Alzheimer’s & Nutrition

Nutrition has the ability to either promote or undermine our health. The brain is the most vascular organ, and while it only accounts for two percent of our body weight, it can use up to fifty percent of our energy (1). This means that it is highly vulnerable to oxidative stress, and is very much reliant on a healthy cardiovascular system. You can find more information on cardiovascular health here. Additionally, the brain is composed of omega 3 fats, which are highly sensitive to “lipid peroxidation”, a process where oxidative stress damages fats, ultimately contributing to Alzheimer’s (2).

The drivers of Alzheimer’s disease we learned about in Part One (glucose and lipid dysregulation, oxidative stress and inflammation) can all be impacted either positively or negatively by our diet (3). This means that our food choices can influence whether or not we protect or harm our brain. This blog will look at a key diet studied for its impact on brain health, Alzheimer’s as “Type 3 Diabetes”, the nuance of dietary fats, and some key brain foods.

The MIND Diet

Two diets have been studied in the investigation of cardiovascular risk: the Mediterranean diet and the DASH diet (dietary approach to stop hypertension). While both diets were found to be effective in reducing cardiovascular disease and high blood pressure, it was also noted that those who adhered to the diets experienced less incidence of cognitive decline (4). Both the Mediterranean and DASH diets were low in saturated (primarily animal fats), refined carbohydrates (sugar, processed foods, refined grains) and high in fibre (fruits, vegetables, whole grains and legumes) and unsaturated fats (plant fats like olive oil, and nuts and seeds, and fish).

The MIND diet (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) adapted these diets to also include foods known to benefit brain health like green leafy vegetables and berries. The MIND diet created lists of brain healthy foods and brain harming foods, and formulated a scoring system to determine adherence.

The MIND diet emphasises “… natural plant-based foods and limits intake of animal and high saturated fat foods”. What did they find in their studies?

Within the Manhattan Aging Project of 1306 people, the MIND diet score was positively and significantly associated with slower rate of cognitive decline. Between the lowest and highest score tertiles (highest and lowest third of compliance level), there was a 7.5 year equivalent difference in cognitive age between subjects (4).

In terms of Alzheimer’s risk found after a 4.5 year follow-up, there was a 53% reduced risk between the highest and lowest tertiles, and a 35% reduced risk between the middle and lowest tertiles (5).

This highlights that even modest adherence showed substantial prevention of Alzheimer’s.

Statistical adjustment accounted for any potential confounders (other factors that may have actually accounted for the results rather than diet) including age, sex, education, energy intake, the main Alzheimer’s gene APOE4, smoking, physical activity and participation in cognitive activities.

That is the power of diet!

Type 3 Diabetes

Those suffering diabetes have more than twice the risk of developing Alzheimer’s (6). Insulin resistance in the brain has such a strong link with the development of Alzheimer’s disease that some people are using the term “Type 3 Diabetes” to refer to Alzheimer’s. Check out my blogs on insulin resistance to learn my about it here. Insulin is very protective in the brain, and glucose is the brain’s preferred fuel. When insulin cannot communicate with brain cells to exert its benefits, and when insulin is unable to allow glucose into cells, the brain cannot function well (7). Additionally, high glucose in the blood leads to inflammation, oxidative stress, and the production of damaging compounds called advanced glycation end products. Ultimately, insulin resistance in the brain compromises clearance of amyloid plaques while also promoting its production, thereby driving Alzheimer’s.

Refined carbohydrates and foods high in saturated fat and trans fat contribute to insulin resistance - the same foods independently found to contribute to Alzheimer’s (8). The best diet to reduce and even reverse insulin resistance is a diet that is low in saturated fat and high in dietary fibre. A diet that focuses on unrefined plant foods and is low in animal and processed foods. Let’s take a deeper look into dietary fat quality.

Dietary Fats: Not Created Equal

There are several types of fat in our diet, and they have very different effects in our bodies.

Saturated Fats

Saturated fats have been shown to contribute to many different disease states as well as all-cause mortality (9). Why this fat is so harmful is because it distorts many of our bodies’ functions on a cellular level, including impacting receptor function and not allowing cells to communicate with each other properly. Communication in the body is paramount to it being healthy. Saturated fat impairs insulin receptors leading to insulin resistance, it impairs cholesterol receptors leading to excess LDL “bad” cholesterol, it disturbs the gut microbiome (check out my blog here for a deep dive on this fascinating topic!), and it increases the production of amyloid plaques while also disturbing the blood brain barrier - the first line of defence of the brain - leading to toxicity, inflammation and oxidative stress (8, 10, 11, & 2).

We want to keep our saturated fat low, but the Western diet is inundated with saturated fat. Also, there is a school of nutritional thinking that saturated fat actually isn’t bad for us. This is the equivalent of climate denialism. The scientific consensus clearly demonstrates that saturated fat is harmful. However, people like to hear good news about their bad habits and this creates a window of opportunity to cash in on book sales and speaking gigs. The result: public confusion about what’s healthy and apathy about food choices because apparently “no one really knows what’s healthy anyway!”. This is not true. The science is clear. And saturated fat is bad news.

Astonishingly, one study found a 60-70% higher risk of dementia between highest and lowest saturated fat intake based on cognitive test scores (12). It is important to understand that it is our mid-life health which determines our risk of developing Alzheimer’s disease. The disease process begins decades before the first symptoms arise. In fact, one study found that high mid-life (people in their 40s) cholesterol increased Alzheimer’s disease risk three decades later (13). Saturated fat has the largest impact on cholesterol levels, as well as trans fat, refined carbohydrates, and dietary cholesterol.

Polyunsaturated Fats

Polyunsaturated fats (PUFAs) come in two main forms: omega 3 and omega 6. Omega 3 fats are anti-inflammatory and omega 6 fats are more pro-inflammatory. The “short chain” forms of these fats are essential - meaning we must obtain them from our diet as our body cannot make them (14).

A diet higher in polyunsaturated and lower in saturated fats are associated with better health - including brain health. A “long chain” PUFA called DHA is very important for the brain. Our body can convert “short chain” omega 3 into “long chain” omega 3 like DHA, however it cannot do this very effectively. Furthermore, if omega 6 fats are high, omega 3 conversion is even more inhibited. This is why omega 6 fats should be kept low, and omega 3 fats increased.

Foods high in omega 3 are fish (more on this later), and omega 3 rich seeds flax/linseeds, chia seeds, and hemp seeds. Walnuts have the highest omega 3 of the nuts, but are lacking compared to the omega 3 rich seeds. Foods high in omega 6 are vegetable oils like safflower, soybean and corn oils. This is why fried foods should be avoided.

Monounsaturated Fat

These fats are likely either beneficial or benign when it comes to brain health, and are high in olive oil and avocados.

Trans Fat

This fat is found naturally in animal products, however it is the man-made form that is of concern (15). They are also known as hydrogenated fats or oils: where unsaturated fats are transformed to act like saturated fats - they go from liquid to solid. Trans fat is high in margarine and is used in processed goods like cakes and cookies. Trans fats drive Alzheimer’s, diabetes, and vascular illness - which (as I’m sure you have gathered by now!) are all very much interconnected.

Cholesterol

This fatty substance is made by your brain. Often people will say that a high cholesterol diet is important for the brain. However, quite ironically, cholesterol cannot pass through a healthy blood brain barrier (16). While saturated fat increase blood cholesterol more than dietary cholesterol, dietary cholesterol still contributes to serum cholesterol. Cholesterol is high in eggs, seafood, meat and dairy.

Meet you Modern Meat

The meat we eat today is very different from wild meat, the meat our ancestors ate. Modern meat is much higher in fat, and has three to four times more saturated fat and three to four times less polyunsaturated fat than wild meat like antelope our ancestors would have eaten (17).

The following diagram illustrates the proportions of SFA, PUFA and MFA in different foods.

Figure One: Fatty acid distribution in various foods.

Here you can see that land animal foods and coconut oil are high in SFA, and salmon and flaxseed are high in omega 3 and low in saturated fat. Some of you might be thinking “but the MIND diet included poultry“, but chicken is clearly also high in saturated fat. Poultry was included in the MIND diet not because it is brain-healthy, but because it is less unhealthy compared to red meat. It was included not for its health benefits, but rather to aid compliance by providing an alternative to red meat.

Refined Carbohydrates

The Western diet is high in saturated fats AND refined carbohydrates such as processed grains, sugar, and fruit juice (18). Refined carbohydrates are low in fibre, high in calories, and low in micronutrients. This is why they are often referred to as “empty calories”. They are easy to over eat and lead to weight gain and fat formation, they also overwhelm the body’s ability to process glucose - its preferred fuel.

You might be surprised that fruit juice is on this list. But think for a moment of sitting down to eating a plate of four whole apples. Just the idea might seem daunting! This would take a long time, and you probably wouldn’t have the appetite to get through them all in one go! Now think about sitting down to a glass of apple juice. This you might find easy to do alongside a whole plate of food! Well there is just as much “sugar” in the four apples as there is in the glass of juice. However, the whole apples are bound to fibre, which slows down the absorption of the fruit sugar into the blood. It also takes A LOT LONGER to eat four apples than it does to drink them, which further slows down the absorption of sugar into the blood. This is why it is so important to talk about food as it exists in its “complex”, because even the same food processed differently can have a VERY different impact.

Refined carbohydrates contribute to type 2 diabetes, which we know predisposes us to Alzheimer’s disease (19). Sweetened beverages and fruit juice have been found to reduce total brain volume as well as the size of the hippocampus which is an important structure in memory and which decays by 80% in Alzheimer’s patients (20). Additionally, these beverages were associated with poorer memory scores with an equivalent difference in cognitive age between 3.5 and 13 years for memory.

Something Fishy

The MIND diet includes fish in its brain healthy food group. However, only one serving per week is recommended. This is because studies have found that there is no further cognitive benefit to fish consumption over one serve per week (4). But why would this be? It has been shown that contaminants in fish like persistent organic pollutants, heavy metals and microplastics undermine the antioxidant and anti-inflammatory benefits of fish (21, 22). This is why it is suggested to consume smaller fish lower on the food chain, where bioaccumulation of toxins is lower.

While fatty fish like salmon are a good source of “long chain” omega 3 fats (as shown in Figure One above), fish do not make these fats. In fact, microalgae, a sea plant, make these fats. What happens then is bioaccumulation: fish eat algae, then fish eat algae-eating fish , and UP the food chain we go until people eat fish who have eaten fish who have eaten fish who have eaten algae. Ultimately, the diet of fish determines how much omega 3 they have. For example, farmed fish fed vegetable oils and soybeans have MUCH lower omega 3 and MUCH higher omega 6 levels (23). Turns out “you are what you eat” applies to fish too! In fact, farmed fish are beginning to be fed microalgae oils high in omega 3 to help shift the balance back to their wild cousins’ profiles. You can cut out the middle fish however and access these oils directly.

Berries & Greens: Your Brain’s Favourite Fruit & Veg

Berries and green leafy vegetables were key foods added to the MIND diet due to their known cognitive benefits.

Berries are high in antioxidants like anthocyanins, which give them their red, blue and black colours. These antioxidants are important for the brain as it does not have the ability to manage its oxidative stress well. Remember, the brain uses up to 50% of our energy and is primarily composed of fats which are oxidised easily. This is what makes berries so important for the brain.

These “polyphenol” antioxidant compounds found in berries cross the blood brain barrier and scavenge the damaging reactive oxygen species that cause oxidative stress, as well as activating antioxidant enzyme activity. Even a small amount of blueberries (150 g) have been shown to improve mild cognitive impairment, the condition that precedes Alzheimer’s (24). Making it an easy and delicious dietary change to help your brain! Berries have also been shown to exert anti-glycaemic effects - reducing simple sugar absorption and high insulin release with refined carbohydrates - as well as improving cardiovascular health (25). It is therefore possible that berries exert brain-healthy benefits through various mechanisms!

Green leafies including spinach, kale, collards and lettuce have been found to be linearly associated with slower cognitive decline - the more you eat, the healthier your brain. One study found an 11 year equivalent difference in cognitive age between those that who ate 1-2 serves per day and those who rarely or never ate leafy greens (26). Leafy greens contain folate, vitamin K and a carotenoid called lutein (as well as many other wonderful nutrients!) and it is thought that these work synergistically to exert their benefits. Consumption of leafies were found have a laundry list of benefits: including reduced brain loss, peroxidation (lipid damage), oxidative stress, mitochondrial dysfunction and neuro-inflammation. Amazingly, they have also shown to attenuate Alzheimer’s gene activity, thereby reducing plaques via EPIGENETICS.

The Gut Link

The gut microbiota determines our bodies’ functions - including metabolism and cognition. If you’re not familiar with this amazing ecosystem, check out my blog here. Good gut bacteria produce short chain fatty acids (SCFAs) after you eat fibre (27). These SCFA support the integrity of the gut lining, but also the blood brain barrier (28). Remember, this lining is your brain’s first line of defence. When it is dysfunctional, your brain is in trouble. Recently, it has been discovered that SCFAs can cross the blood brain barrier and enter the brain, potentially reducing oxidative stress and assisting with Alzheimer’s prevention. The gut is the greatest source of inflammation in the body - and the amount that is produced is determined by what we eat (29). The MIND diet is an anti-inflammatory diet.

Alzheimer’s patients have been shown to have a different microbiota compared to healthy subjects. What’s amazing is that when a stool sample from a patient with Alzheimer’s disease is transferred faecally into a “germ free” mouse (a mouse with a sterile colon), that mouse develops Alzheimer’s disease. A healthy gut creates a healthy brain, and dietary fibre and plant diversity create a healthy gut (30). See here for more information on this fascinating topic.

Clearly Alzheimer’s is a complicated disease that has multiple drivers including metabolic and cardiovascular risk factors. However, I hope that you can see how a dietary pattern low in saturated fat, high in healthy polyunsaturated fat, and low in refined carbohydrates and abundant in fruits, vegetables, whole grains, legumes, while showcasing leafy greens and berries can address risk factors of Alzheimer’s on various levels, while also being able to potentially attenuate existing mild cognitive impairment.

Remember what the MIND diet study found: even moderate changes make a difference. So start small, slowly adapt, and form sustainable new healthy habits that will support the longevity and resilience of your brain!

Coming up, we’ll look at the science of exercise and Alzheimer’s!

Written by Jessica Zabow
Nutritionist (BHSc)
& Yoga Teacher (RYT500)

---

References

1. Chandra, A., Li, W.A., Stone, C.R., Geng, X., & Ding, Y. (2012). The cerebral circulation and cerebrovascular disease I: Anatomy. Brain Circulation, 3(2), 45-56. https://doi.org/10.4103/bc.bc_10_17

2. Chew, H., Solomon, V.A., & Fonteh, A.N. (2020). Involvement of lipids in Alzheimer's disease pathology and potential therapies. Frontiers in Physiology, 11(598), 1-28. https://doi.org/10.3389/fphys.2020.00598

3. Sherzai, D., & Sherzai, A. (2019). Preventing Alzheimer’s: Our most urgent health care priority. American Journal of Lifestyle Medicine, 13(5), 451-461. https://doi.org/10.1177/1559827619843465

4. Morris, M.C., Tangney, C.C., Wang, Y., Sacks, F.M., Barnes, L.L., Bennett, D.A., & Aggarwal, N.T. (2015). MIND diet slows cognitive decline with aging. Alzheimer's Dementia, 11(9), 1015-1022. https://doi.org/10.1016/j.jalz.2015.04.011

5. Morris, M.C., Tangney, C.C., Wang, Y., Sacks, F.M., Bennett, D.A., & Aggarwal, N.T. (2015). MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer's Dementia, 11(9), 1007-1014. https://doi.org/10.1016/j.jalz.2014.11.009

6. 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

7. Ferreira, L.S.S., Fernandes, C.S., Vieira, M.N.N., & De Felice, F.G. (2018). Insulin resistance in Alzheimer’s Disease. Frontiers in Neuroscience, 12(830), 1-11. https://doi.org/10.3389/fnins.2018.00830

8. Luukonen, P.K., Sadevirta, S., Zhou, Y., Kayser, B., Ali, A., Ahonen, L., Lallukka, S., … Yki-Jarvinen. (2018). Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars. Diabetes Care, 41(8), 1732-1739. https://doi.org/10.2337/dc18-0071

9. Yao, X., Xu, X., Wang, S., & Xia, D. (2021). Associations of dietary fat intake with mortality from all causes, cardiovascular disease, and cancer: A prospective study. Frontiers in Nutrition, 40(3), 1060-1070. https://doi.org/10.1016/j.clnu.2020.07.007

10. Chiu, S., Williams, P.T., & Krauss, R.M. (2017). Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidaemia: A randomised controlled trial. PLoS One, 12(2), 1-14. https://doi.org/10.1371/journal.pone.0170664

11. Lobionda, S., Sittipo, P., Kwon, H,Y., & Lee, Y.K. (2019). The role of gut microbiota in intestinal inflammation with respect to diet and extrinsic stressors. Microorganisms, 7(8), 1-17. https://doi.org/10.3390/microorganisms7080271

12. Okereke, O.I., Rosner, B.A., Kim, D.H., Kang, J.H., Cook, N.R., Manson, J.E., Buring, J.E., ... Grodstein, F. (2012). Dietary fat types and 4-year cognitive change in community dwelling older women. Annals of Neurology, 72(1), 124-134. https://doi.org/10.1002/ana.23593

13. 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(), 75-80. https://doi.org/10.1159/000231980

14. Santos, H.O., Price, J.C., & Bueno, A.A. (2020). Beyond fish oil supplements: The effects of alternative plant sources of omega-3 polyunsaturated fatty acids upon lipid indexes and cardiometabolic biomarkers. Nutrients, 12(10), 1-19. https://doi.org/10.3390/nu12103159

15. Morris, M.C., & Tangney, C.C. (2014). Dietary fat composition and dementia risk. Neurobiology of Aging, 35(2), S59-S64. https://doi.org/10.1016/j.neurobiolaging.2014.03.038

16. Saeed, A.A., Genove, G., Li, T., Lutjohann, D., Olin, M., Mast, N., Pikuleva, I.A. … Bjorkhem, I. (2014). Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain. Journal of Biological Chemistry, 289(34), 23712-23722. https://doi.org/10.1074/jbc.M114.556159

17. Cordain, L., Watkins, B.A., Florant, G.L., Keller, M., Rogers, L., & Li, Y. (2002). Fatty acid analysis of wild ruminant tissues: Evolutionary implications for reducing diet-related chronic disease. European Journal of Clinical Nutrition, 56(3), 181-191. https://doi.org/10.1038/sj.ejcn.1601307

18. Francis, H.M., & Stevenson, R.J. (2011). Higher reported saturated fat and refined sugar intake is associated with reduced hippocampal-dependent memory and sensitivity to interoceptive signals. Behavioural Neuroscience, 125(6), 943-955. https://doi.org/10.1037/a0025998

19. Moreira, P.I. (2013). High-sugar diets, type 2 diabetes and Alzheimer's disease. Clinical Nutrition, 16(4), 440-445. https://doi.org/10.1097/MCO.0b013e328361c7d1

20. Pase, M.P., Himali, J.J., Jacques, P.F., DeCarli, C., Satizabal, C.L., Aparicio, H., Vasan, R.S., ... Seshadri, S. (2017). Sugary beverage intake and preclinical Alzheimer's disease in the community. Alzheimer's Dementia, 13(9), 955-964. https://doi.org/10.1016/j.jalz.2017.01.024

21. Hong, M.Y., Lumibao, J., Mistry, P., Saleh, R., & Hoh, E. (2015). Fish oil contamined with persistent organic pollutants reduces antioxidant capacity and induces oxidative stress without affecting its capacity to lower lipid concentrations and systemic inflammation in rats. The Journal of Nutrition, 145(5), 939-944. https://doi.org/10.3945/jn.114.206607

22. Prust, M., Meijer, J., Westerink, R.H.S. (2020). The plastic brain: Neurotoxicity of micro- and nanoplastics. Particle and Fibre Technology, 17(1), 1-16. https://doi.org/10.1186/s12989-020-00358-y

23. Santigosa, E., Brambilla, F., & Milanese, L. (2021). Microalgae oil as an effective alternative source of EPA and DHA for gilthead sea bream (Sparus aureate) aquaculture. Animals, 11(4), 1-17. https://doi.org/10.3390/ani11040971

24. Subash. S., Essa, M.M., Al-Adawi, S., Memon, M.A., Manivasagam, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557-1566. https://doi.org/10.4103/1673-5374.139483

25. Calvano, A., Izuora, K., Oh, E.C., Ebersole, J.L., Lyons, T.J., & Basu, A. (2019). Dietary berries, insulin resistance and type 2 diabetes: An overview of human feeding trials. Food Function, 10(10), 6227-6243. https://doi.org/10.1039/c9fo01426h

26. Morris, M.C., Wang, Y., Barnes, L.L., Bennett, D.A., Dawson-Hughes, B., & Booth, S.L. (2018). Nutrients and bioactives in green leafy vegetables and cognitive decline. American Academy of Neurology, 90(3), e1-e9. https://doi.org/10.1212/WNL.0000000000004815

27. Silva, Y.P., Bernardi, A., & Frozza, R.L. (2020). The role of short-chain fatty acids from gut microbiota in the gut-brain communication. Frontiers in Endoocrinology, 11(25), 1-14. https://doi.org/10.3389/fendo.2020.00025

28. Rutsch, A., Kantsjo, J.B., & Ronchi, F. (2020). The gut-brain axis: How much microbiota and host inflammasome influence brain physiology and pathology. Frontiers in Immunology, 11(604179), 1-24. https://doi.org/10.3389/fimmu.2020.604179

29. Hakansson, A., & Molin, G. (2011). Gut microbiota and inflammation. Nutrients, 3(6), 637-682. https://doi.org/10.3390/nu3060637

30. McDonald, D., Hyde, E., Debelius, J.W., … Knight, R. (2018). American gut: An open platform for citizen science microbiome research. mSystems, 3(3), 1-28. https://doi.org/10.1128/mSystems .00031-18