Benefits of exercise in Alzheimer’s disease

By Sarah Choi

With lockdown, quarantine, and the pandemic having continued for more than a year, many have been unable to go to the gym, and have had much less opportunity for physical activity. However, while people may be spending an unprecedented amount of time indoors nowadays, the popularisation of exercising at home has provided an alternative way to maintain a healthy lifestyle. Whether it is running, hiking, or exercising at home, it may be encouraging to know that physical activity also has markedly beneficial effects on the biology of the brain. In particular, exercising has preventive and ameliorative effects on neurodegenerative diseases.

While it is commonly known that exercise improves physical fitness, it also makes changes to the chemicals in the brain. Exercise is used as treatment for neurological diseases, in addition to others such as psychiatric diseases and cardiopulmonary diseases (Pedersen and Saltin, 2015). One of these neurological diseases is Alzheimer’s disease (AD). A common cause of dementia, AD is a neurodegenerative disease characterised by the loss of neural connections and neurotransmitters. Along with the iconic amyloid plaques and tangles, patients with AD also see a decrease in neurotrophic factors, implicated in growth of nervous tissue. Exercise, as it turns out, can regulate and increase these neurotrophic factors, which has been shown to protect adults against AD (Ng et al., 2019), pointing to therapeutic effects for patients.

Exercise has been found to have neuroadaptive and neuroprotective effects via the increased gene expression of neurotrophic factors such as the brain-derived neurotrophic factor (BDNF). BDNF contributes to neuronal survival, differentiation, and plasticity. This growth factor has been found in many brain areas, with especially high levels in the hippocampus, a region associated with learning and memory. A possible pathway for increasing BDNF expression may be the PGC-1α/FNDC5 pathway. A study has shown that exercise induces fibronectin type III domain-containing protein 5 (FNDC5), which is then processed and secreted as irisin, a protein that is also lacking in Alzheimer’s disease. FNDC5 expression is regulated and activated by PARγ coactivator-1 α (PGC-1α), and reduced expression is seen in PGC-1α knockout mice. It has also been shown that levels of FNDC5 are proportional to BDNF levels. For example, artificially increasing levels of FNDC5 then increases BDNF expression (Wrann et al., 2013). Therefore, through the increase in FNDC5 expression, exercise can elevate BDNF expression, providing neuroprotective results.

Physical exercise has also been found to have other favourable effects on the brain. More and more studies have supported the preventive value of exercise in Alzheimer’s disease. Regular exercise can improve redox homeostasis in the brain, which also reduces amyloid-β aggregation. It has been shown that muscular contraction induces reactive oxygen species (ROS) generation while also reducing oxidative damage markers and increasing antioxidant and anti-inflammatory pathways. This helps with neuronal stem cell differentiation, contributing to neurogenesis. As BDNF regulation also involves redox-dependent pathways, and PGC-1α is involved in energy metabolism, this also helps increase BDNF levels. Furthermore, BDNF acts alongside insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and other growth factors to mediate neurogenerative and neuroprotective effects (Quan et al., 2020). Exercise also increases levels of neurotrophic factors through boosting levels of metabolic factors such as ketone bodies and lactate, and muscle-derived myokines such as cathepsin-B (Valenzuela et al., 2020). Clearly, the pathways and effects of physical exercise have numerous and notable beneficial effects on the healthy brain, as well as on the brains of AD patients.

Overall, exercise increases neurotrophic factors and induces many pathways that can decrease the risks of neurodegenerative diseases. The importance of regular physical exercise is once again highlighted through its neurogenerative and neuroprotective benefits.

References:

Ng, T. K. S. et al. (2019) ‘Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): A systematic review and meta-analysis’, International Journal of Molecular Sciences. MDPI AG. doi: 10.3390/ijms20020257.

Pedersen, B. K. and Saltin, B. (2015) ‘Exercise as medicine – Evidence for prescribing exercise as therapy in 26 different chronic diseases’, Scandinavian Journal of Medicine and Science in Sports. doi: 10.1111/sms.12581.

Quan, H. et al. (2020) ‘Exercise, redox system and neurodegenerative diseases’, Biochimica et Biophysica Acta – Molecular Basis of Disease. Elsevier B.V., p. 165778. doi: 10.1016/j.bbadis.2020.165778.

Valenzuela, P. L. et al. (2020) ‘Exercise benefits on Alzheimer’s disease: State-of-the-science’, Ageing Research Reviews. Elsevier Ireland Ltd. doi: 10.1016/j.arr.2020.101108.

Wrann, C. D. et al. (2013) ‘Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway’, Cell Metabolism. doi: 10.1016/j.cmet.2013.09.008.

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