Aerobic Exercise Mediates Neuroplasticity Improving Spatial Memory/Delaying Neurodegeneration
Throughout the 2020s one quarter of our worldwide population will be 65 years and above. Nine out of ten over 60 years old have a cardiovascular risk factor. Two or more risk factors are associated with cognitive decline, including reduced memory function and increased risk of dementia (Bherer, 2015). Research by Erickson et al., (2011), demonstrates aerobic exercise in adults aged 50 to 80 can bring improved memory function via regeneration within the hippocampus. This research shows that it is possible to ameliorate cognitive decline in older populations by encouraging regular exercise.
The hippocampus is part of the Medial Temporal Lobes (MTL) and known to have pivotal involvement in memory. The MTL acts as a hub with a large ‘receptive field’ for synaptic interaction with neurons from sensory, emotional, motor, memory and higher reasoning regions of the brain. The MTL is thus well situated for input and output signals active in long-term memory (Baars, 2010). Viard et al., (2012), report studies demonstrating anterior hippocampal involvement with processing environmental context, novelty, arousal, emotion, reward and their effects on memory. Whereas the posterior hippocampus is considered to have a crucial role in encoding environmental location to support spatial navigation. Altogether, the hippocampus acts to facilitate spatial memory. Reduction in hippocampal volume is associated with compromised memory and higher probability of dementia. (Raz N, et al., 2005). Previous research shows increased hippocampal volume in adults correlates with higher fitness levels (Erickson K et al., 2009). Reduction in hippocampal volume is 1-2% annually after the age of 50 (Raz N, et al., 2005), increasing the risk of cognitive impairment with age.
Researchers have shown that the brain can maintain a remarkable level of plasticity, even in older, frail individuals (Byrne, 2020), helping to avoid or postpone cognitive decline. Brain plasticity outlines the brain's capacity to adapt in form and function throughout life. Neuroplasticity may be central to understanding memory function and of key importance in treatment of neurological disorders and mental diseases. Aerobic exercise has previously been shown to increase the volume of the pre-frontal and temporal brain regions via augmentation of neuroplasticity and reduce cognitive impairment (Erickson K et al, 2010). Neurotransmitters play a pivotal part in plasticity and re-generation such as Brain Derived Neurotrophic Factor (BDNF), considered to mediate neurogenesis and dendritic expansion.
Erickson et al. (2011), randomized 145 older adults to participate in weekly moderate intensity aerobic exercise or gentle stretching and muscle toning exercises for one year. Magnetic Resonance Imaging (MRI) was used to measure brain regions at baseline, six months and completion. Spatial memory was assessed using the Spatial Memory Paradigm and serum BDNF was measured.
Results showed 2.12% growth in the anterior left hippocampus and 1.97% growth in the anterior right hippocampus. The control group experienced 1.4% volumetric decrease consistent with previous literature on natural decline. Both groups showed an increase in spatial memory, yet higher levels of aerobic fitness at the start of the study correlated with improved spatial memory. Increased serum BDNF correlated with improved memory and increased hippocampal volume but was not significantly different when compared to the stretching group. However increased quantities of serum BDNF during the study was linked with greater hippocampal volume. Results showed aerobic exercise elicited increases were specifically related to alterations in anterior hippocampal volume. BDNF changes were not linked with improved memory function, which implies other potential factors mediating this response. Cognitive function is a highly complex system involving synaptic plasticity mediated by a myriad of neurotransmitters (Autio J et al, 2020), therefore focussing on BDNF alone does not allow for complete mechanistic representation.
The MR imaging utilised does not provide conclusive evidence of the underlying mechanisms leading to the volumetric increase. Furthermore, Yue et al, 2020, found that Tai Chi practice may improve memory via hippocampal neuroplasticity when examining changes in grey matter density (GMD). Further studies utilising functional MRI to study working memory and measuring GMD would provide expanded understanding.
MRI data showed that the aerobic exercise induced increased hippocampal volume was not noted uni-formally in comparison to other brain structures such as the thalamus and caudate nucleus. The researchers argue this selectivity implies there are specific molecular pathways impacted by aerobic exercise within certain brain structures. Exercise induced serum BDNF increase leading to cell proliferation or increased dendritic branching is a proposed explanation for the increased hippocampal volume. However, improved vascularisation, angiogenesis alongside neurogenesis (Pereira, 2007) may be additional factors accounting for the increase in volume observed. Furthermore, there are likely to be indirect effects impacting brain structure and memory from the exercise intervention for example via improved stress-axis functioning, improved sleep, dietary alterations and reduced risk of coronary heart diseases.
A met-analysis of 15 studies confirmed up to a 38% reduced risk of dementia in individuals vigorously exercising more than three times weekly (Sofi et al. 2011). Further studies are required to uncover how exercise may augment plasticity in associated improved memory function. Examining changes in synaptic inhibition, facilitation and epigenetic alterations via DNA-methylation patterning could allow for greater understanding. DNA-methylation is involved in the maintenance of long-term memories and mediates synaptic plasticity and cognitive function (Day & Sweatt, 2011). Further, it is important to investigate other adaptations that can be used in parallel to reduce cognitive decline, such as social interaction (Fuchs, 2014), cognitive training (Bherer, 2015) and sexual activity, (Wright et al., 2017) . Studies show that stress is a powerful neurogenesis inhibitor within the hippocampus (Paizanis et al., 2007), therefore managing stress, particularly chronic social stress (Fuchs E & Flügge, 2014) is crucial especially during current social-distancing circumstances.
The results from Erickson et al., (2011), indicate that aerobic exercise is neuro-enhancing improving cognition. Future studies utilising functional MRI, measuring grey-matter density and investigating additional neurotransmitter activity are needed to better understand what conditions encourage neuroplasticity to reduce age‐related cognitive decline and neurodegenerative diseases. A holistic approach incorporating other behaviour adaptations is likely to enhance improvements.
References:
Autio, J., Stenbäck, V., Gagnon, D. D., Leppäluoto, J., & Herzig, K. H. (2020). (Neuro) Peptides, Physical Activity, and Cognition. Journal of clinical medicine, 9(8), 2592. https://doi.org/10.3390/jcm9082592
Baars, Bernard J (2010). Cognition, brain, and consciousness: Introduction to Cognitive Neuroscience. 2nd ed. Academic Press. http://www.vlebooks.com/Vleweb/Product/Index/193802?page=0
Behrer L. (2015). Cognitive plasticity in older adults: effects of cognitive training and physical exercise. Annals of the New York Academy of Sciences. 1337(1), 1-6. https://nyaspubs-onlinelibrary-wiley-com.ezproxy.lib.gla.ac.uk/doi/full/10.1111/nyas.12682
Byrne J. (2020). Synaptic Plasticity. Neuroscience Online. Chapter 7. https://nba.uth.tmc.edu/neuroscience/s1/chapter07.html
Day, J. J., & Sweatt, J. D. (2011). Epigenetic mechanisms in cognition. Neuron. 70(5), 813–829. https://doi.org/10.1016/j.neuron.2011.10.017.
Erickson K, Prakash R, Voss M, Chaddock L, Hu L, Morris K, White S, Wójcicki T, McAuley E & Kramer A. (2009). Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 19:1030–1039. https://doi.org/10.1002/hipo.20547
Erickson K, Raji C, Lopez O, Becker J, Rosano C, Newman A, Gach H, Thompson P, Ho A & Kuller L. (2010) Physical activity predicts gray matter volume in late adulthood: The Cardiovascular Health Study. Neurology. 75:1415–1422. https://doi.org/10.1212/WNL.0b013e3181f88359.
Erickson K, Voss M, Prakash R, Basak C, Szabo A, Chaddock L, Kim J, Heo S, Alves H, White S, Wojcicki T, Mailey E, Vieira V, Martin S, Pence B, Woods J, McAuley E & Kramer A. (2011). Exercise training increases size of hippocampus and improves memory. PNAS. 108( 7), 3017–3022. https://doi.org/10.5214/ans.0972.7531.220209
Fuchs E & Flügge G (2014). Adult Neuroplasticity: More Than 40 Years of Research. Neural Plasticity. Article ID 541870. 10 pages. https://doi.org/10.1155/2014/541870
Garthe A, Roeder I & Kempermann G (2016). Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis. Hippocampus. 26(2), pp. 261-271,
https://doi.org/10.1002/hipo.22520
Grady C. (2012). The cognitive neuroscience of ageing. Nat Rev Neurosci. 13(7):491-505. https://doi.org/10.1038/nrn3256
Kim, J. I., Lee J. W., Lee Y. A., Lee D. H., Han N. S., Choi Y. K., Hwang B. R., Kim H. J., Han J. S. (2013). Sexual activity counteracts the suppressive effects of chronic stress on adult hippocampal neurogenesis and recognition memory. Brain Research. 1538 (2013), pp 26-40. https://doi.org/10.1016/j.brainres.2013.09.2007
Lain A, Lieberman A, Pfannl R & Hedley-Whyte E (2010). Nodular Bilateral Amygdala Degeneration in Demented Individuals. Acta Neuropathologica. 120, 683–688. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057016/
Paizanis, E., Kelaï, S., Renoir, T. et al. Life-Long Hippocampal Neurogenesis: Environmental, Pharmacological and Neurochemical Modulations. Neurochem Res 32, 1762–1771 (2007). https://doi.org/10.1007/s11064-007-9330-0
Pereira A, Huddleston D, Brickman A, Sosunov A, Hen R, McKhann G, Sloan R, Gage F, Brown T, Small S (2007). An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proceedings of the National Academy of Sciences, 104 (13) 5638-5643. https://doi.org/10.1073/pnas.0611721104
Raz N, Lindenberger U, Rodrigue K, Kennedy K, Head D, Williamson A, Dahle C, Gerstorf D & Acker J (2005). Regional brain changes in aging healthy adults: General trends, individual differences and modifiers. Cereb Cortex. 15:1676–1689. https://doi.org/10.1093/cercor/bhi044
Sofi F, Valecchi D, Bacci D, Abbate R, Gensini G, Casini A, Macchi C. Physicial activity and risk of cognitive decline: a meta-analysis of prospective studies (2011). J. Int. Med. 169: 107-117. https://doi.org/10.1111/j.1365-2796.2010.02281.x
Viard A, Desgranges B, Eustache F, Piolino P (2012). Factors affecting medial temporal lobe engagement for past and future episodic events: An ALE meta-analysis of neuroimaging studies. Brain and Cognition. 80(1), pp 111-125. https://doi.org/10.1016/j.bandc.2012.05.004.
Weaver I.(2020). Epigenetics in Psychology. https://nobaproject.com/modules/epigenetics-in-psychology
Wright, H., Jenks R. A., Demeyere N. (2017). Frequent sexual activity predicts specific cognitive abilities in older adults. J. Gerontol. Series B, 74 (1), 47-51. https://doi.org/10.1093/geronb/gbx065
Yue, C., Yu, Q., Zhang, Y., Herold, F., Mei, J., Kong, Z., Perrey, S., Liu, J., Müller, N. G., Zhang, Z., Tao, Y., Kramer, A., Becker, B., & Zou, L. (2020). Regular Tai Chi Practice Is Associated With Improved Memory as Well as Structural and Functional Alterations of the Hippocampus in the Elderly. Frontiers in aging neuroscience, 12, 586770. https://doi.org/10.3389/fnagi.2020.586770