Shingles Vaccine Gains New Role in Fight Against Dementia

Researchers have found that the shingles vaccine may help reduce the risk of developing dementia. Using health data from thousands of people in Wales, they found that those who received the vaccine had fewer cases of dementia over the years. This effect appears to be related to the way the vaccine activates the immune system, going beyond protecting against the virus.

Recently, scientists have been finding increasing evidence that certain viruses, such as herpesviruses (the same ones that cause herpes), may be linked to the development of dementia. One idea to combat this risk is to use vaccines against these viruses.

In addition, research shows that some vaccines, especially those made with weakened live viruses, may have benefits that go beyond protecting against the specific disease for which they were created. These extra effects, called “off-target effects”, can vary between men and women.

The shingles vaccine, also known as the shingles vaccine, was developed to protect against the varicella-zoster virus, which causes chickenpox and can reactivate years later as shingles. There are two main versions: the live attenuated vaccine (Zostavax) and the newer, more effective recombinant vaccine (Shingrix).

Vaccination is especially recommended for older adults, as the risk of developing shingles and its complications, such as chronic pain, increases with age.

To date, most studies that have tried to understand whether vaccines help prevent dementia have compared vaccinated people with unvaccinated people. But this is tricky, because people who get vaccinated are often different, and may be more careful about their health, for example, which could bias the results.

To overcome this problem, a new study in Wales used a different strategy. From September 2013, anyone born after September 2, 1933, was eligible for the shingles vaccine (known as Zostavax), while anyone born before that was not.

Because the age difference between these groups is only a few days or weeks, they are very similar in every way except the chance of having been vaccinated, acting as a “natural experiment.”

The researchers analyzed health records of thousands of people and confirmed that those born shortly after the date were much more likely to receive the vaccine. More importantly, they found that over the course of seven years, vaccinated people had about a 20 percent lower risk of being diagnosed with dementia compared to unvaccinated people.

The protective effect was even stronger among women. In addition, the vaccine did not alter the risk of other diseases, nor did it encourage more people to seek other types of vaccination or medical care, supporting the idea that the effect was indeed due to the shingles vaccine.

The researchers also ran additional tests to ensure that no other factors influenced the results and were able to replicate the findings in other databases. As a result, this study provides some of the strongest evidence yet that shingles vaccination can help prevent or delay the onset of dementia.

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A natural experiment on the effect of herpes zoster vaccination on dementia

Markus Eyting, Min Xie, Felix Michalik, Simon Heß, Seunghun Chung and Pascal Geldsetzer, 

Nature. 2 April 2025

DOI: 10.1038/s41586-025-08800-x

Abstract:

Neurotropic herpesviruses may be implicated in the development of dementia1,2,3,4,5. Moreover, vaccines may have important off-target immunological effects6,7,8,9. Here we aim to determine the effect of live-attenuated herpes zoster vaccination on the occurrence of dementia diagnoses. To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual’s exact date of birth. Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least 1 year to receive the vaccine. Using large-scale electronic health record data, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely 1 week too old to be eligible, to 47.2% among those who were just 1 week younger. Apart from this large difference in the probability of ever receiving the zoster vaccine, individuals born just 1 week before 2 September 1933 are unlikely to differ systematically from those born 1 week later. Using these comparison groups in a regression discontinuity design, we show that receiving the zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of 7 years by 3.5 percentage points (95% confidence interval (CI) = 0.6–7.1, P = 0.019), corresponding to a 20.0% (95% CI = 6.5–33.4) relative reduction. This protective effect was stronger among women than men. We successfully confirm our findings in a different population (England and Wales’s combined population), with a different type of data (death certificates) and using an outcome (deaths with dementia as primary cause) that is closely related to dementia, but less reliant on a timely diagnosis of dementia by the healthcare system10. Through the use of a unique natural experiment, this study provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence.