Exercise Increases Brain-Derived Neurotrophic Factor Levels in Older Adults to Improve Cognitive Function in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prominent form of dementia caused by aging (Choi et al., 2018). This disease negatively impacts the brain, causing cognitive deficits, degeneration of neurons, and brain inflammation. Alzheimer's patients have reduced brain-derived neurotrophic factor (BDNF) and other proteins that promote neuronal function. However, numerous studies have determined that physical exercise promotes neurotrophin levels and increases growth factors, including BDNF.

In 2014, Coelho et al. studied how acute aerobic exercise affects BDNF levels in older adults with AD. In this study, 21 older adults with AD and 18 older adults in the control group performed a treadmill walking exercise trial until the participant reached 85% of their maximum heart rate. Throughout the trial, blood samples were taken and analyzed for levels of BDNF. The exercise trial significantly increased BDNF plasma levels by 22% in AD participants and by 16% in control participants. Additionally, the study included a questionnaire about physical activity levels prior to the trial which revealed that individuals with a higher level of physical activity on a regular basis had higher BDNF levels. These results suggest an important role for physical exercise in elevating BDNF levels both in healthy older adults and older adults with AD.

Another study on exercise and BDNF was published in 2015 by Nascimento et al., which examined elderly participants with Mild Cognitive Impairment (MCI) who may have lower levels of BDNF. Elderly individuals with MCI have a slight cognitive decline but maintain the ability to perform their daily activities. However, they are at a greater risk of developing dementias including AD, which makes intervention strategies such as exercise particularly important. In this study, 24 elderly adults with MCI participated in a 16-week exercise program involving muscular resistance, aerobic fitness, and motor coordination/balance exercises. Blood samples were taken to compare their levels of peripheral BDNF before and after the trial, as well as to a control group of 21 elderly adults with MCI who did not participate in the exercise trial. Both the concentration of BDNF, and the cognitive function of the participants in the exercise group increased significantly after 16 weeks. This suggests that exercise can help restore cognitive function in elderly with MCI, further supporting the benefits of exercise for older adults at risk of developing AD.

A different study by Choi et al. (2018) focused on how BDNF can imitate the cognitive benefits experienced from exercise in AD mice. One manipulation in this study found that physical activity increased BDNF amounts in the hippocampus. Adult hippocampal neurogenesis (AHN) refers to the continual lifelong generation of new neurons, with this process being impaired before the development of AD. When conducting experiments on 5xFAD mice, a transgenic mouse model for AD, exercise in combination with increased AHN had beneficial results. Generally, physical activity is known to augment levels of growth factors and neurotrophins in the brain, decreasing neuroinflammation. Inducing AHN alone led to no effects in mice, but activating AHN with exercise increased BDNF levels. 

In conclusion, all three studies investigated similar questions on the topic of how exercise affects BDNF levels in the brain, and ultimately how these affect patients suffering from AD. All three articles support that BDNF levels increase with exercise, further resulting in other benefits such as increased cognitive function. The methods between Coelho et al. (2014) and Nascimento et al. (2015) studies are very similar, where both experiments involved patients running on a treadmill as a form of physical activity, and then blood samples were taken from the subjects to observe BDNF levels. The study conducted by Choi et al. (2018) involved different methods, where the researchers carried out genetic modifications in mice. The study by Choi et al. focused more on what manipulations can mimic the effects of exercise on AD (such as inducing AHN), instead of solely focusing on the effects of exercise. These studies shared the same goals of understanding this disease better and how the quality of life of those with AD can be improved. This research shows the promise of exercise to increase BDNF levels to help reduce the risk of developing AD and reduce cognitive decline.

References

Coelho, F. G. de M., Vital, T. M., Stein, A. M., Arantes, F. J., Rueda, A. V., Camarini, R., Teodorov, E., & Santos-Galduróz, R. F. (2014). Acute Aerobic Exercise Increases Brain-Derived Neurotrophic Factor Levels in Elderly with Alzheimer’s Disease. Journal of Alzheimer’s Disease, 39(2), 401–408. https://doi.org/10.3233/JAD-131073

Nascimento, C. M. C., Pereira, J. R., Pires de Andrade, L., Garuffi, M., Ayan, C., Kerr, D. S., Talib, L. L., Cominetti, M. R., & Stella, F. (2015). Physical Exercise Improves Peripheral BDNF Levels and Cognitive Functions in Mild Cognitive Impairment Elderly with Different BDNF Val66Met Genotypes. Journal of Alzheimer’s Disease, 43(1), 81–91. https://doi.org/10.3233/JAD-140576

Choi, S. H., Bylykbashi, E., Chatila, Z. K., Lee, S. W., Pulli, B., Clemenson, G. D., Kim, E., Rompala, A., Oram, M. K., Asselin, C., Aronson, J., Zhang, C., Miller, S. J., Lesinski, A., Chen, J. W., Kim, D. Y., van Praag, H., Spiegelman, B. M., Gage, F. H., & Tanzi, R. E. (2018). Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model. Science, 361(6406). https://doi.org/10.1126/science.aan8821