Getting vaccinated against shingles can reduce the risk of developing dementia, a large new study finds.
The results provide some of the strongest evidence yet that some viral infections can have effects on brain function years later and that preventing them can help stave off cognitive decline.
The study, published on Wednesday in the journal Nature, found that people who received the shingles vaccine were 20 percent less likely to develop dementia in the seven years afterward than those who were not vaccinated.
“If you’re reducing the risk of dementia by 20 percent, that’s quite important in a public health context, given that we don’t really have much else at the moment that slows down the onset of dementia,” said Dr. Paul Harrison, a professor of psychiatry at Oxford. Dr. Harrison was not involved in the new study, but has done other research indicating that shingles vaccines lower dementia risk.
Whether the protection can last beyond seven years can only be determined with further research. But with few currently effective treatments or preventions, Dr. Harrison said, shingles vaccines appear to have “some of the strongest potential protective effects against dementia that we know of that are potentially usable in practice.”
Shingles cases stem from the virus that causes childhood chickenpox, varicella-zoster, which typically remains dormant in nerve cells for decades. As people age and their immune systems weaken, the virus can reactivate and cause shingles, with symptoms like burning, tingling, painful blisters and numbness. The nerve pain can become chronic and disabling.
In the United States, about one in three people develop at least one case of shingles, also called herpes zoster, in their lifetime, the Centers for Disease Control and Prevention estimates. About a third of eligible adults have received the vaccine in recent years, according to the C.D.C.
Several previous studies have suggested that shingles vaccinations might reduce dementia risk, but most could not exclude the possibility that people who get vaccinated might have other dementia-protective characteristics, like healthier lifestyles, better diets or more years of education.
The new study ruled out many of those factors.
“It’s pretty strong evidence,” said Dr. Anupam Jena, a health economist and physician at Harvard Medical School, who was not involved in the study but reviewed it for Nature.
The study emerged from an unusual aspect of a shingles vaccine rollout in Wales on Sept. 1, 2013. Welsh officials established a strict age requirement: people who were 79 on that date were eligible for the vaccine for one year, but those 80 and older, were ineligible. As younger people turned 79, they became eligible for the vaccine for one year.
The age cutoff — imposed because of a limited supply and because the vaccine was then considered less effective for people over 80 — set up a “natural experiment,” said Dr. Pascal Geldsetzer, an assistant professor of medicine at Stanford and the study’s senior author.
It allowed scientists to compare relatively equal groups: people eligible for the vaccine with people just slightly older who couldn’t get it. “If I take 1,000 people born one week and 1,000 people born one week later, there shouldn’t be any difference between them, except for the large difference in the vaccination uptake,” Dr. Geldsetzer said.
Researchers tracked health records of about 280,000 people who were age 71 to 88 and without dementia when the rollout began. Over seven years, nearly half of those eligible for the vaccine received it, while only a tiny number from the ineligible group were vaccinated, providing a clear before-and-after distinction.
To limit the likelihood of differences between the groups, researchers used statistical analysis to more heavily weigh data from people just one week on either side of the cutoff: those who turned 80 in the week before rollout and those who turned 80 in the week after.
They also examined medical records for possible differences between the vaccinated and unvaccinated. They evaluated whether unvaccinated people received more diagnoses of dementia simply because they visited doctors more frequently, and whether they took more medications that could increase dementia risk.
“They do a pretty good job at that,” said Dr. Jena, who wrote a commentary about the study for Nature. “They look at almost 200 medications that have been shown to be at least associated with elevated Alzheimer’s risk.”
He said, “They go through a lot of effort to figure out whether or not there might be other things that are timed with that age cutoff, any other medical policy changes, and that doesn’t seem to be it.”
The study involved an older form of shingles vaccine, Zostavax, which contains a modified version of the live virus. It has since been discontinued in the United States and some other countries because its protection against shingles wanes over time. The new vaccine, Shingrix, which contains an inactivated portion of the virus, is more effective and lasting, research shows.
A study last year by Dr. Harrison and colleagues suggested that Shingrix may be more protective against dementia than the older vaccine. Based on another “natural experiment,” the 2017 shift in the United States from Zostavax to Shingrix, it found that over six years, people who had received the new vaccine had fewer dementia diagnoses than those who got the old one. Of the people diagnosed with dementia, those who received the new vaccine had nearly six months more time before developing the condition than people who received the old vaccine.
There are different theories about why shingles vaccines might protect against dementia. One possibility is that by preventing shingles, vaccines reduce the neuroinflammation caused by reactivation of the virus, Dr. Geldsetzer said. “Inflammation is a bad thing for many chronic diseases, including dementia,” he said, so “reducing these reactivations and the accompanying inflammation may have benefits for dementia.”
Both the new study and the Shingrix study provide support for that theory.
Another possibility is that the vaccines rev up the immune system more broadly. The new study offers some evidence for that theory too. It found that women, who have more reactive immune systems and larger antibody responses to vaccination than men, experienced greater protection against dementia than men, Dr. Geldsetzer said. The vaccine also had a bigger protective effect against dementia among people with autoimmune conditions and allergies.
Dr. Maria Nagel, a professor of neurology at University of Colorado School of Medicine, who was not involved in the study, said both theories could be true. “There’s evidence for a direct effect as well as an indirect effect,”, said Dr. Nagel, who has consulted for the manufacturer of Shingrix, GSK.
She said some studies have found that other vaccines, including those against flu, create a generalized neuroprotective effect, but that because the shingles virus hides in nerves, it makes sense that a shingles vaccine would be particularly protective against cognitive impairment.
The study did not distinguish between types of dementia, but other research suggests that “the effect of the shingles vaccine for Alzheimer’s disease is much more pronounced than for another dementia,” said Svetlana Ukraintseva, a biologist at Duke who coauthored a recent study on Alzheimer’s and other dementias and vaccines. She said that might be because some Alzheimer’s cases are associated with compromised immunity.
The Welsh population in the study was mostly white, Dr. Geldsetzer said, but the report also suggested similar protective effects by analyzing death certificates in England for deaths caused by dementia. His team has also replicated the results in Australia, New Zealand and Canada.
Dr. Jena said the connection should be studied further and noted that reducing dementia risk is not the same as preventing all cases. Still, he said, the evidence suggests that “something about the exposure or access to the vaccine has this effect on dementia risk years later.”
