Heisz J, Clark I, Bonin K, et al. The effects of physical exercise and cognitive training on memory and neurotrophic factors. J Cogn Neurosci. 2017;29(11):1895-1907.
To examine the impact of exercise training vs combined exercise and cognitive training to determine whether there are synergistic effects on memory in humans. Neurotrophic factors that support the survival and function of hippocampal cells were also measured to surmise possible mechanisms for any observed memory changes.
Nonrandomized intervention study
Ninety-five healthy young adults aged 17 to 30 years (58 women, 37 men) who engaged in less than or equal to 1 hour per week of vigorous exercise at baseline
Participants completed 6 weeks of either exercise training, combined exercise aand cognitive training, or no training (control). Exercise training consisted of 20 minutes of high-intensity interval training approximately 3 times a week for 6 weeks (mean number of training sessions for the exercise group: 17 ± 1 SD). Cognitive training consisted of 20 minutes of training on a computerized version of the Concentration Memory Task approximately 3 times a week for 6 weeks.
Study Parameters Assessed
- Peak oxygen consumption (VO2 peak) to prove that exercise training improved aerobic fitness 12-hour fasting blood samples to measure serum brain-derived neurotrophic factor (BDNF) and serum insulin-like growth factor-1 (IGF-1)
- Kirwan and Stark’s Mnemonic Similarity Task (MST) to test memory function. The MST tests memory of images of everyday objects, specifically high-interference memory and general recognition. High interference memory was defined as bias-corrected ability to correctly identify lure items as “similar” and general recognition was defined as bias-corrected ability to correctly identify a repetition as “old.”
Primary Outcome Measures
- Peak oxygen consumption at the end of the 6-week exercise intervention; participants with VO2 peak >4.6mL/kg/min were considered high-responders and those with VO2 peak <4.6 mL/kg/min were considered low-responders.
- Improvement in high-interference and general recognition memory tasks from baseline to end of 6-week exercise intervention
- Change in serum levels of BDNF and IGF-1 from baseline to end of 6-week intervention
- Both the exercise-only and combined exercise and cognitive training groups had better high-interference memory performance than the control group (P<0.05).
- Serum BDNF and IGF-1 levels increased significantly from baseline in individuals who exhibited a larger aerobic adaptation to exercise training (ie, high-responders; P<0.05).
- High-responders to exercise who also received cognitive training had better high-interference memory performance than those in the exercise-only group (P=0.037).
Physical activity is associated with improvements in cognitive function in both animal and human models. In humans, an active lifestyle and cardiovascular fitness are associated with better cognitive function during aging.1 Other cross-sectional studies have found that aerobic fitness predicts better memory performance on tasks of delayed free recall,2 relational memory,3 and spatial learning.4
However, few studies have examined the combined effects of exercise and cognitive training in humans, and these have been limited to older adult populations.5,6
Perhaps the question at hand, regarding exercise, should be, “What type, intensity, and frequency is ideal for improving memory?"
Animal models have found that exercise promotes the proliferation of new neurons within the dentate gyrus of the hippocampus, while cognitive training promotes survival and integration of those new neurons within the network. The hippocampus is associated mainly with memory, in particular the formation and retrieval of memories for complex events and episodes.7 In contrast, the dentate gyrus is related to the finer details of memory; specifically, it plays an important role in resolving interference between highly similar contexts.
This study examines the impact of exercise training vs combined exercise and cognitive training to determine whether there are synergistic effects on memory in young adults. This study also assessed the impact of training on aerobic fitness and the serum neurotrophic factors BDNF and IGF-1.
Studies have shown that associations between higher aerobic fitness and better memory performance may be enhanced by increases in neurotrophic factors. IGF-1 and BDNF are both known to influence neurogenesis and plasticity through similar signaling pathways.8 Brain-derived neurotrophic factor helps the brain to develop new connections, repair failing brain cells, and protect healthy brain cells. It has also been proven to regulate synaptic plasticity, which is essential for high interference memory.9 Additionally, IGF-1—a known potent stimulus for angiogenesis—is increased by exercise, and is believed to act as an upstream mediator to increase the production of BDNF in the hippocampus.7
The authors found that high-responders to exercise in the combined training group had better high-interference memory performance than high-responders to exercise who only received exercise training. In addition, high-responders also had higher levels of BDNF and IGF-1. Thus, the authors suggest that additional memory benefit from cognitive training may require the availability of neurotrophic factors. However, this should be interpreted with caution. It was noted in the study that serum levels of neurotrophic factors BDNF and IGF-1 were not impacted by exercise or combined interventions at the group level. This is contrary to data in previous animal models.10-12
These findings do suggest that the potential for synergistic effects of combining exercise and cognitive training may depend on aerobic fitness gains and the availability to produce neurotrophic factors.
Although this study highlights the importance of aerobic fitness adaptations, this is only one of the many different physiologic adaptations that take place during exercise training that could contribute to the effects on memory. Perhaps the question at hand, regarding exercise, should be, “What type, intensity, and frequency is ideal for improving memory?" This study also suggests that the potential for synergistic effects of combining exercise and cognitive training may depend on individual differences, in particular, the ability to produce neurotrophic factors.
- Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci USA. 2004;101(9):3316-3321.
- Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc of the Natl Acad of Sci USA. 2007;104(13):5638-5643.
- Monti JM, Hillman CH, Cohen NJ. Aerobic fitness enhances relational memory in preadolescent children: the FITKids randomized control trial. Hippocampus. 2012;22(9):1876-1882.
- Holzschneider K, Wolbers T, Röder B, Hötting K. Cardiovascular fitness modulates brain activation associated with spatial learning. Neuroimage. 2012;59(3):3003-3014.
- Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263.
- Law LL, Barnett F, Yau MK, Gray MA. Effects of combined cognitive and exercise interventions on cognition in older adults with and without cognitive impairment: a systematic review. Ageing Res Rev. 2014:15:61-75.
- Olsen RK, Moses SN, Riggs L, Ryan JD. The hippocampus supports multiple cognitive processes through relational binding and comparison. Front Hum Neurosci. 2012;6:146.
- Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-472.
- [Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004;20(10):2580-2590.
- Ding Y, Li J, Luan X, et al. Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience. 2004;124(3):583-591.
- Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996;726(1-2):49-56.
- Rasmussen P, Brassard P, Adser H, et al. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol. 2009;94(10):1062-1069.