People who receive the live-attenuated shingles vaccine may have a lower likelihood of being diagnosed with dementia compared with those who do not get the shot, researchers report April 2 in Nature.
The findings stem from a Welsh vaccination program. The researchers explored how vaccination against shingles — an illness that develops when the virus causing chicken pox reactivates later in life — might influence dementia risk, finding a more prominent effect in women than in men.
Shingles can lead to painful rashes and serious complications. The U.S. Centers for Disease Control and Prevention recommends that adults 50 and older receive two doses of the recombinant shingles vaccine, which includes an antigen that elicits an immune response.
Prior studies suggested a link between shingles vaccination and lower dementia risk, including dementia caused by Alzheimer’s disease. While those studies compared dementia rates between vaccinated and unvaccinated people, such comparisons can introduce bias, the authors of the new study say. For example, people who choose to get vaccinated may be more health-conscious than those who do not, potentially leading to a lower risk of dementia via mechanisms unrelated to the shingles vaccine.
To mitigate this bias, epidemiologist Pascal Geldsetzer of Stanford University and his colleagues focused on a shingles vaccination program in Wales. In 2013, the Welsh government began offering the live-attenuated shingles vaccine — which contains a weakened version of the virus — to people born on or after September 2, 1933.
Comparing individuals born just before and after that date created a natural experiment similar to a randomized controlled trial. “This was a really exciting approach,” says Maria Glymour, an epidemiologist at Boston University who was not involved in the study. “This team identified a situation where people who get the treatment — in this case, the shingles vaccine — were not really different than people who were much less likely to get it.”
The study tracked dementia diagnoses for more than 280,000 individuals born between September 1, 1925, and September 1, 1942. Over at least the roughly three years before and after the eligibility cutoff date, the researchers noted a steady decline in the probability of a dementia diagnosis with later birth dates, with a notable drop once eligibility kicked in.
Among those one week too old to be eligible for the program, 0.01 percent received the vaccine at some point, while about 47 percent of those who were born one week after the eligibility cutoff date did. The probability of being diagnosed with dementia over a seven-year period starting September 1, 2013, was roughly 15.5 percent for people born one week before the eligibility cutoff date and just over 14 percent for people born one week after the eligibility cutoff date. Considering that not everyone in the latter group was vaccinated, the researchers estimate that receiving the vaccine led to a 20 percent relative reduction in dementia risk.
By preventing shingles infections, which have been linked to dementia development, the researchers suggest that vaccination may curb dementia. The team also proposes that the live-attenuated vaccine may affect the immune system in other ways that prevent or delay dementia onset, independent of the shot’s role in preventing the virus’s reactivation.
The researchers did not find a statistically significant difference in dementia rates between groups of men who were or weren’t eligible for the vaccine. The effect was much more prominent in women. The authors suggest that this may be due to, for example, differences in how the immune systems of women respond to the live-attenuated vaccine, an idea that Glymour says seems plausible.
“People should get the shingles vaccine because it prevents shingles,” says Maxime Taquet, a clinical data scientist at the University of Oxford who was not involved in the study. “But if they have the added benefit of preventing dementia, this is excellent news.”
Taquet believes the study’s focus on the live-attenuated vaccine may limit its implications. The live-attenuated vaccine was discontinued in the United States in 2020 in favor of the newer recombinant shot. In a 2024 study, Taquet and his colleagues found that the recombinant shingles vaccine also lowers dementia risk. Not only that, the researchers also claim that it does so better than the live-attenuated shot. So, he says, future studies should focus on the recombinant vaccine.
Geldsetzer agrees that it would be important to investigate the effect of the recombinant shingles vaccine. But, he says, the live-attenuated vaccine remains relevant: It’s still produced in other parts of the world, requires just one shot instead of two and is cheaper to manufacture.