Alzheimer’s, dementia and diabetes

Alzheimer’s disease and diabetes are both increasing in numbers. Dr Louise Johnson explains why the associations are getting stronger with better data.

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Alzheimer’s disease

Alzheimer’s disease was diagnosed by German psychiatrist, Professor Alois Alzheimer, in 1906. Alzheimer’s disease is the most prevalent form of dementia in the aging population. Recently declared as the sixth major cause of death in the world.

Patients affected with Alzheimer’s suffer a gradual decline of cognitive abilities and memory functions till the disease renders them incapable of performing normal daily activities, such as eating, dressing and bathing.

Over 30 million people suffer from Alzheimer’s disease in the world. And this number is estimated to double to 60 million by 2030.²

Clinically Alzheimer’s disease (AD) can be classified into two sub-types: Late-onset or sporadic AD and early-onset or familial AD.

Late onset AD

This type affects about 95% of the Alzheimer population. These people are older than 65 years of age. Other than ageing, other risk factors for late onset AD are:

• Stroke
• Family history of diabetes
• Hypertension
• Obesity
• ApoE4 gene

Studies revealed that the apolipoprotein E (ApoE4) gene is a significant risk factor for the development of the disease.

Early onset AD

It affects 5% of the Alzheimer population. This disease is diagnosed in thirties, forties or fifties. It’s due to the mutation of three genes: amyloid precursor protein, presenilin-1 and presinilin -2.¹

Type 2 diabetes

Diabetes mellitus is a chronic metabolic disorder that is increasing worldwide. In 2019, there were 415 million people with diabetes worldwide. Of this number, 95% are Type 2 diabetes. There is another approximate 50% (220 million) walking around undiagnosed. Currently, one in every 11 people worldwide has diabetes according to the International Diabetes Federation 2019.

The salient features of Type 2 diabetes are:

• High levels of blood glucose
• High insulin levels
• Insulin resistance

Insulin resistance arises due to decrease insulin sensitivity in the muscle, fat tissue and liver.

What evidence proves there is link between diabetes and Alzheimer disease?

Epidemiology studies show that Type 2 diabetes increases the risk for AD by two-fold. Type 2 diabetes is strongly associated with late onset Alzheimer’s disease. This association is partially due to cerebrovascular disease (stroke and TIA). But that isn’t the only reason. The reason that the connection between these two major diseases can be made are:

• Insulin resistance
• Inflammation and blood vessel damage
• Blocked nerve communication
• Tangled tau proteins

Insulin resistance

When cells don’t utilise insulin the proper way, this can affect the brains mechanics. When your brain cells aren’t fuelled properly, the brain can’t function correctly, resulting in blood glucose to rise. Over time this can result in harmful fatty deposits in the blood vessels.

Having too much insulin can upset the chemical balance in the brain. The impact on the brain is so strong that Alzheimer’s disease related to insulin resistance should be referred to as Type 3 diabetes.

Inflammation and blood vessel damage

Those who have diabetes are at higher risk for heart attack and stroke. High blood glucose levels can cause bouts of inflammation, which puts stress on the blood vessels. Those damaged vessels can then result in Alzheimer’s disease. Inflammation can also make cells more insulin resistant. This is worse in obese people.

Blocked nerve communication

High blood glucose relates to high levels of beta amyloid, which is a protein that, when clumped together, can become stuck between the nerve cells in the brain and caused blocked signals. Nerve cells that fail to communicate are a big trait associated with Alzheimer’s disease.

Tangled tau protein

Your cells are always moving food and other supplies along pathways, akin to railroad tracks. A protein, referred to as tau, helps these tracks run in straight rows. In brains of Alzheimer patients, however, tau gets all tangled up, leading to falling apart tracks and dead cells. Some studies say those with diabetes have more tangles of tau protein in their brains, resulting in more dying cells in the brain, which as we know can lead to dementia.

How to reduce your risk?

1. Prevent diabetes or manage it effectively with the correct medication with the help of your doctor.
2. If you already have metabolic syndrome, weight loss and diet and exercise will help. Address your risk factor of high blood pressure and abnormal blood cholesterol with the correct prescribed tablets.
3. Eat healthy foods including vegetables, fruit, lean meats, whole grains and low-fat milk and cheese.
4. If you’re overweight, start a healthy diet and exercise to lose weight.
5. Exercise for at least 30 minutes five times a week.

Metabolic syndrome raises the risk of dementia in people under 60

Metabolic syndrome is defined by the presence of three of these risk factors:

• Impaired fasting glucose
• Waist circumference in a female more than 80cm and in a male more than 94cm
• High blood pressure above 130/85 mmHg
• Increased triglyceride cholesterol
• Low HDL cholesterol

In a recent study running over 20 years, the Whitehall II cohort showed that the risk of dementia is increased by 13% in people with metabolic syndrome younger than 60 years of age. In the age group between 60 and 70 years, the risk increase with 8%. The Whitehall II cohort consisted of UK civil servants: 10 000 in London (1991 to 2016).

The study concluded that the dementia risk was significantly high in study participant under age 60 years who had at least one metabolic syndrome component even when they didn’t have cardiovascular disease (heart attack or stroke)

Type 1 diabetes and Alzheimer’s disease

Most data have focused on Type 2 diabetes. It has been found that impaired learning, memory, problem solving, and mental flexibility have been found to be more common in patients with Type 1 diabetes than in the general population.

Treatment of Alzheimer’s disease

There is currently no treatment for Alzheimer’s, only drugs to slow down symptoms.

Pioglitazone

The diabetic drug, pioglitazone, improves insulin resistance and promotes cholesterol management by the liver. In 12 small studies of Type 2 diabetes with mild cognitive impairment, pioglitazone was promising in three studies. There was cognitive improvement.³

Intranasal insulin

Intranasal insulin enters the brain direct via the olfactory pathway. Participants who were treated with intranasal insulin showed greater improvement in memory and attention 21 days after start of treatment.

Alzheimer’s disease and diabetes are both increasing in numbers. The associations are getting stronger with better data. The best treatment currently is to manage glucose and other risk factors optimally.

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References

1. Dorszewska J, Prendecki M et. al. (2016) Molecular basis of familial and sporadic Alzheimers disease. Curr Alzheimer Res, 13, 952-963
2. James BD, Leurgans SE, Hebert l et. al.(2014) Contribution of Alzheimers disease to mortality in the United States. Neuroloy 82,1045-1050
3. Watson GS, Craft S.” The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment” CNS Drugs 2003;17:27-45

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