Effects of exercise on brain-derived neurotrophic factor in Alzheimer's disease models: A systematic review and meta-analysis

A growing body of research examining effects of exercise on brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) models, while due to differences in gender, age, disease severity, brain regions examined, and type of exercise intervention, findings of available studies were conflicting. In this study, we aimed to evaluate current evidence regarding effects of exercise on BDNF in AD models. Searches were performed in PubMed, Web of Science, Cochrane, and EBSCO electronic databases, through July 20, 2023. We included studies that satisfied the following criteria: eligible studies should (1) report evidence on experimental work with AD models; (2) include an exercise group and a control group (sedentary); (3) use BDNF as the outcome indicator; and (4) be randomized controlled trials (RCTs). From 1196 search records initially identified, 36 studies met the inclusion criteria. There was a significant effect of exercise on increasing BDNF levels in AD models [standardized mean differences (SMD) = 0.98, P < 0.00001]. Subgroup analysis showed that treadmill exercise (SMD = 0.92, P< 0.0001), swimming (SMD = 1.79, P< 0.0001), and voluntary wheel running (SMD = 0.51, P= 0.04) were all effective in increasing BDNF levels in AD models. In addition, exercise significantly increased BDNF levels in the hippocampus (SMD = 0.92, P< 0.00001) and cortex (SMD = 1.56, P= 0.02) of AD models. Exercise, especially treadmill exercise, swimming, and voluntary wheel running, significantly increased BDNF levels in hippocampus and cortex of AD models, with swimming being the most effective intervention type.