Shingles vaccines may reduce dementia risk, two large new studies suggest

An estimated 98% of US adults have had chickenpox and are at risk for shingles; both are caused by the varicella-zoster virus, which is in the herpes family.

Herpes viruses are wily and can stow away quietly in the roots of nerves. They can reactivate during periods of stress or illness, or any time a person’s immunity is lowered. That viral reactivation can cause shingles, a rash that opens in a line around the trunk or down the neck or face. The pain from shingles varies from person to person but can range from tingling to searing, and it can go on for weeks.

Increasingly, researchers believe that some kinds of herpes viruses can also hide out in the brain and become active again when the immune system drops its guard. When they do, the theory goes, it may cause damage that promotes the development of dementia.

There’s no cure for shingles, but antiviral drugs can help treat it, and there are vaccines. In 2006, the first vaccine for shingles was licensed in the United States, Zostavax. In 2017, a stronger vaccine, Shingrix, became available. The US Centers for Disease Control and Prevention nowrecommends Shingrix over Zostavax for adults 50 and older.

Zostavax contained a live but weakened form of the virus, but Shingrix contains only part of it: proteins that sit on its outer surface. Both vaccines work by teaching the body to recognize and fight off the real virus when it begins to cause trouble.

In clinical trials, Shingrix was 97% effective at preventing shingles, compared with 65% to 70% effectiveness for Zostavax, depending on a person’s age. Shingrix also appears to give longer protection, although that’s still under study.

The two new studies make use of this history, looking back over the medical records of hundreds of thousands of people who were vaccinated with Shingrix and comparing how frequently they were diagnosed with dementia versus people who got other kinds of vaccines.

It’s difficult to eliminate all bias from observational studies like these, but the researchers tried to avoid one in particular: the healthy user effect. This holds that certain people — ones who are more likely to take care of their health — are also more likely to engage in a range of behaviors like going to the doctor regularly, exercising and getting vaccines. By the same token, people who are unvaccinated may be those who are too frail or sick to be vaccinated, or they may not have access to regular health care.

It’s that pattern of behaviors or personal circumstances, more than any one specific thing, that determines an individual’s risk for a number of diseases. If researchers try to compare vaccinated people with those who are unvaccinated, they run the risk of comparing two fundamentally different groups of people and falsely attributing any differences to vaccination alone.

Could a vaccine delay dementia?

The first study, which was published Thursday by the journal Nature Medicine, looked at dementia diagnoses in more than 100,000 people over 65 who got the Zostavax vaccine with about 100,000 65-and-older adults who got the Shingrix vaccine.

One of the study authors, an immunologist, is a paid consultant for GlaxoSmithKline or GSK, the company that makes the Shingrix vaccine, but the researchers say the company played no role in their investigation.

“Indeed, they didn’t even know we’d done it until the paper was accepted for publication, because we wanted to go out of our way to try and avoid any potential conflict,” said study author Dr. Paul Harrison, a psychiatrist at the University of Oxford in the UK, who spoke at a media briefing.

The researchers found that people who got Shingrix had a 17% lower chance of being diagnosed with dementia in the six years after their shots than people who got the less-effective Zostavax vaccine.

People who were vaccinated didn’t avoid dementia completely, but it did seem to be associated with a delayed diagnosis. On average, the researchers said, this represents about 164 diagnosis-free days, or about five months more time, in people who were eventually affected.

This kind of study can’t prove that the vaccines were directly responsible for the differences between groups. If further research proves that shingles vaccines do protect memory and thinking, “at a public health levelthat would be not a trivial finding whatsoever,” Harrison said.

Experts who were not involved in the study said it adds to a growing body of evidence that suggests shingles vaccines may help protect the brain.

“There was already some evidence that the old live vaccine was able to reduce the risk of Alzheimer’s Disease,” Dr. Andrew Doig, a biochemist at the University of Manchester, said in written comments.

It looks like the newer vaccine may be linked an even larger reduction in risk, he says.

“This is a significant result, comparable in effectiveness to the recent antibody drugs for Alzheimer’sDisease,” Doig said.

The association was stronger in women who got Shingrix, although it’s not clear why. Women had a 22% lower risk of developing dementia within the next six years compared with women who got Zostavax. Men had about a 13% lower risk.

The team next compared seniors who got Shingrix vaccine with those who got vaccinated against the flu and the combination of diptheria-pertussis-tetanus. The risk of dementia in those who got a Shingrix shot was 23% lower than in people who got a flu shot and 28% lower in people who got a tDAP vaccine, further supporting the idea that there’s something unique about being vaccinated for shingles that’s lowering dementia risk.

“It will be critical to study this apparent effect further,” said Dr. Sheona Scales, director of research at Alzheimer’s Research UK, in written comments.

“While research into whether vaccines affect dementia risk continues, people should be aware that there are other factors that have definitively been linked to an increased dementia risk. These include things like smoking, high blood pressure and excessive alcohol consumption,” Scales added. And controlling those can make a difference in brain health, too.

A second study with similar findings

A second study, which is scheduled to be presented Tuesday at the Alzheimer’s Association International Conference, uses a similar approach as the Oxford study, and its conclusions mirror those findings.

It was sponsored by GSK, which issued a news release describing the results. The full study has not yet been peer-reviewed by outside experts or published in a medical journal.

This research also makes use of another large database of electronic health records, which is owned by the health care company Optum.

By mining the data on nearly 600,000 patients, researchers were able to compare the diagnosis of dementia in people 50 and older who were vaccinated against shingles – with either the older Zostavax vaccine or the newer Shingrix vaccine – against people who were vaccinated with Pneumovax, which protects against bacterial infections that cause strep throat and pneumonia.

After vaccination against shingles, people included in the study were less likely to be diagnosed with dementia than those who got only the Pneumovax vaccine.

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After five years, people who got Zostavax were 8% less likely to be diagnosed with dementia and those who got Shingrix were about 20% less likely to have dementia as a diagnosis in their health records compared with people who got only a Pneumovax vaccine. This finding suggests that protecting against the shingles virus is responsible for the difference, rather than just vaccination alone or the healthy user effect.

This study also found that the new shingles vaccine was associated with a larger degree of benefit than the older one. People who got the Shingrix vaccine were about 23% less likely after five years to have a diagnosis of dementia compared with people who got Zostavax.

Although the findings are intriguing, the association needs more study before researchers can know for sure that the shingles vaccine is definitively behind the benefit.

“The data are at this point an indication for more study, rather than into a signal that we should change how we use the vaccine,” said Dr. Phil Dormitzer, who leads vaccine research and development for GSK.

So for the time being, the best reason to get a shingles vaccine is still to avoid the misery of shingles.

Given the recent findings, researchers are exploring the possibility that shingles vaccines, such as Shingrix, may also contribute to a delayed onset of dementia.
If further studies confirm that shingles vaccines can protect memory and thinking, it could have significant implications for public health, potentially reducing the risk of dementia among vaccinated individuals.