Expert reveal why cancer survivors are less likely to develop dementia

It’s a medical mystery which has puzzled scientists for decades – why are people who survive cancer much less likely to develop dementia later in life?

A number of studies over the past 20 years or so have found that a cancer diagnosis (of almost any type of cancer) reduces the risk of dementia by around 25 per cent.

Now researchers think they may have discovered the secret to this unusual link between two of the world’s biggest killers. Scientists at Huazhong University of Science and Technology in China have identified a key protein – called cystatin C – which is released by cancer cells as a by-product of tumour growth.

The research, published in the journal Cell, shows this protein is able to cross the blood-brain barrier, the protective chain of cells that blocks access to anything potentially harmful.

Once inside the brain, cystatin C appears to trigger a reaction that destroys the clumps of abnormal protein (called amyloid plaques), which are linked to the development of dementia.

The findings come from animal studies and it’s not certain yet whether the same process happens in humans.

But the research could provide vital clues in the search for new and effective dementia treatments, says Elio Riboli, a professor of cancer epidemiology and prevention at Imperial College London, who has spent years studying this crucial interaction between cancer and dementia.

‘This is very interesting research and it might explain one of the mechanisms behind why cancer survivors seem to have a lower risk of dementia,’ says Professor Riboli.

‘It could lead to the development of new drugs [for dementia] that increase this protein and potentially prevent it.’

Around 900,000 people in the UK are living with dementia and it kills more than cancer or heart disease – about 75,000 a year – usually from problems arising from a weakened immune system, such as pneumonia or difficulty swallowing.

Current drug treatments include cholinesterase inhibitors (e.g. Aricept), which work by boosting the activity of acetylcholine – a chemical in the brain vital for memory and learning.

But while these can ease symptoms and improve quality of life, they’re not a cure. Newer drugs, such as lecanemab and donanemab, slow down the progression of the disease in the early stages when symptoms have started to appear.

But they are not approved on the NHS due to their cost, limited effect and potential side-effects, including brain bleeds.

Finding out why cancer might stop some people getting dementia in the first place could be vital in the search for better medications.

Cancer survivors – especially those who get cancer in childhood – tend to have shorter lifespans (often because of the toxic effects on major organs caused by treatments such as chemotherapy), so some people might not live long enough to develop dementia.

And people who survive cancer may be generally healthier – eating sensibly, exercising regularly and limiting alcohol intake – making them less likely to get dementia.

But most studies take account of these confounding factors, and have still found cancer reduced the dangers.

The latest research began with scientists transplanting human lung, prostate and bowel cancer samples into mice that were genetically bred to be at a high risk of dementia.

None of the mice developed the brain plaques linked to the condition.

The team then spent several years trying to pinpoint which of the thousands of proteins released by cancer cells was having this protective effect. They eventually whittled it down to one: cystatin C.

During subsequent tests, the research team found cystatin C binds to brain plaques – this then activates immune cells in the brain to launch an attack which breaks up the plaques.

Mice with dementia-like deposits that were injected with the cystatin C protein showed improvements in memory and learning. Further studies are now planned.

Cystatin C is not the only cancer-based protein that has shown promise in warding off dementia.

A team of scientists at Bristol University is currently investigating the role of PIN1 – a protein released by cancer cells to stimulate further tumour development and growth.

Their research suggests that the more active the PIN1 protein is in driving cancer growth, the more protected the brain is against cognitive failure linked to amyloid plaques. It also has a similar effect on tau, another protein that accumulates in brain cells and that’s linked to dementia.

Meanwhile, the same Bristol team is investigating whether another molecule – an enzyme called PI3K – may be a factor in reducing dementia risk.

In cancer, this enzyme is highly active – aiding the proliferation of malignant cells and helping the disease spread.

But in dementia patients who haven’t had cancer, its activity is dialled right down.

It is believed that cancer stimulates the activity of PI3K and this then protects the brain against dementia later on by preventing deposit formation.

Meanwhile, there is also evidence that people who develop dementia are unlikely to then get cancer.

A 2017 study in Taiwan, ­published in the journal Neuropsychiatry, looked at 25,000 patients with Alzheimer’s disease and found they were nearly 20 per cent less likely to develop any form of cancer than those without dementia.

Other studies put the reduction in cancer risk as high as 60 per cent.

The theory is the destruction of brain cells that occurs with dementia means those same enzymes that would promote cancer growth are being heavily suppressed.

Professor Riboli warns it may not be as simple as finding one cancer-secreted protein to stop dementia in its tracks.

‘Cystatin C cannot be the only one and indeed it may not even be the main one,’ he says.

‘But this new study has shown that they [cancer proteins] may have a powerful protective effect against the formation of amyloid plaques.’