• Study of people with Alzheimer’s found 81 per cent had diabetes or prediabetes
• Research found cheap diabetes drugs may be able to slow progress of disease
• The link between diabetes and Alzheimer’s was found by studying brain cells
• Prof Wharton said insulin resistance could be ‘targeted to improve brain health’

By JO MCFARLANE FOR THE MAIL ON SUNDAY

Not for nothing has type 2 diabetes been dubbed ‘a 21st Century epidemic’. Year after year, numbers continue to spiral upward. At the last count, one in ten Britons over 40 are living with a diagnosis – and this condition eats up a tenth of the annual £134billion NHS budget.

And, over the past decade, studies have revealed something even more alarming: scientists believe that the cascade of deadly problems which lead to type 2 diabetes – caused by too much body fat – may also lead to Alzheimer’s disease.

So strong are the associations between the two illnesses that some describe the incurable brain disease as ‘type 3 diabetes’.

One study of people with Alzheimer’s found 81 per cent had either diabetes or raised blood sugar levels, known as prediabetes, which puts them on the cusp of developing the full-blown condition.

But, shocking as this new twist is, it also offers a potentially game-changing opportunity to prevent the brain disease for the first time – by tackling type 2 diabetes early. And it opens the door to potential new treatments for dementia, too. Studies have found cheap diabetes drugs could be used for Alzheimer’s, and may even slow the progress of disease.

The science is still in its early stages, but it could be revolutionary because of the huge numbers it may benefit. At present, Alzheimer’s drugs only manage symptoms, and in a limited way slightly slow disease progression.

But researchers now think of dementia as part of the spectrum of illnesses linked to metabolic disease – an umbrella term often used to describe the triad of heart disease, high blood pressure and type 2 diabetes, which commonly occur together and are inextricably linked, each exacerbating the other.

That means, suddenly, there may be a more obvious way to prevent and treat it. And it could be as easy as losing weight and eating healthily.

‘Thinking about dementia as a metabolic disease shows a clear way forward,’ says Dr Ivan Koychev, senior clinical researcher in dementia at the University of Oxford. ‘While the term type 3 diabetes is a bit simplistic, there’s little doubt conditions such as diabetes make the dementia process worse.’

Dr Koychev is clear we can all take steps to mitigate this risk, and it is vital to think ahead. ‘Given the whole dementia process starts ten to 15 years before the first symptoms emerge, we need to start controlling these factors in middle age,’ he says

Prevent diabetes and metabolic disease and you might also prevent dementia.’

As Stephen Wharton, professor of neuropathology at Sheffield University, puts it: ‘So far we’ve focused on finding a cure for dementia, which is great. But another way of looking at it is to say, “Don’t have heart disease, high blood pressure, and diabetes. Instead, control your weight, don’t smoke and have a good diet.”’

The mechanism linking vascular dementia, a less common form of the disease that occurs due to problems with blood flow to the brain, and metabolic disease, including diabetes, is well established. High blood pressure, which often features with these conditions, places more force on the artery walls, making them stiff.

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This makes it hard for oxygen-rich blood to flow freely through the small blood vessels into the brain. If brain cells receive fewer essential nutrients, they eventually die off, causing problems with memory and normal thinking. Blockages can also trigger mini-strokes, causing further damage.

The link between diabetes and Alzheimer’s, however, was found by studying brain cells. To understand this, it’s important to understand how type 2 diabetes works.

In those who suffer from the condition, it’s believed that weight gain and inactivity leads to fat accumulating in the liver and pancreas. This, in turn, affects production of the hormone insulin.

Normally, when we eat foods containing carbohydrates, they’re broken down into single molecules of sugar – usually glucose – during digestion and these molecules are absorbed into the blood.

At the same time, insulin is released by the pancreas, and the hormone helps move glucose from the blood and into cells, where it’s used for energy. But fat in the liver blocks the signalling that leads to the release of insulin and, without sufficient insulin, the body’s cells can’t take up glucose.

This leads to dangerously high levels of sugar in the blood, which over time causes damage to the heart and other organs.

The body pumps out more insulin from the pancreas to compensate, and this can also cause damage.

In people with Alzheimer’s, tests showed their brain cells were resistant to insulin. In the brain, if the cells can’t take up glucose they can’t communicate properly and die – which leads directly to problems with memory and thinking.

But excess insulin, as is found in those with type 2 diabetes, may also reduce the amount of an enzyme in the brain responsible for controlling a substance called amyloid in the body. Amyloid can flow naturally through the body. But less of the enzyme means more amyloid accumulates, causing it to become sticky and form clumps. In the brain, these clumps, known as plaques, interfere with brain function and ultimately, scientists believe, lead to irreversible damage and Alzheimer’s.

‘If you mess around with your body’s insulin levels, which is what happens with type 2 diabetes, you could be influencing the ability of the brain to clear amyloid,’ says Professor Tara Spires-Jones, of the UK Dementia Research Institute at The University of Edinburgh.

Specialist scanning techniques show that even before symptoms of dementia appear, those with type 2 diabetes already have insulin resistance in their brain cells.

Mum had diabetes then dementia… I don’t want to suffer the same fate
Sophia Husbands’ mum Caroline developed type 2 diabetes in her late 50s.

‘She said to us, firmly, “This stops here,” ’ Sophia recalls. ‘She’d watched her mum, Janey, suffer a stroke after living with type 2 diabetes and high blood pressure.’

Caroline had taken her diabetes diagnosis seriously. She had gained weight after having children but she transformed her diet, cutting back on salt and baking instead of frying. She was adamant her children shouldn’t suffer the same fate.

But now, just a few decades on, Caroline, 75, has symptoms which point to dementia. She is set to have tests. It is all the more painful for Sophia, 41, from Slough, Berkshire, as her father, Wilson, died with Alzheimer’s 14 years ago. ‘It was very hard – we were very close. He didn’t know who I was.’

Sophia began noticing changes in her mother’s behaviour a few years ago. ‘She didn’t seem like herself, and would say things which were out of character.’

Now Caroline can get disorientated and doesn’t always understand what is going on.

Whether Caroline’s type 2 diabetes led to her symptoms, Sophia will never know for sure, but she is determined to listen to her mother’s words.

Sophia, who runs wellness brand Love Happy Body, has overhauled her diet and lost the weight she had piled on during her 30s. She says: ‘With my family history, I know I’m more at risk from type 2 diabetes. It’s hard not to look at my parents and see my future, but there are things I can do to prevent it.’

Dr Koychev says: ‘These studies show that the higher the person’s blood sugar level, the worse their brain uses glucose. If there’s a part of the brain where there isn’t much glucose uptake, we know there’s potentially something wrong.’

This same effect has also been observed in the scans of those with Alzheimer’s and other forms of dementia.

Scientists can match up the area of the brain affected by this insulin resistance with the way dementia manifests itself in an individual’s behaviour of symptoms. It can be seen if a person’s memory, speech and language comprehension or movement is more affected.

But what remains unclear is precisely how insulin resistance develops in the brain and whether type 2 diabetes causes it.

The science is still being investigated – with the complicated truth being that not everyone with type 2 diabetes will develop Alzheimer’s, and not everyone with Alzheimer’s has diabetes.

‘It’s a bit of a chicken and egg question,’ says Prof Wharton. ‘Does Alzheimer’s cause insulin resistance in the brain, which might lead to more plaques? Or does type 2 diabetes cause insulin resistance in brain cells, contributing to more plaques and ultimately Alzheimer’s? These are difficult questions to untangle and both statements may have truth.

‘Either way, it seems insulin resistance is important and could be targeted to improve brain health.’

More compelling evidence comes from animal studies which show having type 2 diabetes gave them more plaques in the brain and worse memory problems. But treating their diabetes meant their condition improved. The Spanish researchers said this meant that detecting diabetes early, and treating it, ‘could slow or delay progression of Alzheimer’s’.

There could also be a genetic link. Around one in five of us carry the APOE4 gene, thought to be linked to half of all cases of Alzheimer’s. Most have no idea unless they have a genetic test.

A study by neuroscientist Dr Guojun Bu, professor of medicine at the Mayo Clinic in the US, found mice with APOE4 were more likely to have insulin resistance in the brain. And feeding them a high-fat diet to give them type 2 diabetes accelerated the brain damaging process in middle-age.

‘So, rather than in old age, it’s in middle age – when you have type 2 diabetes – that you begin to develop this brain problem,’ Dr Bu says.

There is cautious optimism that drugs used for diabetes could offer hope to those at risk of Alzheimer’s and other forms of dementia. But the evidence remains mixed.

One of the key things to tease out is whether the drugs areakving a direct effect on the progress of dementia, or simply controlling any underlying diabetes, and in turn having an impact on overall health. Scientists increasingly believe the former is most likely.

One major study found people with diabetes who took blood-sugar lowering drug metformin were less likely to develop any form of dementia compared with diabetes patients who did not.

A Taiwanese study also found the drug pioglitazone – which makes the body more sensitive to its own insulin – ‘significantly’ reduced the rate of dementia by around 44 per cent compared with those taking a different diabetes drug, sulfonylurea, which increases the amount of insulin released by the pancreas.

Dr Koychev said: ‘You could give the drugs early to protect against damage, even before people have dementia symptoms.’

Scientists are also trialling a nasal insulin spray to boost insulin to the brain, with mixed results.

There is also some evidence that weight loss alone can lead to type 2 diabetes remission.

A team led by Prof Roy Taylor at Newcastle University put overweight type 2 diabetes patients on a very low-calorie diet. Those who lost two stone or more, and kept the weight off, had normal blood sugar levels and no longer needed diabetes drugs two years on.

But, as with all diets, less than half of patients managed this, even with supervision and support.

Despite this, experts agree tackling obesity and type 2 diabetes, by whatever method, will undoubtedly reap huge health benefits – and may even prevent dementia.

With so much research into this area, what it offers now, for the first time, is hope.

Blood pressure pills and statins may reduce risk
One of the most important studies on dementia suggests lowering blood pressure drastically reduces the risk of the brain disease.

The Sprint Mind study found people with a history of hypertension – persistently high blood pressure – who brought down their readings ‘significantly’ reduced the risk of dementia or cognitive decline over four years.

Hypertension is incredibly common: one in three men, and one in four women suffer with it. But millions go undiagnosed as it causes few, if any, symptoms. And a third of patients who are diagnosed don’t manage to get their blood pressure down, even with medical advice.