Alzheimer’s & Exercise
Our bodies were designed to be moved, but due to our modern lifestyles, being sedentary is the norm. What once was a way of life - scavenging for food and manual occupations - now to many is an inconvenience that can be bypassed with a car or an Uber Eats delivery. Many people think of exercise as a way to “stay in shape”, whether that be avoiding weight gain or maintaining muscle gains! However, exercise offers us so much more beyond how it makes us look on the outside. And while I don’t discount anyone’s reasons for or goals of exercising (any excuse to move is fine by me!), it’s the effects on our insides that I’ll be outlining today. Specifically, its effects on our brains.
Exercise & Alzheimer’s Risk Factors
As we learned in Part One of this series, there are many risk factors for Alzheimer’s disease, including vascular risk factors like high cholesterol and high blood pressure, type 2 diabetes and high blood sugar, as well as mood disorders like depression (1). Exercise has been shown to improve each of these risk factors (2, 3, 4). This means that by attenuating Alzheimer’s risk factors, the risk of developing the disease could be reduced. And indeed, in a meta-analysis of 16 studies constituting 160,000 people, they found a 45% reduced risk of Alzheimer’s development in people who regularly engaged in physical activity (5).
Independently of exercise’s effects on Alzheimer’s risk factors, it also directly impacts the brain - and significantly so!
How Exercise Affects Your Brain
Elderly people free of dementia experience hippocampus (a key memory centre of the brain) volume shrinkage at a rate of 1-2% each year (1). However, a 12 month aerobic exercise intervention effectively increased hippocampal volume 2%, offsetting normal age-associated decline. Furthermore, life-long exercises have been found to have larger brain volume and higher-performing executive function than inactive older adults. But why does exercise have this effect? Let’s break it down.
Amyloid Peptide & Tau Protein
You may remember from Part One that the hallmarks of Alzheimer’s are abnormal proteins and peptides (protein fragments) in the brain, like beta-amyloid plaques, tau and neurofibrillary tangles (1). Mice models in which mice are modified to be genetically predisposed to develop Alzheimer’s have shown that exercise decreases these abnormal proteins, and in some studies even shown a clinical improvement in learning and memory (5).
Human studies have found an inverse association between physical activity levels and levels of beta-amyloid plaques in elderly dementia-free subjects. However, a six month aerobic exercise intervention of individuals with mild cognitive impairment (the disease state that occurs before Alzheimer’s that can be reversed through lifestyle change) saw a 24% reduction in a blood biomarker that indicates amyloid plaque levels (5).
Cerebral Blood Flow
Aging is associated with loss of cerebral blood flow, or blood flow to the brain (5). This rate has been measured to be 0.35-0.45% each year in middle-aged and elderly subjects, and leads to accelerated cognitive function decline and increased dementia risk. Compared with healthy people, sufferers of Alzheimer's experience a reduction in cerebral blood flow of up to 40%. A major contributor to this is atherosclerotic (cholesterol plaque build up) changes in Alzheimer’s brains (6). Remember from Part Two, mid-life (people in their forties) cholesterol is associated with Alzheimer’s disease three decades later (7). In fact, those with Alzheimer’s have much more severe atherosclerosis in the circular artery at the base of the brain (the circle of Willis) than healthy age-matched controls (1). A brain healthy diet is a heart healthy diet. Check out my blog on cardiovascular disease here for more information on this!
In older adults, regular exercise improves functioning of the endothelium (lining) of blood vessels throughout the body, which are responsible for producing nitric oxide, and widening blood vessels to enhance blood flow. There is also an improvement of cerebral blood flow to brain areas like the hippocampus. Even healthy middle aged subjects were found to have increased cerebral blood flow at rest to certain areas of the brain including the hippocampus. On the contrary, in healthy individuals, just short periods of inactivity can reduce cerebral blood flow. This is why it is important to avoid sedentary lifestyle patterns - even if you do your exercise for an hour but then sit for the rest of the day, you are still spending 23 hours potentially harming your brain.
Inflammation
“Inflammaging” is a term coined to describe an hypothesis that aging goes hand in hand with low-grade chronic inflammation, and is considered to be a driving factor of Alzheimer’s. Inflammation is a normal immune response in the body. Acute inflammation as occurs when battling an illness or healing from an injury is healthy and normal. However, chronic inflammation, inflammation that does not resolve but continues to perpetuate, is harmful. Specifically in Alzheimer’s, an immune cell called microglia are “activated” when neuro-inflammation occurs (8). What is usually a component of our brain that helps us stay healthy becomes a hostile and aggravating character that initiates and progresses Alzheimer’s.
In animal studies, exercise has been shown to reduce the inflammatory response of microglia, indicating the potential for exercise to modulate inflammatory responses in the brain. In older people, studies have found that exercise reduces inflammatory markers and results in improved cognitive test performance.
Neurotrophic Factors
Neurotrophic factors are chemicals that regulate several aspects of brain health, including growth of nerve components, brain plasticity (adaptation of nerve cells), neurotransmission (communication of nerve cells), and hippocampal neurogenesis (production of new nerve cells) (5). One neurotrophic factor is brain derived neurotrophic factor (BDNF). During prolonged exercise, BDNF synthesis increases by two to three times! Some studies have also correlated higher BDNF with enhanced cognitive performance.
Those suffering Alzheimer’s have been found to have low BDNF levels, suggesting that exercise may help delay the onset of the disease. Additionally, high levels of BDNF are associated with low risk of Alzheimer’s. BDNF levels have been associated with subjects’ physical activity levels.
Cardio & Resistance: Which is Best?
While aerobic exercise has been more vigorously studied, more recent evidence suggests that exercise programs that combine both resistance and aerobic training reap the most benefits (5). While aerobic exercise clearly enhances blood flow to the brain as the heart is needing to pump more quickly, leg strength or power has also been shown to be important. A study sought to determine the relationship between leg power and brain structure and cognition (9). They compared these parameters between identical twins, and the twin with the more powerful legs had the more powerful brain (cognition and size) compared to their genetic counterpart. Supporting (once again) the important of lifestyle over genetics. The reasoning for this is that the legs are a significant “pump” of blood around the body (10). This contributes to the brain’s blood supply.
Training intensity needs to be high enough to achieve a heart rate of 70-80% to optimise blood flow to the brain and yield the other benefits including lowering blood pressure and improving cholesterol levels (both Alzheimer’s risk factors). Sessions should last at least 45 minutes and should occur on as many days of the week as possible.
So get moving and work out not just for your muscles and your heart, but also your brain!
Next up, we’ll be looking at differently stress, and some ways in which we can unwind to help our brains thrive!
By Jessica Zabow
Nutritionist (BHSc)
& Yoga Teacher (RYT500)
References:
Edwards III, G.A., Gamez, N., Escobedo Jr, G., Calderon, O., & Moreno-Gonzalez, I. (2019). Modifiable risk factors for Alzheimer’s disease. Frontiers in Aging Neuroscience, 11(146), 1-18. https://doi.org/10.3389/fnagi.2019.00146
Ghadieh, A.S., & Saab, B. (2015). Evidence for exercise training in the management of hypertension in adults. Canadian Family Physician, 51(3), 233-239. Retrieved from https://www.cfp.ca/content/cfp/61/3/233.full.pdf
Yang, D., Yang, Y., Li, Y., & Han, R. (2019). Physical exercise as therapy for type 2 diabetes mellitus: From mechanism to orientation. Annals of Nutrition and Metabolism, 74(1), 313-321. https://doi.org/10.1159/000500110
Murri, M.B., Ekkekakis, P., Magagnoli, M., Zampogna, D., Cattedra, S., Capobianco, L., Serafini, G., … Amore, M. (2019). Physical exercise in major depression: Reducing the mortality gap while improving clinical outcomes. Frontiers in Psychiatry, 9(762), 1-10. https://doi.org/10.3389/fpsyt.2018.00762
De la Rosa, A., Olaso-Gonzalez, G., Arc-Chagnaud, C., Millan, F., Salvador-Pascual, A., Garcia-Lucerga, C., Blasco-Lafarga, C., ... Gomez-Cabrera, M.C. (2020). Physical exercise in the prevention and treatment of Alzheimer's disease. Journal of Sport and Health Science, 9(5), 394-404. https://doi.org/10.1016/j.jshs.2020.01.004
Govindpani, K., McNamara, L.G., Smith, N.R., Vinnakota, C., Waldvogel, H.J., Faull, R.L.M., & Kwakowsky, A. (2019). Vascular dysfunction in Alzheimer’s disease: A prelude to the pathological process or a consequence of it? Journal of Clinical Medicine, 8(5), 1-57. https://doi.org/10.3390/jcm8050651
Solomon, A., Kivipelto, M., Wolozin, B., Zhou, J., & Whitmer, R.A. (2009). Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later. Dementia and Geriatric Cognitive Disorders, 28(1), 75-80. https://doi.org/10.1159/000231980
Hemonnot, A., Hua, J., & Hirbec, H. (2019). Microglia in Alzheimer’s disease: Well-known targets and new opportunities. Frontiers in Aging Neuroscience, 11(233), 1-20. https://doi.org/10.3389/fnagi.2019.00233
Steves, C.J., Mehta, M.M., Jackson, S.H.D., & Spector, T.D. (2016). Kicking back cognitive ageing: Leg power predicts cognitive ageing after ten years in older female twins. Gerontology, 62(2), 138-149. https://doi.org/10.1159/000441029
Volpe, E.F.T., Resqueti, V.R., da Silva, A.A.M., Gualdi, L.P., & Fregonezi, G.A.F. (2020). Supervised exercise protocol for lower limbs in subjects with chronic venous disease: An evaluator-blinded, randomised clinical trial. Trials, 21(1), 1-9. https://doi.org/10.1186/s13063-020-04314-1