Physical exercise increases peripheral brain-derived neurotrophic factors in patients with cognitive impairment: A meta-analysis

Background: Physical exercise can improve cognitive dysfunction. Its specific mechanism remains unknown. Recent studies have indicated that elevating or peripherally overexpressing brain-derived neurotrophic factors (BDNF) improve cognitive impairment. Objective: This meta-analysis aimed to investigate whether physical exercise improves cognitive performance in patients with cognitive dysfunction, such as mild cognitive impairment (MCI) or Alzheimer’s disease (AD), by increasing peripheral BDNF. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to June 2020 for studies that assayed the changes in peripheral BDNF levels in MCI and AD patients after exercise training. Results: Peripheral BDNF levels were significantly elevated after a single exercise session (SMD = 0.469, 95% CI: 0.150–0.787, P = 0.004) or regular exercise interventions (SMD = 0.418, 95% CI: 0.105–0.731, P = 0.009). Subgroup analysis showed that only regular aerobic exercise interventions (SMD = 0.543, 95% CI: 0.038–1.049, P = 0.035) and intervention duration of 16 weeks or greater (SMD = 0.443, 95% CI: 0.154 –0.733, P = 0.003) significantly increased peripheral BDNF levels. Only plasma BDNF levels (SMD = 0.365, 95% CI:0.066–0.664, P = 0.017) were significantly increased after exercise interventions. Conclusions: Acute and chronic physical exercises may improve cognitive impairment by increasing peripheral BDNF levels. Aerobic exercises and a longer duration of exercising increased BDNF levels. These findings also suggest that BDNF may be a suitable biomarker for evaluating the effect of exercise in patients with cognitive impairment, such as AD or MCI.