance, with no direct relationship between the two effects, and this was also true of the Wisconsin Card Sorting Task. In a different study, young sedentary males who underwent a three to five-week aerobic exercise program had better exercise-induced serum BDNF performance as well as episodic memory, but no change in the Stroop task performance.
Long-term results are also inconclusive: one study indicated that resting-state serum BDNF mediated the positive effect of exercise on task-switching after a year in older adults, but not in younger adults. To explore this further, a 12-week aerobic cycling intervention was conducted on non-exercising adults aged 18 to 55 years, consisting of a light training phase (weeks 0–6) followed by a moderate-to-vigorous phase (weeks 6–12). Among 49 participants (enrolled), 23 filled in the entire dataset (intervention: 10, female = 2, age = 35 ± 14 years; control: 13, female = 5, age = 34 ± 16years). The intervention group had improved cardiovascular fitness, with high VO2max at week 12 compared to week 0 and 6, but body fat percentage, BMI, and resting BDNF remained unchanged.
An increase in serum BDNF after acute maximal exercise only happened after the 12-week program and was associated with an increase in fitness (R =.40, p=.05) and V̇O2max (R=.49, p=.03). Plasma BDNF dropped in the case of acute exercise in the control group and was independent of fitness. As a whole, the research concluded that a resting BDNF and cognitive performance had no significant effect, but an increase in fitness resulted in serum BDNF that was produced during exercise and correlated with changes in prefrontal cortex activity during an executive function task.
References: Ronca F, Xu C, Kong E et al., BDNF relates to prefrontal cortex activity in the context of physical exercise. Brain Research. 2026. doi:10.1016/j.brainres.2026.150253
