Both versions of the vaccine – one with a version of the live virus and one without – reduce those reactivations and the risk of dementia, the study found.

Researchers reviewed the electronic medical records of more than 100 million people in the United States from 2007 to 2023. After controlling for 400 different variables – including chronic illnesses, demographics, prescriptions and doctors’ visits – they found a 27–33% lower risk of developing dementia over three years after getting vaccinated.

Those who experienced multiple episodes of shingles had a 7–9% higher risk of dementia three to nine years after the second outbreak, the study found, compared with those who had a single reaction.

More shingles episodes = more dementia risk

Dementia is influenced by a host of complex factors, including genetics, environment and viral infections. And while the number of Americans who develop the disease each year is rising, there are few effective treatments and no ways to prevent it outside of lifestyle changes.

Despite promising research, the biology behind how varicella–zoster affects dementia remains unclear.

There are theories. One, researchers say, is that the varicella–zoster virus, which is “continuously” reactivating even when it’s not causing observable symptoms, directly affects parts of the brain implicated in dementia.

Another has to do with the body’s natural immune response to infections – inflammation – and whether there’s a toxic effect on the brain if the virus reactivates. “So, it’s not necessarily that the virus itself is directly attacking cells of the brain, but the inflammatory response to the presence of that virus is what causes problems,” said Anupam Jena, an internist at Massachusetts General Hospital.

Or, could it be the medications used to treat the painful, debilitating symptoms? “We don’t know,” Jena said.

The study’s findings suggest, however, that those who received multiple doses of the shingles vaccine were better protected from dementia, bolstering previous research showing that having two doses rather than one of the Shingrix vaccine reduces reactivations of the varicella–zoster virus.

Better understanding whether varicella–zoster virus helps drive neurodegeneration is a step toward finding better ways to treat dementia, said Patrick Schwab, the study’s lead author and senior director of machine learning and artificial intelligence at GSK, a biopharmaceutical company that manufactures one of the shingles vaccines.

The study found that people who received two doses of Shingrix, a newer vaccine containing inactivate portions of the virus and manufactured by GSK, had an 18% lower dementia risk five years post vaccination compared with those who received a single dose of Zostavax, an older vaccine made from live, weakened zoster virus. (Zostavax was removed from the US market in 2020.)

It also found that women over 50 who received Zostavax had a 35% lower risk of dementia three years after getting the shot. Women between 80 and 89 who received two doses of Shingrix saw a 39% lower risk three years after vaccination.

“The results were really remarkable in their consistency,” said Schwab, who is also head of the biomedical AI group at GSK. “And this is what ultimately made the study so exciting.”

One “tricky bit about the study”, Schwab said, is that it could only measure occurrences of varicella–zoster that appeared in clinical records as a shingles diagnosis, meaning it became “a proxy for reactivation in general”.

What it means for patients

Shingles vaccines are already recommended for older people and people with weakened immune systems. Some clinicians said evidence is now strong enough that they would discuss dementia prevention with patients as an added benefit. Jena, the Joseph P. Newhouse Professor of Health Care Policy at Harvard Medical School, said he recently raised the research while teaching a group of medical residents who hadn’t even heard of the connection.

Jena peer–reviewed an earlier study co–written by Geldsetzer that followed more than 280,000 adults in Wales and found that people who got the shingles vaccine had a 20% lower risk of developing dementia over seven years.

He said the latest study does several things that boost the robustness of their findings and provide “pretty good quality evidence”. For example, in testing the efficacy of both vaccines for preventing dementia, researchers found that benefits to the brain weren’t permanent and seemed to track with the waning protection of the vaccines.

A.M. Barrett, chair and professor of neurology at UMass Chan Medical School, said the current toolbox to reduce dementia risk is limited and not as effective.

Barrett, a neurologist who is also chief of neurology services at the VA Central Western Massachusetts Healthcare System, worries the issue might become politicised, swept up in growing mistrust of medicine and increasing vaccine hesitancy. “Unfortunately,” she said, “if people are not touched personally by dementia … they might view this as a way of people trying to convince them to take vaccines that are unnecessary.”

But she said vaccination is a relatively inexpensive, widely available intervention.

“You want to have five more years of playing with your grandchildren and five more years of driving really well,” she said. “That’s priceless.”