Alzheimer’s disease is a severe cognitive health disorder that affects approximately 50 million people around the world. It is associated with a high mortality rate and is a massive financial burden on healthcare provision in the Western World, but it is possible that this does not have to be the case.
Alzheimer’s disease is considered to be among the ‘diseases of civilization’, suggesting that it is mainly caused by poor lifestyle choices and unhealthy, contemporary Western diets – both contributory factors that are linked to the onset of many modern chronic diseases including diabetes.
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This article explores the suggestion that Alzheimer’s disease is a form of diabetes known as ‘Type 3’ – a suggestion based on the role that both insulin resistance and glucose metabolism play in the three central pathological features of Alzheimer’s.
What is Alzheimer’s Disease?
The most common form of dementia, Alzheimer’s disease specifically affects the areas of the brain controlling language, thought and memory. It is characterized by the pathology of a build-up of oligomerized β-amyloid plaques in between the nerve cells, tau tangles that build-up inside of cells and brain tissue atrophy of the hippocampus initially followed by other areas.
Alzheimer’s disease generally worsens over time, though the symptoms can vary immensely. The first clear sign of Alzheimer’s disease is forgetfulness to the point where it is affecting normal day functioning at either home or work. This is often first noticed by a friend or family member, and the disease can cause the sufferer to become confused, misplace things, struggle with language or become lost in normally familiar places.
Initial changes begin at the microscopic level before any noticeable symptoms appear. The brain is comprised of 100 billion neurons (nerve cells) with each one connected to many others via synapses to form complex communication networks. As well as these nerve cells, the brain also includes cells that are specialized to support and nourish the nerve cells.
Each group of nerve cells is designed to undertake a specialized task – some nerve cells are involved in learning, thinking and memory whereas others help control sight, hearing, smell or movement. Each brain cell operates like a minute factory, receiving supplies of nourishment, generating energy, creating new cells and disposing of waste.
Cells are also able to process and store information, as well being able to communicate with other cells. In order to function properly, these cells require large amounts of fuel (glucose) and oxygen.
As the co-ordination of this dynamic process breaks down, Alzheimer’s disease begins to take hold. Problems in one area then spread into other areas and crucial cells start to lose their ability to function correctly and begin to die off. Eventually, the whole network starts to break down.
The Link Between Diabetes and Alzheimer’s Disease
Having type 2 diabetes could potentially increase the risk of Alzheimer’s disease. While this is a shocking assertion, it is one that is quickly gathering supporting research and evidence to suggest this may be the case.
The Diabetes Association website states that: “People that have insulin resistance, in particular those with type 2 diabetes, have an increased risk of suffering from Alzheimer’s disease estimated to be between 50 % and 65 % higher”.
Type 2 diabetes interferes with the cells’ ability to retrieve glucose from the blood. This can be due to two reasons – the cells are not responding to insulin and using it efficiently (known as insulin resistance) or the pancreas is not producing enough insulin.
With Alzheimer’s disease it seems that, in some individuals, a very similar thing is happening, specifically in the brain. Insulin helps the neurons in the brain to absorb glucose for healthy and efficient functioning, but if the cells in the brain become resistant to insulin this can lead to persistently high blood sugar levels causing damage to neurons. At the same time the cells are effectively starved of fuel. Both these factors can contribute to the pathology that eventually leads to Alzheimer’s disease.
The link between these two conditions is so prominent that Alzheimer’s disease is now often referred to as ‘Type 3 diabetes’.
The Role of Insulin in the Body
Insulin is produced in response to eating food and helps glucose (i.e. fuel) enter cells in the body where it is needed for energy. Insulin also stimulates protein synthesis and if levels are low, or cells become insulin resistant, then muscle wastage may occur. It is also a trophic factor (i.e. growth factor) for brain cells – supporting the maintenance of neurons. Both high and low levels of insulin can have negative effects on the brain.
Insulin Resistance and Alzheimer’s Disease
Insulin resistance occurs as the result of a diet which is too high in sugary and carbohydrate-rich foods over a long period of time, for example biscuits, cakes, sweet snacks and sugary drinks. These foods result in high levels of insulin being released by the pancreas and when insulin receptors (on cells) are constantly exposed to high levels of insulin they down regulate and become resistant to insulin – in other words they ignore insulin.
This leads to a vicious cycle as blood glucose rises and then insulin levels rise further leading to more stimulation of receptors and then more resistance. This has a number of negative consequences.
Thus, insulin resistance is a condition where the body can produce insulin but does not make effective use of it. When this happens, glucose accumulates in the blood instead of being absorbed into cells and used for energy – this may eventually lead to type 2 diabetes.
The Role of Insulin in the Brain
Insulin stimulates brain cells to take up glucose where it is used for energy production; crucial in the synthesis of important brain chemicals known as neurotransmitters which are needed for efficient communication within the brain. Insulin in the brain also has neurotrophic effects (i.e. it supports growth).
It has long been known that Alzheimer’s disease is linked to plaques and tangles in the brain, though it has been unclear how these abnormalities occur. It is now known however, that insulin does play a key part in the cause of the three central pathological features of Alzheimer’s disease, those being brain atrophy of the hippocampus, beta-amyloid plaques and tau tangles.
Beta-amyloid plaques are deposits of protein which can accumulate within the spaces between nerve cells. β-amyloid is made from ‘amyloid precursor protein’ (APP), which can have either a valuable or neurotoxic outcome.
In a healthy brain, APP will be processed to form a number of peptides which support the maintenance of neurons and synapses. On the other hand, factors such as inflammation, toxicity or lack of key nutrients can drive APP to be processed via another pathway which results in the production of β-amyloid.
The formation of insoluble aggregations of β-amyloid blocks cell to cell communication. Some therapies focus on stopping β-amyloid from forming or breaking it down. However, these are not addressing the underlying problems that are driving the pathology – namely inflammation, toxicity or lack of key nutrients.
Smaller volumes of β-amyloid will generally remain soluble, though larger levels can form plaques within the brain. Insulin is important in this case because the same enzyme will degrade both insulin and β-amyloid, meaning that they will be in competition with one another. Because of this, too much insulin within the brain can reduce β-amyloid clearance and cause it to build up.
Dr Craft asked one group of research volunteers to follow the high-fat/high-sugar diet for four weeks, and another group to follow a low-fat/low-sugar diet. The preliminary results show that, in just a month, the participants on the high-fat/high-sugar diet had changes in beta-amyloid in the spinal fluid that may adversely impact its clearance from the brain and significant increases in LDL cholesterol.
Those on the low-fat/low-sugar diet had improved beta-amyloid, insulin, and cholesterol profiles. Dr. Craft speculated that the temporary insulin resistance induced by the high-fat/high-sugar diet interfered with the clearance of beta-amyloid, perhaps by affecting the enzyme in the liver that normally clears beta-amyloid from the bloodstream.”
Tau tangles are twisted fibers of tau proteins. Normally, tau proteins have a role in promoting a stable internal structure within the cell, but when these tau tangles become hyperphosphorylated they form insoluble tangles inside the cell which can interfere with intracellular transport.. Generally, most people will develop some tangles as they age but those suffering from Alzheimer’s disease will develop many more.
These plaques and tangles can block communication within cells, disrupting the processes required for the cells to survive. As nerve cells are destroyed and killed, this causes personality changes and memory failures, as well as problems with undertaking regular, everyday activities.
Research increasingly proposes that insulin resistance or dysfunction is linked to the overproduction of tau tangles. The phosphorylation of tau is regulated by the enzyme glycogen synthase kinase, and insulin inhibits this enzyme. However, where the brain has become insulin resistant, this process is no longer inhibited.
Brain Atrophy in the Hippocampus
The accumulation of these plaques and tangles is then followed by atrophy of the brain’s tissue, usually beginning in the hippocampus. The hippocampus is the part of the brain responsible for short-term memory and for the transference of information from short to long-term memory.
Dr Nick Bryan from the University of Pennsylvania undertook a study which showed that patients with type 2 diabetes displayed increased brain atrophy and that this correlated with how long they had the condition.
He is quoted on the ‘University Herald’ Website as stating: “Diabetes duration correlated primarily with brain atrophy, stated another way, our results suggested that, for every 10 years of diabetes duration, the brain of a patient with diabetes looks approximately two years older than that of a non-diabetic person, in terms of grey matter volume.”
Treating ‘Type 3 Diabetes’ and Insulin Resistance
Knowing that insulin resistance has such a central role in the pathology of Alzheimer’s disease should, in theory at least, mean that this can be avoided.
Alzheimer’s disease carries a similar level of fear and concern to cancer and heart conditions, often instilling a feeling of hopelessness. However, when one considers that Alzheimer’s disease can be prevented through dietary and lifestyle changes, a person can become empowered to take control of their own health and wellbeing.
Becca Levy, an Associate Professor of Public Health at Yale School has conducted research around how negative thoughts around aging could in fact be a main cause of the pathological brain changes that are commonly linked to Alzheimer’s.
ScienceDaily covered Professor Levy’s research in a recent article, stating that “participants [in the study] holding more negative beliefs about aging had a significantly greater number of plaques and tangles.” These are, of course, two of the primary pathological features of Alzheimer’s disease.
Professor Levy’s study highlights the centrality of ‘self-empowerment’ to effectively managing one’s own health. It is important to realize that aging is not a disease in itself and that Alzheimer’s can be prevented and, in some cases, even reversed by undertaking considerable changes in diet and lifestyle.
Diet is especially important here, as it is for the avoidance of any condition. The majority of insulin-resistant people have developed this condition from eating large quantities of refined, processed carbohydrates. Diets which are rich in nutrient dense wholefoods are able to help avoid the development of such conditions. Key dietary considerations include:
Vegetables should make up at least half the plate at both lunch and dinner, ideally including some at breakfast as well. The average person should aim to eat between 6-8 portions of vegetables each day.
Low GI fruits should be consumed wherever possible. These include pears, berries, apples and plums. Up to one to two portions per day.
It is important to avoid fizzy drinks, fruit juices, biscuits, cakes and white rice. Starchy carbohydrates which should be eaten include sweet potatoes, beetroot and carrots.
Healthier fats include oily fish, extra virgin olive oil, coconut oil, seeds, nuts, avocado and small amounts of butter. Fats to avoid include corn oil, sunflower oil, fried foods, pastries and processed meats. The brain is made up of 60% fat so including adequate amounts is important.
Medium Chain Triglycerides (MCT’s) are a naturally occurring source of dietary fat that are present in coconut and palm oil. MCT’s such as coconut oil may also provide nourishment for the brain, in particular, if a person is insulin resistant and the brain does not have access to an adequate level of glucose.
Without rapid cultural and dietary changes, it is possible that Alzheimer’s disease – or type 3 diabetes – could become the world’s next epidemic as the amount of people suffering from the disease continues to increase and healthcare provision struggles to manage this.
However, a proactive stance on health, a healthier diet and a healthier lifestyle can help address this problem on a large scale.
Alzheimer’s disease is a complex condition which is impossible to explore thoroughly in just one article, and this piece has considered just one of a multitude of causative factors. However, both glucose metabolism and insulin resistance clearly demonstrate just two factors of Alzheimer’s disease that can be prevented and even reversed via lifestyle and dietary changes. With this in mind, it is possible that Alzheimer’s disease could be a completely preventable condition.
References are available on request.
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