A Tour of Alzheimer’s Disease.
Dr. Trudi Deakin – Chief Executive of X-PERT Health/14 June 2017
Welcome to a tour of Alzheimer’s Disease. Alzheimer’s disease (AD) is a condition whereby the brain cells in the regions of the brain involved in cognition (memory processing and learning) stop functioning properly. This is either because they have become damaged, or starved of energy, or both. The process often begins many years, or even decades, before the symptoms of AD start to appear. This suggests that the brain can compensate and overcome the problem for a considerable amount of time before cognition is affected. This is good news as it provides us with sufficient time to repair any damage and ensure that our brain cells receive adequate nutrition to prevent AD occurring!
What is thought to cause AD?
Failure of parts of the brain to metabolise glucose.
Beta-amyloid (Aβ) plaques in the brain.
High insulin levels and insulin resistance.
Fatty acid and cholesterol imbalance in the brain.
The ApoE4 gene.
Failure of parts of the brain to metabolise glucose
In simple terms “metabolism of glucose” means extracting energy from it. In an adult, the brain represents only 2% of total body weight, but consumes about 20% of the oxygen and glucose used by the body . Glucose, usually supplied from carbohydrates, is often considered to be the brain’s preferred fuel. However, people with AD have been shown to have up to 45 percent reduction in the cerebral metabolic rate of glucose . If the brain is relying on glucose for fuel, anything that disrupts glucose being utilised for energy can starve the brain cells leading to cell damage and death of cells. Ultimately this impairs brain function.
The nerve cells in the brain communicate by sending signals to one another. A bit like sending a text message. The small spaces between the nerve cells are called synapses. In AD, the synapses increase in size due to the nerve cells shrinking when they do not receive sufficient fuel. This affects the signal between nerve cells and communication between the nerve cells break down. Similar to trying to send a text message when the mobile phone network is down!
Beta-amyloid (Aβ) plaques in the brain
These are normal protein fragments that accumulate in the brain. In small doses, the brain has an ability to clear them. However, in people with AD, high insulin levels prevent these protein fragments from being broken down. Thus significantly more are present. These fragments form solid masses that also interfere and even stop communication impulses being passed from one nerve call (neuron) to another.
High insulin levels and insulin resistance
It is increasingly being recognised that AD is associated with the metabolic syndrome. This is a cluster of conditions that are associated with insulin resistance, Type 2 diabetes and cardiovascular disease (see number 2 in the prevention section below). AD is frequently referred to as Type 3 diabetes because there is a link with high insulin levels (hyperinsulinaemia) and insulin resistance. It has been established that high insulin levels cause insulin resistance . But there is individual variation in how this impacts on the functioning of different organs and resulting health conditions . Therefore, not all people with Type 2 diabetes are at risk of AD and not everyone with AD is at risk of Type 2 diabetes.
If the insulin resistance affects the brain, this prevents the Aβ plaques from being broken down resulting in excessive accumulation . One study concluded that people with non-diabetic hyperinsulinaemia had double the risk for developing AD compared to those with normal insulin levels .
Fatty acid and cholesterol imbalance in the brain
Nerve cells (neurons) are like electrical wires that transit impulses around the body, including the brain. Just like electrical wires are insulted, so are neurons. The insulation is called the myelin sheath. One of the main building blocks of the myelin sheath is cholesterol. Twenty-five percent of the cholesterol in the body is required by the brain for optimum brain function. Therefore having insufficient cholesterol in the brain will impair brain function.
Cells are involved in everything that happens inside our body. All cells have internal and external walls, just like houses do. In cells, these are called membranes and they comprise of 40 to 80 percent of the entire cell. Houses have doors that allow people and pets in and out. Cell membrane also govern what is allowed to enter and exit the different cells in the body. If the cell membrane starts to malfunction, good things like nutrients struggle to enter the cell. And bad things such as toxins and waste products, cannot get out. All membranes are made out of fats and cholesterol which means that our bodies are largely made out of fat and cholesterol! There needs to be the right mix of saturated and unsaturated fat in the cell membrane to enable it to work properly.
Dysfunction of the nerve cells
High concentration of omega-6 polyunsaturated fatty acids found in man-made vegetable oils are susceptible to damage when mixed with oxygen. This is called oxidation and it alters the structure and function of cell membranes not just in the brain but throughout the entire body. The membranes can become weak and unstable. An abundance of omega-6 polyunsaturated fat in comparison to omega-3 polyunsaturated, monounsaturated and saturated fat can result in dysfunction of the nerve cells increasing the risk or progression of AD.
The ApoE4 gene
Cholesterol is carried to where it is needed in the body by transporters called LDLs. There are many variations of LDL transporters and genes can stipulate which type we have. If we have the ApoE4 version of LDL, it seems to be damaged more easily. The consequence is that the cholesterol can be deposited in the blood vessels rather than being delivered to where it is an essential component of the cell membrane and myelin sheath in the nerve cells .
It is estimated that 15% of people have the ApoE4 gene and this may increase their risk of developing AD. However, the good news is, the ApoE4 gene does not cause AD. It causes people to be more prone to damage and starvation of the brain cells and therefore even more benefits can be reaped from following the lifestyle recommendations listed below.
Vitamin B12 deficiency
This essential vitamin is required for the myelin sheath (nerve cell insulation) to be maintained and function properly. There are several reasons why someone may be deficient in vitamin B12:
as people age they make less stomach acid and this is required to absorb B12 from foods.
taking antacids lowers the amount of acid in the stomach and thus the ability to absorb B12 from foods.
insufficient consumption of foods rich in B12 such as red meat, offal (especially liver) and shellfish such as oysters, mussels and clams
For optimum brain function, Vitamin B12 deficiency should be prevented and if identified, treated.
How can you prevent, halt or even reverse progression of AD?
AD is thought to be a disease of modern civilisation caused by a diet and lifestyle that do not match our human physiology. In this tour of Alzheimer’s Disease, let’s discuss several steps that can be made including:
1. Reduce insulin levels by adopting a real food Mediterranean, low carb or intermittent dietary approach and participate in regular physical activity:
Reducing refined carbs will not only reduce insulin levels and insulin resistance but it will also prevent our cells, tissues and blood vessels becoming excessively glycated i.e. coated in sticky glucose and ceasing to function properly. For the prevention and management of AD, this will enable nerve cells in the brain to obtain sufficient fuel and communicate between one another effectively.
Omitting processed vegetable oils and replacing with stable fats found in real unprocessed foods such as extra-virgin olive oil, wild-caught oily fish, butter from grass-fed cows, eggs and meat from pasture-raised hens and cattle, whole fat milk and dairy foods, will reduce oxidation and ROS production. This will therefore keep cell membranes functioning properly. Cholesterol-containing foods are also rich in the essential nutrient choline, a brain chemical (neurotransmitter) involved in memory processing and learning.
Ensuring an adequate intake of omega-3 polyunsaturated fats because the brain is made out of them and they have a direct effect on the function of the brain .
The best sources are from foods such as fatty fish (eat the skin and flesh), organ meats and egg yolks (from pastured hens). We can get omega-3 from vegetarian sources such as flaxseeds, chia seeds and walnuts but these have to then be converted in the body to the active components, EPA and DHA, and the conversion rate tends to be poor.
Obtaining vegetables, low-carb fruits and salad ingredients rich in natural antioxidants such as vitamins A, D, E and K1 and K2 that assist in reducing oxidation and thus, damage occurring to cell membranes.
Participating in regular physical activity helps glucose to be taken up by cells and converted into energy thereby reducing hyperinsulinaemia and insulin resistance. Exercise (both aerobic and resistance) also stimulates a special protein called brain-derived neurotrophic factor that has been shown to support memory and learning . Maintaining muscle mass as we age has also been shown to reduce excessive oxidation in the body, which will prevent damage to the crucial nerve cells in the brain .
2. Reduce risk factors for the metabolic syndrome
The metabolic syndrome is related to insulin resistance and is defined as having three or more of the risk factors below. The international cut points  are:
Increased waist size: Greater than 94 cm in Caucasian men and greater than 80 cm in Caucasian women, or greater than 90 cm in South Asian men and greater than 80 cm South Asian women
Raised triglycerides: greater than 1.7 mmol/l (or on medication to reduce triglycerides)
Reduced HDL cholesterol: less than 1.03 mmol/l in men; less than 1.29 mmol/l in women
Raised blood pressure: Systolic greater than 130 mmHg; Diastolic greater than 85 mmHg (or on medication to reduce blood pressure)
Increased fasting glucose: Fasting plasma glucose greater than 5.6 mmol/l
Aim to make lifestyle changes (see above) that will improve these clinical indicators. Note, that total cholesterol or LDL cholesterol is not included in this list as these are outdated and inaccurate markers. This is because cholesterol is essential to life and needed by every cell in the body, especially the brain. Cholesterol only ends up where it shouldn’t be (in the blood vessel wall) when the cholesterol transporters (LDL) become small and dense (from high triglyceride and low HDL levels). Small dense LDL and EpoE4 LDL (see above) are easily oxidised (damaged) and then drop their load .
For optimal brain health, be careful with advice to drive your cholesterol level too low, especially if this involves taking statins. Statins may cause cholesterol deficiency in the brain but also block the production of a compound called coenzyme Q10 that is integral to the body making energy and also a crucial antioxidant (preventing the damaging oxidation) in the brain.
3. Provide the brain cells with fuel they can use – ketones
Consider adopting a diet (very low carb or intermittent fasting) that will allow you to be in nutritional ketosis, meaning that your body has adapted to using fat at its preferred fuel rather than carbohydrate. Although glucose is classed as the brain’s primary fuel, carbohydrate is not an essential nutrient because if we do not eat it, 56 g of glucose can be derived from every 100g of protein consumed and 10g of glucose can be derived from every 100g of fat ingested.
Thus, a combination of protein and fat utilisation is required to supply the small amount of glucose still required by the brain in a person fully adapted a carbohydrate-free diet. Thus “The lower limit of dietary carbohydrate compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed” .
However, glucose isn’t the only fuel that that brain can use. It can adapt to a carbohydrate-free, energy-sufficient diet, by utilising ketones for part of its fuel requirements. As glucose production or availability decreases there is a rise in ketone production in the liver in order to provide the brain with an alternative fuel. The brain is more than happy to run on ketones and they can account for around 80 percent of the brain’s energy requirements reducing glucose requirements from around 130 grams per day to just 22 to 28 grams per day.
Ketone fuel, as opposed to glucose fuel, has been referred to as “super-fuel” as ketones generate more energy and fewer damaging by-products called reactive oxygen species (ROS) . It has been suggested that a high carb diet increases risk of AD because it is keto-deficient  and there is clinical trial evidence that ketones do improve cognition in people with AD [16, 17].
4. Reduce stress and improve sleep
Emotional and psychological stresses are lifestyle factors that increase the stress hormone, cortisol. This hormone should provide us with a quick spurt of energy to deal with a threat, but if the stress sticks around for several days, weeks and even years, then it can cause long-term health problems. Cortisol increases blood glucose, which then increases insulin, which then increases insulin resistance.
It also has the opposite effect to exercise on the functioning of the brain, diminishing brain-derived neurotrophic factor and impairing memory and learning abilities . Sleep is a basic human requirement and can be thought of as fasting for the brain, allowing it to recover and regenerate. Sleep disruption has been associated with other insulin resistant conditions such as Type 2 diabetes and obesity . In particular, chronic sleep deprivation in AD may be associated with accumulation of the amyloid plaques as clearance is as much as two-fold faster when sleeping than during waking hours .
Acknowledgements for this blog on A Tour of Alzheimer’s Disease.
It would not have been possible to write this blog without first of all reading the excellent book “The Alzheimer’s Antidote” written by Amy Berger. I encourage anyone who is interested in the subject for personal or professional reasons to obtain copy and become spellbound like I did!
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