Could something as simple as getting a shingles jab significantly reduce your risk of dementia?
That’s the intriguing possibility raised by a growing body of scientific research, which points to common viruses as the true cause. Just last week researchers reported that people who’d had antivirals to treat another herpes virus, herpes simplex virus type 1 (HSV-1) which causes cold sores, had a lower risk of developing Alzheimer’s disease.
Much attention and funding for dementia has been spent on the idea that clumps of toxic proteins called amyloid cause Alzheimer’s – the most common type of dementia – by building up in the brain and damaging cells.
But what is causing them to build up is unclear.
Scientists are now pointing to low-grade viral infections as the culprit. And the hope is that using vaccines or antiviral drugs to quell these infections will fend off dementia.
One strain of herpes, the varicella zoster virus – which causes chickenpox in childhood and shingles in old age – is particularly in the spotlight as the virus can silently infect our brains and lie dormant for years.
Last year analysis of almost 400,000 people’s medical records from the UK and Australia showed that around a fifth of dementia cases might be prevented with a live shingles vaccine (Zostavax), reported the scientific journal Nature.
These findings were bolstered by an Oxford University study, also published in Nature last year, which found that a newer form of shingles vaccine, Shingrix, is more effective at preventing dementia and better at protecting against shingles.
Scientists are now pointing to low-grade viral infections as the cause of build-ups of toxic proteins called amyloid, which lead to Alzheimer’s. And the hope is that using vaccines or antiviral drugs to quell these infections will fend off dementia
The NHS offers shingles vaccines to everyone over 65 and people aged 50 and over with a severely weakened immune system. So how might viral infections cause dementia?
In the early 2000s, experiments showed that when lab-grown human brain cells are infected with the herpes virus, levels of harmful amyloid proteins inside them increased significantly. So it may be that the toxic protein clumps form as a normal response to viral infection.
A 2018 paper in the journal Neuron suggested that the brain might use amyloid as a first-line defence against infections, to capture viruses or bacteria and slow their spread before stronger immune responses kick in.
However, a virus such as herpes – which can remain dormant in nerve cells in the brain – might cause an overgrowth of amyloid which then leads to the toxic clumps seen in Alzheimer’s.
If this is the case, preventing the build-up could provide a more effective way to fend off dementia than current attempts to create drugs that remove proteins from the brain.
One such protein-removing drug – lecanemab – hit the headlines last year when the National Institute for Health and Care Excellence refused to approve it for use on the NHS because it deemed its benefits too modest to justify the huge costs involved in prescribing it. It also has worrying potential side effects such as brain swelling and bleeds.
An alternative approach – targeting infectious viruses – is gaining traction, though it is in fact decades old.
Ruth Itzhaki, a visiting professor of population ageing at Oxford University, has been working on this for almost 40 years, including publishing the pioneering lab studies of herpes-infected human brain cells in the early 2000s.
She became interested in the virus theory of dementia after reading about research that showed how both herpes-driven brain inflammation and Alzheimer’s affect the same regions of the brain, including the frontal lobes (which regulate thinking, emotions and memory) and the hippocampus (involved in forming memories). Her work has focused primarily on HSV-1, which causes cold sores.
Professor Itzhaki says HSV-1 is a strong candidate because ‘it is very common and you need something like that to explain the frequency of Alzheimer’s’.
She told Good Health: ‘Herpes has a tendency to go latent inside us and stay that way for a long time. As you get older your immune system becomes less effective, and so it may re-emerge as a brain infection. So far it looks like half the cases of Alzheimer’s may be caused by HSV-1.’
Professor Ruth Itzhaki became interested in the virus theory of dementia after reading how herpes-driven brain inflammation and Alzheimer’s affect the same regions of the brain
Other types of infections may be a risk factor because they cause brain inflammation that reactivates HSV-1.
‘People used to think that the brain was sterile,’ explains Professor Itzhaki, ‘but now we know there are viruses, bacteria and fungi in the brain. Gingivitis, chlamydia, fungi – all sorts of organisms have now been detected in brain tissue.’
In 2023, Professor Itzhaki founded the Alzheimer’s Pathobiome Initiative, a global group of scientists and entrepreneurs working on the viral brain infection theory.
Last year one of those involved, Dr Richard Lathe, an honorary professor in biomedical sciences at the University of Edinburgh, investigated post-mortem data from people with neurological illnesses, including dementia.
The investigation, published in the journal Brain, Behavior and Immunity Health, showed large amounts of infectious microbes such as the bacteria Streptococcus and Staphylococcus, as well as fungi such as Aspergillus and Candida – may have caused protein clumps to form, or prompted the reactivation of herpes virus, Dr Lathe told Good Health.
And such infections may become more dangerous as we get older, he adds: ‘From what we have seen, the number of microbes in the brain increases with age as our immune systems become less efficient – and this leads to all kinds of low-level infections.’
Dr Lathe believes that boosting the brain’s overall ability to kill off infections – with vaccines for example – may in itself help fend off dementia.
He points to around 20 reports in the past decade or so that have shown that vaccination reduces the risk of dementia.
‘Interestingly, it’s non-specific: it does not matter which vaccine you use – it can be against herpes, tuberculosis or pneumonia and meningitis,’ says Dr Lathe. ‘They all seem to inhibit Alzheimer’s to some extent.’
He adds: ‘It’s effectively about giving a jolt to the system – bolstering older people’s brain immune defences back into life.’
Dr Lathe believes that mass vaccination for these infections could offer our best hope for preventing dementia.
His preferred vaccine would be Shingrix, as it ‘contains adjuvants [a substance added to a vaccine to enhance the body’s response] to boost the immune system so that ageing people’s bodies have a better response to the vaccine – so it should act as an effective immune-system booster overall’.
Professor Itzhaki has a similar strategy, but suggests giving ageing people antiviral drugs.
A cold sore study, published last week in BMJ Open, found that people who’d had the virus had an 80 per cent increased risk of Alzheimer’s, but if they’d taken anti-virals to treat it, they were 17 per cent less likely to develop the disease.
‘Antivirals have few side effects,’ says Professor Itzhaki. ‘Dosing could be started in late middle age [rather like taking statins] which is when we think that the herpes virus gets into the brain.
‘Prevention is far better than treatment. Doing this is the only way ultimately that we would find out if this antiviral approach could save the lives of millions.’