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It is described as the silent killer for good reason. With no outward signs or symptoms, cholesterol – a waxy, fatty substance in the blood – can build up slowly, clogging arteries and leading to potentially deadly heart attacks and strokes.
As many as six out of every ten adults in the UK are thought to have abnormally high levels – and most are completely unaware of it.
It is of particular concern that prevalence has risen sharply since the pandemic, following decades of decline. This is blamed on a drop in the number of people invited for NHS Health Checks, which measure cholesterol and are supposed to be given to everyone aged 40 to 74 every five years.
But decades of scientific research has revealed there is even further cause for alarm. High cholesterol – and particularly a type known as low-density lipoprotein (LDL) – is an integral part of the cascade of problems which eventually lead to dementia.
Studies that have tracked millions of people for decades have found that each small increase in the amount of LDL circulating in the blood is associated with an eight per cent increase in the risk of developing dementia in old age. And having persistently high levels can increase the risk by 33 per cent.
Significantly, the risk was greatest in mid-life – between the ages of 40 to 65 – suggesting that high cholesterol at this stage might set in motion a series of issues which result in dementia.
It’s undoubtedly a shocking development, but it offers a huge opportunity to tackle both heart disease and one of our most feared brain diseases at the same time.
Doctors say it's never too late to do something about your high cholesterol
Not only can high cholesterol be detected easily and cheaply in GP clinics or with self-testing kits, there are extremely effective ways of reducing it.
Several reviews of the best evidence have concluded that statins – drugs which lower cholesterol – may reduce the risk of dementia, and particularly Alzheimer’s, by up to one third.
Even cutting out unhealthy foods that include saturated fats, which are linked to high cholesterol, could reduce your risk.
One Danish study, which followed people for an average of 58 years, found those who did not follow healthy dietary guidelines were more likely to have high LDL and to develop some forms of dementia compared with those who did eat a balanced, healthy diet.
‘Adopting simple lifestyle changes to lower your cholesterol could have a huge impact on brain function and will inevitably delay or even completely prevent the onset of both dementia and heart disease later in life,’ says Dr Osman Shabir, an expert on the impact of cardiovascular disease on the brain at the University of Sheffield who works with both Alzheimer’s Research UK and the British Heart Foundation.
‘If your cholesterol is high, you can do something about it. Even if you’re in your 50s and 60s you can modify these risk factors. It’s never too late.’
The mechanism linking high cholesterol and vascular dementia, a form of the disease which occurs when blood flow is reduced to the brain, is well established. As we age, levels of cholesterol – which are mostly produced by the liver but which are also linked to a high-fat diet – rise in the blood.
Doctors are generally most concerned about levels of LDL – balls of fat and protein which carry cholesterol from the liver into the bloodstream and are often termed ‘bad’ cholesterol because they can clog up the arteries.
The body also produces high-density lipoprotein (HDL) – often termed ‘good’ cholesterol because it carries cholesterol away from the arteries and to the liver where it’s broken down and excreted.
Over time LDL can build up on, and harden, the walls of the arteries and lead to clots. These can break away and damage the blood brain barrier, a delicate layer of cells designed to protect the brain from clots and toxins.
‘This allows clots to enter the brain and cause strokes, reducing blood supply to parts of the brain and leading, in time, to vascular dementia,’ says Dr Owen Peters from the UK Dementia Research Institute.
And this relationship between cholesterol and Alzheimer’s is more complicated.
Alzheimer’s develops differently to vascular dementia, and is thought to be linked to the accumulation in the brain of toxic plaques called amyloid, and ‘tangles’ of proteins called tau. Some research has found having heart disease – including high cholesterol in the body – triples the amount of amyloid in the brain.
Dr Shabir says: ‘Brain cells stop being able to do their job properly, which is to clear amyloid. So you get more of it building up more quickly, which may increase the risk of Alzheimer’s.’
Also being researched is the relationship between genetic risk factors for Alzheimer’s and cholesterol levels inside the brain.
The brain makes its own supply of cholesterol, which is a key part of the structure of brain cells and communication between cells. But people who carry two copies of a gene called APOE4 – who are eight times more at risk of developing Alzheimer’s – have greater volumes of amyloid in their brains and also more LDL cholesterol, says Dr Peters.
Around two per cent of the population have two copies of this gene, which they inherit from their parents.
‘It isn’t clear whether this is linked to cholesterol from the body crossing a “leaky” blood brain barrier, or some other process going on inside the brain,’ he says. ‘The APOE4 gene is involved in cholesterol transportation in the brain, but we don’t know how it’s all linked. The relationship is very complicated, but it seems clear that cholesterol has some kind of role in Alzheimer’s.’
People with a different gene, APOE2, are protected against Alzheimer’s and they tend to have lower levels of cholesterol – adding to the evidence that cholesterol appears to be important.
Whatever the case, studies appear to show giving statins in mid-life can reduce dementia risk by a substantial amount.
These once-a-day pills, which reduce the amount of LDL produced by the liver, can lower levels by up to 50 per cent. They also reduce the risk of clots forming.
One analysis found that people who used a statin had a 32 per cent reduced risk of Alzheimer’s disease and a 20 per cent reduced risk of vascular dementia compared to people with untreated high cholesterol levels.
Some experts urge caution as these studies are observational only – showing an association over time – and some doubts about the theory still remain.
A review of the evidence by the respected Cochrane group of researchers found that statins given to people at risk of vascular disease did not prevent cognitive decline or dementia. However, the studies the team looked at gave statins to people in later life, when the damage caused by high cholesterol may have already set in motion the biological processes which lead to dementia. In other words, it may have been too late.
Despite the gaps in knowledge, experts agree that maintaining a healthy cholesterol level can only have benefits for overall wellbeing – whether that’s using statins, changing diet or becoming more active.
NHS guidance recommends cutting down on fatty foods, particularly those containing saturated fats found in butter, cheese, meat pies, fatty meats, cakes and biscuits.
Instead, eat more oily fish – such as mackerel and salmon – brown rice, wholegrain bread and pasta, nuts and seeds and fruit and vegetables.
One analysis of the evidence found diets high in tomatoes, flaxseeds, almonds, soy protein, avocados and high fibre or wholegrain foods caused ‘small to moderate’ reductions in LDL. Unfiltered coffee and sugar, however, caused an increase.
‘Adopting heart-healthy habits can have a profound effect on heart health but also brain health,’ says Ioanna Tzoulaki, professor of chronic disease epidemiology at Imperial College London. ‘That might be eating a healthy diet, exercising more and taking statins, if necessary, to reduce cholesterol.’
The Government must do more to ensure that all adults get their NHS Health Check, according to Alzheimer’s Research UK (ARUK).
The 30-minute appointment, which should be offered to everyone aged between 40 and 74 every five years, involves a number of tests for the early signs of life-threatening diseases.
Patients will typically get their height, weight and waist size measured, be given a blood pressure test, as well as a finger-prick blood test to check their cholesterol.
The doctor will then explain to the patient their risk of developing a serious condition such as heart disease, stroke or kidney disease.
However, data shows that just 56 per cent of men and 61 per cent of women take up the offer of an NHS Health Check. The number attending their check-up – likened to an MOT for the body – has also fallen over the past three decades. In 1998, 66 per cent of men and 67 per cent of women went through the tests.
Following the findings of the Lancet Commission’s research, the Health Check’s cholesterol test could now also be a key means of warning of the risk of developing dementia.
‘It is crucial to ensure that more people attend these vital appointments,’ says Samantha Benham-Hermetz, an executive director of ARUK.
‘It’s a win twice over, as keeping cholesterol at healthy levels not only decreases the risk of dementia, but also diabetes and heart problems.’