“It looked very compelling,” recalled Vissel this week. “I went home, immediately saw my doctor, and got the shingles vaccine after discussing it with her.”
Geldsetzer’s study, published in Nature on Wednesday, used data from Wales’ shingles vaccination program. Due to limited supply and the belief the vaccine was not as effective for people over 80, the Welsh rolled out the vaccine to people aged 79 in September 2013.
This created a perfect natural experiment to study the effect of vaccination on a group of people who have almost no differences except the week of their birth. Geldsetzer tracked dementia diagnoses for both groups over the next seven years, and found those who got jabbed had a 3.5 per cent lower risk of being diagnosed with the brain condition.
This masthead can also reveal the same team has similar Australian data from our shingles vaccine program, uploaded online but not yet peer reviewed, that shows a 2 per cent reduction in risk.
“If this is an added effect, it potentially has a really profound effect on public health,” said Dr Heidi Welberry, a biostatistician working on dementia prevention at the University of NSW.
But there’s a deeper and potentially more important story: the data suggests viruses may actually cause dementia (and Alzheimer’s, the most common type of dementia) – a new culprit, working alongside or even interacting with the amyloid-beta plaques that have long been drug companies’ focus.
“Amyloid-beta, we think, is just a reaction. It’s a distraction. We have to be focussing on the root cause,” said Griffith University’s Professor James St John, who published a call for more research on pathogens and Alzheimer’s in 2023.
This story has its start in 1991 in the Molecular Neurobiology Laboratory at the University of Manchester, when Ruth Itzhaki managed to painstakingly tease out DNA traces of the herpes simplex virus (the viral cousin of VZV, which causes chickenpox and shingles) from the brains of deceased Alzheimer’s patients, the first study to “show definitively the presence of a microbe in so-called sterile brain,” she told this masthead.
Ruth Itzhaki, a neuropathologist visiting professor at Oxford University and emeritus professor at the University of Manchester.
Her “heretical” work was greeted, she has written, “with much hostility”. The Amyloid Hypothesis, which argues Alzheimer’s is caused by the accumulation of amyloid-beta plaques in the brain that gum up its workings, was ascendant.
“The traditional researchers have gone ‘amyloid is causing this’,” said Associate Professor Catherine Butler, a microbiologist who studies the link between microbes and Alzheimer’s at the University of Melbourne. “But there have been so many failed drug trials, so many promising interventions which have not led to anything, really.”
Other scientists couldn’t believe a virus could lie dormant in the brain, cause no symptoms, yet somehow lead to long-term neurodegeneration.
But the viruses of Herpesviridae are wily and have been co-evolving with humans for 3 million years.
When we first catch VZV in childhood it causes chickenpox’s characteristic blistering rash – painful, but receding. The virus recedes too, entering into the nerves and then crawling back and up toward the spinal cord.
Our nerve cells are fragile and precious and so get a hall pass from the patrolling immune system. Thus concealed, VZV can remain in the body for decades.
The virus is designed to periodically reactivate. When we are young and healthy, our immune system quickly beats it back and we are none the wiser.
But as we age, and our immune system becomes less sharply honed, the virus can return with force and start killing nerve cells – provoking a dramatic immune response that can inflame an entire nerve-root. That’s what causes shingles, a condition so painful pain specialists describe it as “the ultimate neuropathic pain”.
Mandy Hawtin got the shingles vaccine as soon as she turned 50.
“I’d had four friends who’d had shingles over a couple of years. One was still in her 30s,” said Mandy Hawtin, 51, of Somerton Park. “Two of them had it for months, they were in pain, they had a terrible painful rash.”
She got the shingles vaccine as soon as she turned 50, hoping to prevent the painful condition. Now she’s hopeful that it will also reduce her chances of getting dementia.
But where does dementia fit in? Here’s one theory: VZV infiltrates the brain much as it does the rest of the body. As our immune system weakens with age, it is able to regularly reactivate within the brain (indeed, shingles tends to strike in our ’60s, the age when most scientists think Alzheimer’s pathology begins).
These neural reactivations are symptomless. But inside the brain, they lead to long-term increase in immune system activation, which in turn causes inflammation. A series of new studies within the last decade have shown this inflammatory response can actually lead to a build-up of amyloid-beta plaques.
What looked like a cause may actually be a symptom.
“If you’re having infections all the time throughout your life, you can get small-level increases of beta-amyloid which gets worse and worse,” said St John. “By the time you’re 65, you’ve got so much of this stuff around your brain just stops working properly.”
All that remains speculation – as does the reason the shingles vaccine might offer protection against dementia. Perhaps by better arming the immune system against shingles, there is less reactivation in the brain and therefore less inflammation.
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Or perhaps the vaccine provides a general system-wide boost to the immune system; this may explain why women, who typically get more of a boost from vaccination than men, saw better protection from dementia after the shingles jab.
As always, more research needs to be done – with some scientists now looking to an ongoing American trial of antivirals against dementia with great excitement.
Regardless of whether the link between herpes and dementia holds, the shingles vaccine remains a powerful defence (91 per cent efficacy in people aged over 70) against a nasty illness. And now there’s the potential for a little extra protection – though before making any health decisions, be sure to speak to your doctor.
“I am thrilled to hear that – we lost a family member last month to dementia. It’s certainly prevalent in my husband’s side of the family,” said Mandy Hawtin, after learning of the potential added defence. “So I’m going to be telling him to go get it right now.”
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