Diabetes significantly increases the risk of developing dementia

Here, Dr Deborah Lee, Dr Fox Online Pharmacy, explores the link between diabetes and the increased risk of developing dementia

In 2013, the journal Diabetes and Investigation published a large meta-analysis of 28 observational studies.  The authors concluded that diabetes increased the risk of all types of dementia by 73%, Alzheimer’s Disease by 56%, and vascular dementia by 127%.

• Why should diabetes increase the risk of dementia?
• How does diabetes increase the risk?
• How can this risk be prevented?

Read on as I describe the key points about diabetes and dementia,  then explain the biochemistry as simply as possible, and outline the steps you can take to reduce your risk of developing both these devastating medical conditions.

What is diabetes?

Diabetes is a long term medical condition in which your body can no longer control the level of blood glucose.

When things are working normally, your blood glucose levels rise after eating. This triggers the release of the hormone, insulin. Insulin facilitates the uptake of glucose inside your cells, where it is needed as energy for metabolic functions. As a result, your blood glucose levels fall back within the normal range.

When you develop diabetes, your blood glucose control mechanism is no longer working properly.

Type-2 diabetes

In type-2 diabetes, your cells have become resistant to the effects of insulin and cannot take up glucose efficiently.

Type-1 diabetes

In type-1 diabetes, your pancreas is producing less insulin than you need. This is most often due to the presence of pancreatic antibodies. Type-1 diabetes is an autoimmune disease.

90% of people with diabetes have type-2 diabetes. However, both type-1 and type-2 produce similar outcomes, as both types result in high blood sugars and high insulin levels.

Diabetes increases your risk of other medical conditions such as strokes, heart attacks, blindness, kidney failure, and limb amputations. The most important thing to understand if you have diabetes, is that managing diabetes well, will greatly reduce these risks. Make sure you understand the key points about your diet and diabetes.

Diabetes also increases the risk of another serious medical condition – and this is dementia.

Increasing prevalence of diabetes

4.6 million people are currently living with diabetes in the UK, according to the charity Diabetes UK.  Numbers of cases of diabetes have doubled in the past 20 years.

More than 1 million cases of diabetes in the UK remain undiagnosed.  Many people remain completely unaware of their diagnosis. Early symptoms may be vague and go unrecognised.

A further 12.3 million UK residents are currently at increased of diabetes because they possess specific risk factors. Many of these risk factors are modifiable, such as obesity, smoking, alcohol, and taking exercise.

What is dementia?

Dementia is a chronic medical condition in which patients develop disordered thinking, difficulties reasoning, and memory problems.  In due course, this causes interference with their daily activities. There are often speech and communication difficulties, troubles with problem-solving, and an overall deterioration in self-care.  As dementia sets in, many people often undergo personality changes. They may also become very emotional. Eventually, most people with dementia cannot look after themselves and need 24-hour care.

Causes of dementia

Dementia has a variety of causes.

• Alzheimer’s Disease (AD) is the most common and accounts for 60%-80% of cases and has a specific brain pathology.
• Dementia is also commonly caused by atherosclerosis – the deposition of fatty plaques in vessel walls – in the cerebral blood vessels. Atherosclerotic vessel walls are more prone to rupture or bleed, which results in brain injury. This is known as vascular dementia.
• There are other rare causes of dementia, for example, there may be an underlying genetic cause such as Huntingdon’s Chorea.

Prognosis of dementia

Once diagnosed with dementia, this is progressive and irreversible. Average life expectancy is around 3-11 years from diagnosis.

Dementia is now the major cause of death in the UK, over and above deaths from heart disease. Numbers of cases of dementia continue to rise. 850,000 people are currently living in the UK with dementia. This number will reach one million by 2025, and two million by 2050.

How to prevent dementia

Research suggests that a healthy diet and lifestyle with regular exercise can be reduce the risk of all types of dementia. Attention must also be paid to reducing the development of vascular dementia, and to manage stress and depression.

Why does diabetes increase the risk of dementia?

Diabetes affects many of the complex physiologic and metabolic pathways in your body.

High blood sugars and high insulin levels cause brain inflammation which results in neurodegeneration.

There are 4 key processes/factors involved –

1. Oxidative stress
2. Insulin resistance (IR)
3. Saturated fat
4. Excess advanced glycation products (AEGs)

Each of these is explained below.

1. Oxidative stress

In Alzheimer’s Disease, there are two characteristic, pathological findings –

• Plaques are deposited on the outside of brain neurons, made up of amyloid-beta protein, and
• Neurofibrillary tangles are created within the neurons themselves, which contain tau protein.

These changes occur largely due to oxidative stress.

What is oxidative stress?

Every day, your body breaks down oxygen, which it needs for all your metabolic and cellular processes. This is called oxidation. However, when oxygen is split into two atoms, molecules are produced called ‘reactive oxygen species’ (ROS) – or ‘free radicals.’

Free radicals are dangerous as they damage DNA, interrupt cell repair, and disrupt proteins. They are neutralised in the body by molecules called antioxidants.

Oxidative stress occurs when there is a relative imbalance in the body, with too many free radicals, and a deficiency of antioxidants.

Causes of oxidative stress?

There are many things which cause oxidative stress –

• A high intake of saturated fats – a diet rich in omega-6 fatty acids, and low in omega-3 fatty acids.
• A diet deficient in antioxidants – these are found in large quantities in fruit and vegetables, fresh foods, and natural ingredients.
• Smoking – produces large amounts of free radicals and reduces the effects of antioxidants.
• Stress – activates the hypothalamo-pituitary axis and increases the production of free radicals.
• Lack of sleep – disruption of circadian rhythms increases oxidative stress.
• Lack of exercise – exercise promotes antioxidant activity.
• Infections – chronic bacterial infections increase oxidative stress. For example, H.pylori, a common cause of gastritis and peptic ulcers, C. pneumoniae, which causes community-acquired pneumonia, and P.gingivalis which causes periodontitis.
• Environmental pollutants – for example, pollution, pesticides and radiation.

 Oxidative stress and neurodegeneration

Oxidative stress is very damaging to the human brain.

• Fat breakdown – 60% of the human brain is composed of fat. The myelin sheath of neurons is made up of polyunsaturated fatty acids and cholesterol. Brain phospholipids are very vulnerable to oxidative stress. Neuronal health is vital for nerve transmission and cognitive function.

Lipid peroxidation (fat breakdown) produces free radicals which trigger the process of neurodegeneration, resulting in increased amyloid-beta deposition and the production of neurofibrillary tangles.

• Brain biometals – Oxidative stress may also disrupt the normal function of brain biometals such as copper, iron, and zinc.
• DNA damage – Free radicals within brain tissue directly damage DNA, breaking strands and causing DNA-protein cross-linkage.

2. Insulin resistance

What is insulin resistance (IR)?

Diabetes and AD are both associated with insulin resistance. Insulin resistance occurs when cells in your body become less sensitive to the hormone insulin. This metabolic condition gradually develops over a gradual period.

When insulin resistance has set in, your pancreas is having to produce extra insulin to keep your blood glucose levels normal.

As insulin resistance worsens, you may then pass into the stage of prediabetes. At this stage, your pancreas is failing to keep up with the demand for insulin. As a result, your blood levels of glucose become elevated, but your cells are relatively starved of glucose.

The next step is the development of full-blown diabetes. However, insulin resistance and prediabetes are potentially reversible.

Causes of insulin resistance

IR develops with increasing age and is associated with obesity, smoking, lack of exercise, high blood pressure, and sleep disorders.

How to get diagnosed with insulin resistance

Diagnosing insulin resistance is not easy. You will need to take medical advice.

IR is more likely if your abdominal circumference measures over 32 inches for a female, or 40 inches for a male.

IR often occurs as part of metabolic syndrome.

 Heath risks of insulin resistance

Insulin resistance is dangerous because it increases many health risks.

For example, IR doubles your risk of a heart attack or a stroke. It also trebles your risk that if these occur, they will be fatal. IR also increases your risk of many cancers.

Oncologists believe that obesity and insulin resistance play a role in the development of cancers such as breast and colon cancer.

Reversing insulin resistance?

It’s important to recognise if you have insulin resistance, or metabolic syndrome because you can take steps to reverse them.

Losing weight can have impressive results. In one study a loss of 10% of body weight led to an 80% improvement in insulin sensitivity. This means by losing weight, you can stop yourself developing full-blown diabetes.

Insulin resistance and dementia

Insulin resistance is one of the key underlying mechanisms causing dementia.

• IR disrupts cell-signalling – Brain function depends on cells signalling to each other using different chemical messengers. When IR is present, cell signalling is altered.
• Insulin degrading enzyme (IDE) – Insulin is broken down by an enzyme called insulin degrading enzyme (IDE). However, this enzyme also destroys amyloid-beta protein, which is deposited in Alzheimer’s Disease. When levels of insulin are high in the brain, IDE is in relatively short supply, with less availability to clear amyloid proteins.

3. Saturated fat

A high-fat diet, especially a diet rich in saturated fats, leads to brain inflammation.

Saturated fats are unhealthy fats found in butter, fatty meat, and cheese. Once ingested, these are broken down in the gut to form free fatty acids (FFAs). In the brain, the hypothalamus detects saturated FFAs and switches on IR.

Saturated FFAs in the brain results in –

• The release of cytokines – these proteins coordinate the immune response and cause inflammation but are harmful to nerve tissue. Examples include –
• TNF-α – a neurotoxin.
• Interleukin IL-1β – associated with the development of other brain diseases.
• Interleukin IL-6 – has a role in the destruction of nerve cells.
• Increased permeability of the blood-brain barrier (BBB) – allowing other toxins into the brain tissue.
• Stimulation of microglia – these are macrophages, cells involved in cell repair. The job of microglia is to identify dead nerve cells and phagocytose them (eat them up.) Brain inflammation stimulates the activation of microglia.

4. Advanced glycation end products (AEGs)

We are all at risk from substances called advanced glycation end products (AEGs). These are formed naturally either when we cook food, or by chance when molecules collide within the body.

AEG’s are formed when sugars such as glucose or fructose stick themselves to fat or protein molecules. More AEG’s are created as we age, and AEGs are generally bad for our health. AEGs are produced by cooking at high temperatures such as roasting, frying, barbecuing, or toasting.

When blood sugars are high, for example in diabetes and IR, this leads to an increase in the formation of AEGs.

AEGs are found in larger amounts in the brains of people with Alzheimer’s Disease.

Summary – the link between diabetes and dementia

In the UK, the increase in diabetes and dementia results from our Western lifestyle – notably,  a diet high in saturated fat, and lack of exercise. These factors, amongst others, lead to the development of oxidative stress and insulin resistance. This is then further compounded for example, by the formation of toxic AEGs.

Living with high blood glucose levels, and high insulin levels, with insulin resistance, prediabetes, and diabetes,  are major causes of neurodegeneration.

How to reduce the risk of dementia?

48.4% of cases of dementia are attributable to the following 7 risk factors  (World Alzheimer Report 2014).

• Smoking
• Midlife obesity
• Physical inactivity
• Low educational attainment
• Diabetes
• High blood pressure
• Major depression

Evidence suggests we may be able to reduce dementia by modifying these risk factors.

One of these risk factors is type -2 diabetes.

Dementia prevention

There are various aspects of health you may be able to improve that are likely to reduce your risk of dementia.

• Nutrition

The Mediterranean Diet (MD) has been shown to improve cognition, memory, and language.  in many randomised controlled trials. The diet is rich in fruits and vegetables, fish, and lean meats, and hence is rich in antioxidants, omega-3 fatty acids, and fibre.

The MIND diet is a carefully formulated diet which combines The Mediterranean Diet with the Dietary Approaches to Stop Hypertension Diet (DASH), and specifically includes nutrients for brain health.

A 2015 prospective American study compared 3 groups of older people living in residential care, each group following one of the diets – MD, DASH, or MIND for 4.5 years. The authors found that high adherence to all 3 diets reduced the risk of Alzheimer’s Disease. However, the best results were seen with the MIND diet. High adherence to the diet reduced the risk of Alzheimer’s Disease by 53%.

The authors believed strongly that correct nutrition has huge benefits for brain health.

• Weight loss

Weight loss and dementia – Most research seems to show that weight loss does reduce the risk of dementia, but that is mostly achieved by increasing levels of exercise. (WHO 2019).

Weight loss and diabetes – However, many studies have shown that weight loss does reduce the risk of diabetes.

For example, in a 2000 study of 618 people aged 30-50 who were overweight, there was a 37% reduction in the risk of diabetes in those who lost weight (8-15 pounds) and kept it off. The effects were strongest in those who were obese (BMI>29, and an even greater risk reduction for diabetes was seen for those who lost even larger amounts of weight.

One 2017 mathematical modelling study has predicted that 2 out of 5 cases of diabetes could be prevented if as a population, we could reduce the average BMI by 1-2  kg/m².

To do this would require an average weight loss of 3-6kg per person.

• Preventing diabetes

Find out your risk of developing diabetes at Diabetes UK

Click on the – Know Your Risk – tool.

You can take positive steps to reduce your risk of developing diabetes.

Prevention is always better than treatment.

• Exercise and cognition

Numerous studies have reported the benefits of exercise on cognition, and on reducing the risk of Alzheimer’s Disease.

The benefits of exercise for brain health are thought to be due to increased cerebral blood flow, increasing levels of endorphins, enhanced cell-signalling, and a reduction in the production of inflammatory cytokines.

• Reducing the risk of vascular dementia

The risk of vascular dementia can be reduced by good management of high blood pressure, reducing raised cholesterol levels, and optimal management of diabetes.

• Mental health

Much evidence links chronic stress with increased brain inflammation and impaired cognition. Chronic stress is also associated with increased amyloid-beta in the mouse brain. Depression is known to slow cognitive processes.

Treating depression, including the use of certain antidepressants, can substantially improve cognitive function. Further research is required to establish if treating these conditions reduce the risk of dementia.

• Smoking

For every 20 cigarettes smoked per day, your risk of dementia increase by 34%.

This was the conclusion of a huge 2015 meta-analysis of 37 studies.

However, here is the good news – the same study showed that quitting smoking reduced the risk of dementia to the level of never smokers.

Visit NHS Smokefree

Now has never been a better time to quit smoking.

You are three times more likely to succeed if you seek help.

Final thoughts

Both diabetes and dementia are devastating diseases. However, there is so much we can do for ourselves to improve our health and reduce the risk of these diseases. Neither diabetes nor dementia is an inevitable consequence of ageing.

What can you do to reduce your risk of diabetes, and dementia?

For more information

• Diabetes UK – Diabetes and Dementia
• Endocrine web – Type 2 diabetes: Tips to Lose Weight Successfully
• co.uk – Lifestyle Changes for Type-2 Diabetes