Effects of physical exercise on plasma brain-derived neurotrophic factor in neurodegenerative disorders: A systematic review and meta-analysis of randomized controlled trials

Neurodegenerative disorders are associated with reduced levels of brain-derived neurotrophic factor (BDNF). We aimed to assess the effect of exercise interventions on plasma BDNF levels in individuals with neurodegenerative disorders. Eighteen randomized controlled trials (RCT) assessing the effects of exercise interventions versus no exercise on plasma BDNF levels in individuals with neurodegenerative disorders (i.e., multiple sclerosis, Parkinson's disease, mild cognitive impairment [MCI] and Alzheimer's disease) were included. Overall, exercise interventions induced a significant increase in plasma BDNF levels (SMD=2.22, 95% CI=1.33-3.12, p<0.001; 18 studies), which was separately confirmed for multiple sclerosis (SMD= 2.40, 95% CI= 1.30-3.50, p<0.001; 10 studies) and Parkinson's disease (SMD= 10.00, 95% CI= 2.48-17.51, p=0.009; 3 studies), with a non-significant trend also observed for MCI (SMD= 1.07, 95% CI= -0.14-2.28, p=0.080; 4 studies). BDNF levels significantly increased regardless of exercise type (p<0.001, p=0.003 and p=0.020 for combined, aerobic and resistance exercise, respectively), weekly exercise volume (p<0.001 for both >150 and <150 min/week) and intervention length (p<0.001 for both interventions of >12 and <12 weeks). In conclusion, physical exercise interventions increase plasma BDNF levels in individuals with neurodegenerative disorders. PROSPERO registration number: CRD42020199459.