The Role of Exercise in Alzheimer’s Disease Treatment and Prevention

by Zaid Firas, March 2025

As Alzheimer’s disease (AD) continues to affect millions worldwide, scientists are uncovering a powerful new ally in the fight against cognitive decline: exercise. But how exactly does staying active impact your brain health, and what evidence exists to support this?

Currently, treatments for AD include acetylcholinesterase inhibitors (AChEIs) as well as antagonists to N-methyl D-aspartate (NMDA). AChEIs work by preventing the breakdown of acetylcholine, a neurotransmitter crucial for cognitive function. By increasing acetylcholine levels in the brain, this inhibitor helps improve memory and cognitive symptoms in mild to moderate AD (1). However, their efficacy is limited, and they do not halt disease progression. NMDA antagonists help regulate glutamate activity. In AD, excessive glutamate can lead to neuronal damage. These antagonists block NMDA receptors to reduce this overactivation while still allowing normal synaptic transmission, leading to modest improvements in cognition and daily function in moderate to severe AD (2). However, these approved drugs are only effective in treating the symptoms of AD but are unable to cure or prevent the disease (3). This creates a demand for research in the area of AD prevention and curative treatment. Although there is no cure for AD yet, there is promising research providing evidence that exercise can improve learning and memory as well as attenuate AD (4). 

Physical activity has long shaped our physiology, which is not surprising considering that the ability of our species to survive in many different environments, escape predators, and look for food depends on physical activity (5). As you exercise, your heart increases the amount of blood flow to the rest of the body. This increase in circulation subsequently increases cerebral blood flow, which is linked to heightened neural activity (6). Furthermore, exercise increases different trophic factors that are key in regulating the maintenance, growth and even survival of neurons (7). One of these trophic factors is known as the brain-derived neurotrophic factor (BDNF) and is highly concentrated in the hippocampus (a brain region important for memory consolidation) (8). Decreased levels of BDNF are usually associated with age-related memory impairment, but it seems that exercise can ameliorate deterioration and even improve memory function (9). 

As Alzheimer’s disease (AD) continues to affect millions worldwide, scientists are uncovering a powerful new ally in the fight against cognitive decline: exercise. But how exactly does staying active impact your brain health, and what evidence exists to support this?

Currently, treatments for AD include acetylcholinesterase inhibitors (AChEIs) as well as antagonists to N-methyl D-aspartate (NMDA). AChEIs work by preventing the breakdown of acetylcholine, a neurotransmitter crucial for cognitive function. By increasing acetylcholine levels in the brain, this inhibitor helps improve memory and cognitive symptoms in mild to moderate AD (1). However, their efficacy is limited, and they do not halt disease progression. NMDA antagonists help regulate glutamate activity. In AD, excessive glutamate can lead to neuronal damage. These antagonists block NMDA receptors to reduce this overactivation while still allowing normal synaptic transmission, leading to modest improvements in cognition and daily function in moderate to severe AD (2). However, these approved drugs are only effective in treating the symptoms of AD but are unable to cure or prevent the disease (3). This creates a demand for research in the area of AD prevention and curative treatment. Although there is no cure for AD yet, there is promising research providing evidence that exercise can improve learning and memory as well as attenuate AD (4). 

Physical activity has long shaped our physiology, which is not surprising considering that the ability of our species to survive in many different environments, escape predators, and look for food depends on physical activity (5). As you exercise, your heart increases the amount of blood flow to the rest of the body. This increase in circulation subsequently increases cerebral blood flow, which is linked to heightened neural activity (6). Furthermore, exercise increases different trophic factors that are key in regulating the maintenance, growth and even survival of neurons (7). One of these trophic factors is known as the brain-derived neurotrophic factor (BDNF) and is highly concentrated in the hippocampus (a brain region important for memory consolidation) (8). Decreased levels of BDNF are usually associated with age-related memory impairment, but it seems that exercise can ameliorate deterioration and even improve memory function (9). 

Figure 1: How exercise may protect against AD. Regular physical activity boosts brain-derived neurotrophic factor (BDNF) and improves vascular health, promoting neurogenesis, stronger synaptic connections, and better brain network functions. These effects contribute to enhanced brain health, greater cognitive reserve and a reduced risk of AD (10).

Research suggests that the environment in which exercise is performed may be just as important as the exercise itself in increasing cognitive function. Exercise improves cognition, and so does time spent in natural outdoor environments, which has led researchers to believe that a combination of both will maximize cognitive increase (11). One study showed that walking outdoors for 15 minutes demonstrated improved performance and an increase in the neural response commonly associated with working memory. Conversely, this result was not seen following a 15-minute walk inside (11). Many studies have linked the cognitive improvements following exercise to the increased capacity of the heart, as well as the release of neurotrophic factors, as previously mentioned As a result, it is difficult to assess what the ideal exercise is for brain health, causing the topic to still be under debate (12). 

Exercise not only slows down the progression of dementia, but it can also prevent it’s onset as well. Individuals who engage in consistent exercise may be up to 20% less likely to develop dementia compared to those who are inactive (13). Additionally, a study found that people over 60 who are at high risk of AD  had a lower risk of developing the disease if they performed 30 minutes of moderate exercise five days a week (14). These findings highlight the critical role of physical activity in reducing AD risk, emphasizing that even moderate exercise can be a simple yet effective way to support long-term brain health. 

AD treatment and prevention remains a major area of research demand, however, there is substantial evidence supporting exercise as one of the most powerful tools in protecting brain health. Whether through a brisk walk, strength training, or yoga, regular movement can help lower your risk, improve cognitive function, and support overall well-being. If you have a loved one at risk for AD, consider encouraging them to stay active as well. Your future self depends on the choices you make today. Prioritize movement, protect your mind, and make exercise a lifelong habit. 

While the benefits of exercise for brain health are well-documented, many questions remain unanswered. Future research should focus on identifying the most effective types, intensities, and durations of exercise for preventing or slowing AD. Longitudinal studies that track individuals over decades could provide more definitive evidence on the long-term cognitive benefits of different exercise regimens. As research advances, integrating exercise-based interventions with pharmacological treatments may offer a more comprehensive strategy for combating AD. 

References 

1. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. The Cochrane database of systematic reviews [Internet]. 2006;1(1):CD005593. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005593/full

2. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ. Memantine in Moderate-to-Severe Alzheimer’s Disease. New England Journal of Medicine [Internet]. 2003 Apr 3;348(14):1333–41. Available from: https://pubmed.ncbi.nlm.nih.gov/12672860/

3. Yiannopoulou KG, Papageorgiou SG. Current and Future Treatments for Alzheimer’s Disease. Therapeutic Advances in Neurological Disorders [Internet]. 2012 Oct 15;6(1):19–33. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526946/

4. Lin TW, Tsai SF, Kuo YM. Physical exercise enhances neuroplasticity and delays alzheimer’s disease. van Praag H, editor. Brain Plasticity [Internet]. 2018 Dec 12;4(1):95–110. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296269/

5. Neufer P  Darrell, Bamman Marcas M, Muoio Deborah M, Bouchard C, Cooper Dan M, Goodpaster Bret H, et al. Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits. Cell Metabolism. 2015 Jul;22(1):4–11.

6. Shetty M. The Impact of Exercise on Brain Health and Preservation | Cognitive Enhancement [Internet]. Lifestyle Medicine. 2023. Available from: https://longevity.stanford.edu/lifestyle/2023/11/29/the-impact-of-physical-exercise-on-brain-health-and-preservation/

7. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, et al. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Experimental Physiology. 2009 Sep 15;94(10):1062–9.

8. Cowansage K, LeDoux J, Monfils Marie-H. Brain-Derived Neurotrophic Factor: A Dynamic Gatekeeper of Neural Plasticity. Current Molecular Pharmacology. 2010 Jan 1;3(1):12–29.

9. Maass A, Düzel S, Brigadski T, Goerke M, Becke A, Sobieray U, et al. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. NeuroImage [Internet]. 2016 May 1 [cited 2021 Oct 10];131:142–54. Available from: https://pubmed.ncbi.nlm.nih.gov/26545456/

10. Spires-Jones TL, Ritchie CW. A brain boost to fight Alzheimer’s disease. Science. 2018 Sep 6;361(6406):975–6.

11. Boere K, Lloyd K, Binsted G, Krigolson OE. Exercising is good for the brain but exercising outside is potentially better. Scientific Reports [Internet]. 2023 Jan 20;13(1):1140. Available from: https://www.nature.com/articles/s41598-022-26093-2

12. Gomes-Osman J. What kinds of exercise are good for brain health? - Harvard Health Blog [Internet]. Harvard Health Blog. 2018. Available from: https://www.health.harvard.edu/blog/what-kinds-of-exercise-are-good-for-brain-health-2018050213762

13. Physical activity and the risk of dementia [Internet]. Alzheimer’s Society. 2024 [cited 2025 Mar 12]. Available from: https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/reduce-your-risk-of-dementia/physical-activity?utm_source=chatgpt.com

14. A Mental Workout [Internet]. Alzheimer’s Disease and Dementia. 2020. Available from: https://www.alz.org/news/2020/a-mental-workout