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A 10 minute guide to Alzheimer’s & protecting your brain

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In 1907, German psychiatrist Alois Alzheimer had a 51-year-old patient under his care. He noted her behaviour stating memory loss, inability to read and spell normally, forgetting usage of certain objects and inability to comprehend questions. When her brain was examined upon her death, it contained abnormal blockages. This was the first recorded case of Alzheimer’s disease.

Currently, Alzheimer’s is the most common form of dementia, affecting 1 in 9 older adults [1]. Dementia is the decline in thinking, memory, and mental skills severe enough to impact everyday life. Despite this, some people with Alzheimer’s continue to live an enriching life. Understanding the disease is the first step in improving outcomes. Though Alzheimer’s disease treatment is yet to be established, research has progressed since its first known case 115 years ago and the future looks promising. There is rich evidence on practical interventions like the Mediterranean diet that can reduce the risk and delay the symptoms of Alzheimer’s. The Mediterranean diet is an eating pattern that recommends regular intake of whole grains, legumes, olive oil, fruits, and vegetables. Moderate intake of seafood, chicken and dairy is recommended. Processed meat, unhealthy fats, sweets, and alcohol intake is limited. This diet is rich in foods for dementia prevention.

Vascular dementia is the second most common form of dementia and is a result of constricted blood supply to the brain. Diet is known to have a huge positive impact. Protective compounds called anthocyanins are found in blue/red fruits and vegetables such as berries, grapes, plums and cabbage, and can increase blood flow (vasodilation) to the brain and lower inflammation [44]

What happens to the brain in Alzheimer’s disease

The main characteristics of an Alzheimer’s brain is the presence of plaques, tangles and the loss of brain matter. Two types of protein, which normally benefit the brain, become dysfunctional and contribute to brain damage. Processing of one such protein produces amyloid beta which is cleared out as waste. In Alzheimer’s, it accumulates between cells and forms plaques. The brain also produces a structural protein for the stabilisation of brain cells called tau protein. In Alzheimer’s, a defect causes the protein to lose its structural integrity. It begins to form tangles which leads to the breaking down of the cell. As the disease progresses, there is loss of brain matter and decrease in brain size. It is important to note that cognitive functions can still be preserved through healthy brain habits despite the presence of Alzheimer’s pathologies.

What are the risk factors of Alzheimer’s disease?

The good news is many risk factors can be prevented/managed. In a 2020 report, 28 leading dementia experts have compiled 12 risk factors that should be managed to delay or prevent 40% of dementia cases [2]. Some of these include managing obesity, depression, and diabetes, limiting alcohol intake (<21 units/week), stopping smoking, maintaining a healthy blood pressure, increasing social interaction, and physical activity, and avoiding air pollution.

Is Alzheimer's hereditary?

Genetics play an important role but inheriting Alzheimer’s is rare. Less than 1% of the cases are of Familial Alzheimer’s disease where genetic mutations increase the chance of inheritance from parents by 50% [9].

One gene of concern is APOE and it has three main forms: apoE3, apoE4 and apoE2:

  • apoE3 is found in 65-70% of the population is neutral without connection to Alzheimer’s. 
  • apoE2 is protective against Alzheimer’s and found in 5-10% of the population.
  • apoE4, which is carried by 15-20% of humans, is the main risk factor for Alzheimer’s [2].

There is still hope even if you are carrying apoE4. Alzheimer’s induced brain damage was absent in almost 60% of those with apoE4 gene [3]. Research has found that it is possible to preserve cognitive skills despite the presence of Alzheimer’s brain damage. Sister Mary, from the Nun Study (1986) scored 27/30 (excellent) on cognitive tests at the age of 101 despite the presence of severe Alzheimer’s brain damage (second highest damage among 678 nuns) [5]. Positive lifestyle interventions were associated with her mental agility in the face of the disease. 

What causes Alzheimer’s disease?

There are several mechanisms associated with the cause of Alzheimer’s.

Cholinergic hypothesis: The earliest known theory was proposed in the 1970s in relation to the brain chemical involved in memory, learning and attention, called acetylcholine. A destruction of acetylcholine producing cells is noted in Alzheimer’s. Amyloid beta decreases production of this brain chemical [6]. Current drug therapies are based on preventing breakdown of acetylcholine [12].  A recent animal study suggests that long term choline (precursor of acetylcholine) supplementation may reduce brain inflammation and block production of amyloid beta [11]

Oxidative stress theory: The body normally produces harmful by-products during chemical reactions which are efficiently cleared away. Protective compounds neutralize the harmful by-products. When there is an imbalance between protective compounds and clearance of harmful by-products, oxidative stress takes place in brain cells. One of the first markers of Alzheimer’s disease is oxidative stress induced damage to the energy producing area (mitochondria). Energy production in the brain is affected and oxidative damage can promote accumulation of amyloid beta, and increased tangling of tau [7]. Limited studies using medications along with antioxidant supplementation of Vitamin E, C and B vitamins found beneficial effects like slowing progression of Alzheimer’s [12] Research in this field is emerging with exciting antioxidant studies currently underway. The Mediterranean diet is rich in these protective nutrients and is known to decrease oxidative damage of DNA, decrease inflammation and increase the antioxidant defence of the brain [45].

Amyloid cascade theory: The amyloid beta theory of accumulation of amyloid beta between cells and formation of tau tangles is another hypothesis of Alzheimer’s.

Metal hypothesis: Metals like aluminium, mercury and lead can enter the body from the environment. These can enter the brain and contribute to Alzheimer’s disease by increasing amyloid beta production and accumulation [4]. They also cause damage to tau protein and contribute to its tangling [8]. Metals also contribute to oxidative stress. Medication treatment trials like the PBT2 (the IMAGINE trial), targeting toxic metals are being conducted [13].

Infection hypothesis [46,47]: Infection by herpes virus and some bacteria have been linked to development of Alzheimer’s disease. This can lead to increased production of amyloid beta and tau protein. Infections lead to inflammation which can disrupt clearing up of amyloid beta and promote its accumulation. This can fuel further inflammation, leading to brain cells damage. Antibiotics and anti-viral drugs are being tested in Alzheimer’s to determine a suitable treatment. 

How is Alzheimer’s diagnosed?

Alzheimer’s is diagnosed after running multiple tests including conducting a medical history, brain scans, blood tests, neurological tests, mental cognition tests and physical exams [10].

How to prevent Alzheimer's

The good news is there are practical approaches that have shown to lower the risk of getting Alzheimer’s or delay the damage caused. Broadly speaking, they fall into 3 categories

1. Diet- the link between Mediterranean diet and Alzheimer’s?

Multiple reviews have established a strong positive link between following a Mediterranean diet and decreased risk of Alzheimer’s.

16 thousand people studied for 20 years reported 20% less risk of dementia among those with high adherence to the diet [14].
A 2022 review of 36 studies found that following this diet is associated with improved memory and cognition and lower risk of Alzheimer’s [15].
A 2022 compilation of 6 research reviews concluded up to 40% reduced risk of developing age-related cognition disorders in those following a Mediterranean diet [16].
Higher adherence was shown to provide up to 3.5 years of protection against Alzheimer’s damage and bigger brain size and lower amyloid and tau clogs [17][18]. 

What is in the Mediterranean diet? And, what are the functional nutrients that might be playing a role?

Mediterranean diet component

Nutrients

Impact on Alzheimer’s disease

Fatty fish

DHA (healthy omega 3 fat)

  • DHA is the predominant brain fat, promotes structural integrity, increases brain blood flow, increases production of brain cells, decreases production of amyloid beta [23, 24].
  •  Those over the age of 65 years, who consumed 1 portion fish per week had 60% lesser risk of Alzheimer’s [23]

Fruits: blueberries, pomegranates apples, grapes, and citrus fruits

Polyphenols (antioxidants)

Vitamin C

  • Polyphenols increase blood flow to the brain, reduce oxidative stress, and improve connectivity in some brain areas.
  • Long term fruit intake associated with improved memory and lower risk of Alzheimer’s [21, 22]

Green leafy vegetables

Vitamin K, folate, Beta carotene, Vitamin E

  • Antioxidant effect-protect against oxidative stress, decrease tau dysfunction
  • Cognitive health of those who had 1-2 cups per day was 11 years younger compared to non-diet group[20]

Olive oil 

MUFA, PUFA (healthy fats)

Oleuropein (Antioxidant)

  • Protect against amyloid beta and tau accumulation, increase their clearance [19]
  • Supplementing 26g of extra virgin olive oil in those following Mediterranean diet showed improvement in cognitive scores [25]

Nuts (Walnuts)

PUFA (healthy fats)

Antioxidants

  • Fight oxidative stress, dissolve amyloid beta plaques, decrease inflammation [26] [27]
  • Those following a Mediterranean diet supplemented with 30g nuts (walnuts, hazelnuts and almonds) showed improvement in memory and cognitive skills [26]

The MIND diet [48] was created in 2015 that was based on the Mediterranean diet and the DASH diet (Dietary Approaches to Stop Hypertension). The components chosen from both diets were targeted for brain health. The diet promotes regular intake of whole grains, fruits, vegetables, olive oil and limits intake of saturated and trans fat.

2. Physical activity and Alzheimer’s

Regular physical activity is shown to have a positive impact on brain health in Alzheimer’s disease. Exercise promotes creation of new cells and connections in the brain. It helps shift processing of amyloid precursor protein towards creating a healthy product instead of amyloid beta. It also limits inflammation in the brain and helps increase brain size and volume [28]. A 2022 review found that doing aerobic exercises like walking, cycling, swimming for 20-90 minutes two to three times a week improved cognition skills [29]. A 40 mins session of treadmill and stair climbing for 12 weeks was related to increase in blood flow to the brain and building new brain connections [30]. A review of 13 studies concluded that recommended 30 mins of exercise, 3 times a week for brain benefits in those with Alzheimer’s [31].


Type of physical activity 

Duration

Impact on Alzheimer’s disease

Brisk walking

At least 2.5 hrs per week

Reduced risk of Alzheimer’s by 33% [32]

Dancing 

30-60 mins per session, 1-2 times a week 

Increased blood flow to the brain, improved memory when learning dance sequence, improved coordination [33]

Strength training

30 mins per session, 3 times a week

Improvement in memory and cognition skills, increase in reaction time, attention and hand-eye coordination [34]

Yoga

30-60 mins, 1-3 times/ week

Improvement in attention, processing speed and memory [35]

Golf

100mins per session, 1/week

Improvement in memory [36]

Water based exercise (Aquatic therapy)

40-45 mins per session, 2 times a week

Improved flexibility, balance and posture, social interaction and sleep [37] [38]


The NHS recommends the following for those over 65 years of age [39]:

  • Be physically active daily, includes daily chores and light walking
  • For at least 2 days/week, do strength training and flexibility activities like yoga, Pilates, weightlifting, heavy gardening
  • Every week, do 150 minutes of moderate intensity activity (water aerobics, bike riding, hiking) or 75 mins of vigorous intensity (running, swimming, football, martial arts)
  • Reduce sedentary behaviour
3. Sleep and Alzheimer’s

Adequate high-quality sleep is essential for optimum brain functioning. Those who slept too little (<4 hours/24 hrs) or too much (>12.5 hrs/24 hours) had a higher risk of Alzheimer’s [40]. Sleep performs housekeeping functions. During sleep, the fluid in the brain circulates to clean up waste materials, including amyloid beta, thus decreasing its accumulation.  Even in those with apoE4 gene, better sleep quality was related to lower beta amyloid plaques [41]. Those who slept 6-8 hours a night had a lesser risk of dementia [42]. The Alzheimer’s association recommends the following to improve sleep quality [43]:

  • Maintaining regular sleep times 
  • Avoiding stimulants like alcohol, caffeine and nicotine and tv screens
  • Promoting sleep inducing environment like comfortable bedding, room temperature 
  • Being active during the day

 

References

  1. Alzheimer's Association (2021). Facts and Figures. [online] Alzheimer’s Disease and Dementia. 
  2. Livingston, G. et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), pp.413–446.
  3. Liu, C.-C. et al. (2013). Apolipoprotein E and Alzheimer disease: risk, Mechanisms and Therapy. Nature Reviews Neurology, 9(2), pp.106–118.
  4. Wang, L. et al. (2020). Current understanding of metal ions in the pathogenesis of Alzheimer’s disease. Translational Neurodegeneration.
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  8. Bakulski, K.M. et al. (2020). Heavy Metals Exposure and Alzheimer’s Disease and Related Dementias. Journal of Alzheimer’s disease : JAD, [online] 76(4), pp.1215–1242. 
  9. Rare Dementia Support. (n.d.). Understanding FAD. [online] 
  10. Alzheimer’s Association. (2020). How is Alzheimer's Disease Diagnosed? [online] 
  11. Velazquez, R. et al. (2019). Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, 18(6).
  12. Collins, A.E. et al. (2022). Naturally Occurring Antioxidant Therapy in Alzheimer’s Disease. Antioxidants, 11(2), p.213.
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  14. Andreu-Reinón, M.E. et al. (2021). Mediterranean Diet and Risk of Dementia and Alzheimer’s Disease in the EPIC-Spain Dementia Cohort Study. Nutrients, 13(2), p.700. 
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  18. Ballarini, T. et al. (2021). Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age. Neurology. [online] 
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  21. Dal-Pan, A. et al. (2017). Cognitive-Enhancing Effects of a Polyphenols-Rich Extract from Fruits without Changes in Neuropathology in an Animal Model of Alzheimer’s Disease. Journal of Alzheimer’s disease: JAD, [online] 55(1), pp.115–135.
  22. Yang, W. et al. (2021). Effect of Polyphenols on Cognitive Function: Evidence from Population-based Studies and Clinical Trials. The journal of nutrition, health & aging, 25(10), pp.1190–1204. 
  23. Morris, M.C. et al. (2003). Consumption of Fish and n-3 Fatty Acids and Risk of Incident Alzheimer Disease. Archives of Neurology, [online] 60(7), p.940. 
  24. Lee, B. et al. (2018). Effect of Varying Concentrations of Docosahexaenoic Acid on Amyloid Beta (1–42) Aggregation: An Atomic Force Microscopy Study. Molecules, 23(12), p.3089.
  25. Mazza, E. et al. (2018). Effect of the replacement of dietary vegetable oils with a low dose of extravirgin olive oil in the Mediterranean Diet on cognitive functions in the elderly. Journal of Translational Medicine, 16(1).
  26. Chauhan, A. et al. (2020). Beneficial Effects of Walnuts on Cognition and Brain Health. Nutrients, 12(2), p.550.
  27. Theodore, L.E. et al. (2020). Nut Consumption for Cognitive Performance: A Systematic Review. Advances in Nutrition, 12(3), pp.777–792.
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  32. American Academy of Neurology (2022.). Physical Fitness Linked to Lower Risk of Alzheimer’s Disease. [online] 
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