A shingles shot may do more than prevent rash — it could help shield the aging brain from dementia, according to a landmark study using real-world data from the UK.
Study: A natural experiment on the effect of herpes zoster vaccination on dementia. Image Credit: Kitsawet Saethao / Shutterstock
A routine vaccine could offer more than protection from varicella-zoster virus — it could help delay or prevent dementia, according to a robust natural experiment conducted by Stanford researchers and published in the journal Nature. In a recent study, a research team at Stanford University reported that the herpes zoster (shingles) vaccine may lower the risk of developing dementia, offering a potential new tool in the fight against cognitive decline.
Link between herpesviruses and dementia
For years, scientists have explored potential links between neurotropic herpesviruses and dementia. Some evidence suggests that infections caused by these viruses may contribute to neurodegeneration. While vaccination is commonly used to prevent infections, emerging research indicates that vaccines, especially live-attenuated ones, can have broader effects on the immune system, sometimes influencing conditions unrelated to the targeted disease.
However, previous studies examining the relationship between vaccines and dementia have struggled with a key challenge — distinguishing correlation from causation. Many have simply compared dementia rates between vaccinated and unvaccinated individuals, but this approach is prone to bias. Furthermore, factors such as personal health awareness, access to healthcare, and even cognitive ability can influence whether someone gets vaccinated, making it difficult to isolate the true effect of the vaccine.
About the study
In the present study, the researchers utilized the vaccine eligibility rules in Wales, United Kingdom (U.K.), to evaluate the impact of the herpes zoster vaccine on dementia risk. In the U.K., the eligibility for the herpes zoster vaccine was determined solely by birth date. Those born on or after September 2, 1933, were eligible to receive the vaccine, while those born just before this date were not.
This provided the researchers with a unique opportunity to study the vaccine’s effect on dementia risk, as individuals born just a few weeks apart are unlikely to differ in any meaningful way in other aspects of life, except for their access to the vaccine. This rare policy feature enabled researchers to apply a regression discontinuity design, simulating a natural experiment that is highly resistant to confounding. The authors also confirmed their findings using a difference-in-differences instrumental variable (DID-IV) approach, further reinforcing the robustness of their causal claims.
By analyzing large-scale electronic health records, the researchers could compare the long-term dementia risk between these two groups while minimizing confounding factors. The findings were corroborated in a secondary analysis of dementia-related deaths across England and Wales, further strengthening the causal inference. The study used regression discontinuity design, a statistical technique for determining causal relationships, and analyzed data from a seven-year follow-up period.
Major findings
The study found that receiving the herpes zoster vaccine was associated with a 3.5 percentage point reduction in dementia diagnoses over seven years, which translates to a 20% relative decrease. This estimate accounts for the fact that not all individuals who were eligible actually received the vaccine. The protective effect was stronger in women, reaching statistical significance, while the findings in men were inconclusive due to wider confidence intervals.
To confirm their findings, the researchers conducted a separate analysis using death certificate data. This secondary analysis supported their initial conclusions, showing that eligibility for the herpes zoster vaccine reduced dementia-related deaths by approximately 5% over nine years.
Beyond dementia, the study also confirmed that the vaccine significantly reduced the occurrence of shingles, consistent with clinical trial data. However, the observed reduction in dementia risk could not be fully explained by a decrease in shingles cases alone, suggesting that other mechanisms might be at play. Notably, the reduction in dementia incidence only became evident more than one year post-vaccination, supporting theories of long-term immune modulation.
The researchers explored several potential explanations for the vaccine’s apparent protective effect. One hypothesis was that the vaccine helps suppress reactivations of the varicella-zoster virus, which causes shingles. Some studies have suggested that such viral reactivations may contribute to neuroinflammation, a key factor in dementia development.
Another potential mechanism suggested a broader immune-modulating effect of the vaccine. Live-attenuated vaccines, like the herpes zoster vaccine, can stimulate the immune system in ways that extend beyond their primary target. This immune boost may help the body combat other infections or neuroinflammatory processes linked to dementia, potentially via mechanisms such as trained immunity or heterologous adaptive immunity. The study also explored how prior influenza vaccination and autoimmune conditions may modify the vaccine’s effect, supporting the hypothesis that broader immune modulation could contribute to dementia protection.
While these findings are compelling, the researchers acknowledged several limitations. One challenge was the potential under-detection of dementia in health records, as not all cases are formally diagnosed. The study also focused on a specific age group, making it difficult to apply the results to younger populations.
Another important consideration was that the study examined only the live-attenuated herpes zoster vaccine. Importantly, the study focused on the live-attenuated vaccine Zostavax, as the recombinant vaccine Shingrix was introduced only after the study period ended. It is unclear whether the newer vaccine would have the same effects on dementia risk.
Implications and conclusions
Dementia remains one of the most pressing public health challenges worldwide, with no cure currently available. If further research confirms that vaccines can reduce the risk of dementia, this could open up new avenues for prevention. If validated in other settings, the shingles vaccine could represent one of the most effective and cost-effective preventive strategies for dementia. Furthermore, given the widespread availability and safety profile of the herpes zoster vaccine, these findings suggest a promising, low-risk intervention that could potentially help millions of people.
While further research is needed to understand the exact mechanisms at play, this study provides compelling evidence that the herpes zoster vaccine may do more than just prevent shingles — it may also help protect the aging brain.