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 per cent less likely to develop dementia over the next seven years than those who did not receive the vaccine.
The findings, published Wednesday in the journal 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,” 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.”
Riverview Health Centre, a Winnipeg hospital that is home to long-term patients, has created a space where patients with Alzheimer’s and dementia relive memories with objects from their past, such as a vintage salon hair dryer and an office space with an antique typewriter. They also have a sensory room, a woodworking shop and a nursery.
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.
Randomized 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, Geldsetzer and his colleagues relied on a large, “natural” experiment that could help them answer the question in a similar way to a randomized 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 Sept. 1, 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,” 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 per cent less likely to get dementia overall, and 20 per cent less likely to than those who weren’t vaccinated.
“It was a really striking finding,” Geldsetzer said.
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,” said Perminder Sachdev, a UNSW neuropsychiatrist who focuses on dementia and was not involved in the study.
“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.
Studying vaccine benefits
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,” 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.
Canada, the U.K., U.S. and Australia currently all recommend a different vaccine called Shingrix, which uses different technology, and is significantly more effective at protecting against shingles.
“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,” said Henry Brodaty, co-director of the Centre for Healthy Brain Ageing at UNSW and who was not involved in the study.
“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 U.S. 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.
While there’s no proven prevention for dementia, doctors also recommend other common-sense steps to lower the risk. Stay socially and cognitively active. And control high blood pressure and, for people with diabetes, high blood sugar, both of which are linked to cognitive decline.
