Shingles vaccine linked to reduction in dementia diagnoses, study finds

By Jacinta Bowler, ABC science reporter

The research was undertaken using the live shingles vaccine Zostavax, however that has now been replaced with the Shingrix vaccine.

• The shingles vaccine has been linked to lower dementia risk, according to a large study in Wales.
• Researchers say vaccination may have this effect by reducing reactivations of the virus that causes chickenpox and shingles, or through broader immunological effects.
• Experts suggest more direct research is needed to confirm why this is occurring, while the team of researchers are now looking at funding a large clinical trial.

Scientists may have produced the strongest evidence yet that the shingles vaccine is linked to reduced dementia risk.

Using the health records of more than 280,000 older adults in Wales, researchers found those who received the shingles vaccine were 20 percent less likely to develop dementia over the next seven years than those who did not receive the vaccine.

The findings, published today in Nature, build on other recent studies that have demonstrated associations between herpes virus infections and an increased risk of developing dementia.

Lead author Pascal Geldsetzer, from Stanford University, said the protective effects of the vaccine appeared to be "substantially larger" than those offered by existing dementia medications, but that further research was needed to determine if the observed effects were truly causal.

"If the shingles vaccine really prevents or delays dementia, then this would be a hugely important finding for clinical medicine, population health, and research into the causes of dementia," Dr Geldsetzer said.

According to the researchers, there are two potential mechanisms that might explain how the shingles vaccine could reduce the risk of dementia, and they may even work in tandem.

The first is that vaccination reduces reactivations of dormant varicella-zoster virus, which have been shown to cause long-lasting cognitive impairment and brain pathology akin to what is seen in Alzheimer's disease.

Varicella-zoster virus, a type of herpes virus, causes chickenpox and can linger in the body for years, later reactivating as shingles.

"There is a growing body of research showing that viruses that preferentially target your nervous system and hibernate in your nervous system for much of your life may be implicated in the development of dementia," Dr Geldsetzer said.

The second possible mechanism is that vaccination triggers a more widespread immune response.

Tissa Wijeratne, a neurologist at RMIT University and Western Health who was not involved in the research, said the study was a "landmark finding" in brain health and disease prevention.

"It supports the emerging understanding that infections - especially viruses like varicella-zoster - can contribute to long-term neurological decline."

An 'ingenious' natural experiment

While other studies have looked at the link between shingles vaccination and dementia risk, it has been difficult for researchers to disentangle the effects of the vaccine from the effects of other variables such as diet and exercise, which can also influence dementia risk.

Randomised controlled trials are considered the gold standard for studying causal relationships and can help to eliminate these biases, but they are exceptionally expensive and resource intensive, especially over such long periods.

To get around this, Dr Geldsetzer and his colleagues relied on a large, "natural" experiment that could help them answer the question in a similar way to a randomised controlled trial.

In 2013, Wales rolled out the shingles vaccine for older adults. But a quirk in the rollout meant that those who were 79 years old on 1 September, 2013 were eligible to receive the vaccine for at least one year, while those who had already turned 80 were ineligible for life.

"Just a one-week difference across this date-of-birth cut-off means that you go from essentially no-one getting vaccinated to about half of the population getting vaccinated," Dr Geldsetzer said.

Thanks to nationwide electronic health records, the researchers could look at almost the entire population of Wales born between September 1925 and September 1942 to see how vaccine status affected dementia risk.

They focused their analysis on people closest to either side of the vaccine eligibility threshold, so they were as close to the same age as possible.

Those who received the shingles vaccine were 3.5 percent less likely to get dementia overall, and 20 percent less likely to than those who weren't vaccinated.

"It was a really striking finding," Geldsetzer said.

"This huge protective signal was there, any which way you looked at the data."

The research team also investigated the impact of other variables, such as education levels and rates of other common health conditions, across both cohorts.

But they couldn't find any differences, aside from vaccination status, that would explain the staggering drop in dementia diagnoses.

"It is an ingenious use of record and linkage data," Perminder Sachdev, a UNSW neuropsychiatrist who focuses on dementia and was not involved in the study, Geldsetzer said.

"It is an example of the power of nationwide electronic records and the ability of researchers to link various health datasets."

The researchers also found similar results in a second population, using electronic health records and death from dementia data from England.

More research needed to understand vaccine effects

While the findings, if confirmed by further research, suggested vaccination could be an effective tool for preventing or delaying dementia, they also raised several questions.

To start, the study found dementia risk lowered significantly more in women than men.

This is not a finding unique to this study; other studies on shingles vaccination and dementia risk have also found that women seem to benefit from the vaccine more than men.

"We know that the effects of vaccines are stronger in women, and the immunological responses to vaccines are different in men and women," Professor Sachdev said.

"We need to learn more, including [about] sex differences in the pathogenesis of dementia in general."

Further studies were also needed to understand how vaccination might actually confer protection against dementia.

The research team looked specifically at the live herpes zoster vaccine - known as Zostavax - which was commonly used at the time.

The UK, US, New Zealand and Australia currently all recommend a different vaccine called Shingrix, which uses different technology, and is significantly more effective at protecting against shingles.

The vaccine is freely available in Australia to those over 65, and limited other groups.

"There has been evidence for some time that older people who receive their vaccinations in general are less likely to develop dementia. This is the best evidence yet to show this," Henry Brodaty, co-director of the Centre for Healthy Brain Ageing at UNSW and who was not involved in the study, said.

"Future research will determine whether the newer non-live vaccine Shingrix will provide the same benefit and whether immunisation at younger ages may be just as effective."

A large US study published last year found that Shingrix appeared to lower the risk of dementia even further than Zostavax.

The researchers of the current study, however, believe that the live nature of the Zostavax vaccine may have specific benefits for lowering dementia risk, and hope to fund further clinical trials investigating it.

- ABC