EXPERT REACTION: Shingles vaccine reduces dementia risk by a fifth over seven years

The 2025 Nature study by Geldsetzer et al. presents compelling evidence that the live-attenuated herpes zoster vaccine (Zostavax) may reduce dementia incidence by approximately 20%, derived from a cohort of 282,541 individuals in Wales.

Employing a regression discontinuity design, the study compares dementia outcomes in individuals born just before and after September 2, 1933 (the eligibility cutoff for vaccination starting September 1, 2013). This approach minimises confounding, suggesting a causal association between vaccination and a lower rate of dementia diagnoses over seven years.

The findings align with evidence implicating varicella-zoster virus (VZV) reactivation in neurodegenerative processes, potentially through neuroinflammation. The potential implications are substantial. Should causality be established, this widely available vaccine could serve as a cost-effective tool to mitigate dementia, a global health challenge impacting millions and imposing significant economic burdens.

Notably, the effect was more pronounced in women, hinting at sex-specific immunological or pathological differences that merit further investigation. Currently, these results could bolster vaccination uptake and inform public health strategies. Future research must prioritise randomised controlled trials to confirm causality and elucidate mechanisms, possibly VZV suppression or broader immune modulation.

Evaluating the recombinant zoster vaccine (Shingrix) could extend these insights. The key takeaway is that herpes zoster vaccination might offer dual benefits, protecting against both shingles and dementia. This warrants urgent attention from health authorities to fund rigorous studies and optimise vaccine access, given the profound public health potential of these findings.

They examined the effect of a live virus to prevent shingles administered to people aged 79 to 80. The researchers took advantage of a decision in Wales that 79-80-year-olds born before 2nd September 1933 were ineligible for life to receive the shingles vaccine, whereas those born on or after that day were eligible for at least one year to receive the vaccine. There were 16,595 adults who had become eligible for the vaccine from a total sample of 282,541 adults in the sample.
 
They compared people who were one week too old with those who were one week younger. Those who received the vaccine had an absolute reduction of 7% of developing dementia over the next seven years. Compared to those who were unvaccinated, their risk of dementia was 20% lower. The benefits were stronger for women than men.

The authors examined multiple competing hypotheses to explain the results. There were no differences in dementia diagnoses for those who had and had not received influenza vaccines. Other possible explanations were also discounted. The authors considered the possible mechanism maybe preventing the reactivation of the shingles of the herpes varicella virus. The authors confirmed their findings in a different population by combining a different type of data from England and Wales and using deaths certified as being due to dementia.

Limitations include that these results only pertained to 79-80-year-olds in Wales and to the use of the live vaccine. 

There has been evidence for some time that older people who receive their vaccinations in general are less likely to develop dementia. This is the best evidence yet to show this. Future research will determine whether the newer non-live virus, Shingrix will provide the same benefit and whether immunisation at younger ages may be just as effective.

The paper [by Eyting and colleagues in Nature] presents results of a natural experiment in Wales, United Kingdom, on the effect of shingles vaccination on new diagnosis of dementia. The study observed that older adults appeared to have less chance of dementia diagnosis in the seven years after receiving live-attenuated shingles vaccination (Zostavax). The authors estimate there were 3.5% fewer dementia diagnoses among people who received the live-attenuated shingles vaccine.

This study had an observational design, so we need to be cautious in assuming the vaccine itself caused this decline in dementia diagnoses. It is plausible that episodes of infection, immune system changes, or health care engagement are among the factors behind this association, but further research is needed to help determine whether there is a causal link.

Importantly, we don’t know whether these findings apply to both the live-attenuated shingles vaccine (Zostavax) used in their study and the newer recombinant subunit shingles vaccine (Shingrix) now used widely in Australia. 

Australia approved and subsidised Shingrix on the National Immunization Program in 2023. This newer shingles vaccine is available for older adults and is safer for people who are immunocompromised. 

While we do not know whether the newer shingles vaccine used locally has the same association with less dementia yet, we do know the shingles vaccine provided free in Australia is very effective and protective against episodes of shingles. 

Older adults and people with weak immune systems at higher risk of shingles are encouraged to see their doctor to talk more about vaccination.

The new study from Stanford and the Welsh cohort adds powerful evidence that vaccines may reduce the risk of dementia—by up to 20% over seven years following the shingles vaccine.

This is a landmark finding in brain health and disease prevention. It supports the emerging understanding that infections—especially neurotropic viruses like varicella-zoster—can contribute to long-term neurological decline.

We’ve seen similar mechanisms at play with post-COVID-19 Neurological Syndrome, including persistent brain fog, memory issues, and fatigue. In both conditions, the virus affects the nervous system and may trigger immune and inflammatory responses that harm the brain over time. These findings reinforce one of the most critical messages from our World Brain Day campaigns: prevention matters most.

Vaccination, early intervention, and public education are essential tools to protect the brain across the lifespan. This is not just about treating disease—it’s about reducing risk before damage begins.
Brain health must become a priority at every level of care and policy.

The researchers in Wales conducted a natural experiment based on vaccine eligibility that meant two groups of people were compared in such a way that it was essentially a randomised controlled trial, which is the best way to see if an intervention has an impact.

This study followed up on previous research looking at whether the shingles vaccine could prevent dementia. They used a vaccine not containing live virus. In this natural experiment, the researchers found that use of the shingles vaccine "reduced the probability of a new dementia diagnosis" by about 20% over a 7-year period.

The mechanisms for this aren't clear. One possibility is that getting shingles causes inflammation and forms plaques in the brain that can lead to dementia; therefore, preventing shingles through vaccination reduces those processes. Another possibility is that the vaccine itself causes an immune response independent of its impact on shingles that is beneficial in preventing dementia.

Regarding this latter possibility, we see the opposite with measles, where natural infection with measles can reduce one's immunity to other infections i.e. it has broader impacts beyond its own disease. If the findings of this study are indeed accurate, it will be a potentially simple way to reduce the risk of dementia, which already affects over 50 million people worldwide, and is likely to become a bigger and bigger issue as our life expectancies increase.

This new research article in Nature adds to the evidence that the nervous system and immune system closely interact, and that this has implications for dementia risk, as well as potentially new approaches to dementia prevention and treatment.  Furthermore, it provides evidence that vaccination has the potential to impact positively on human health, beyond the particular disease that the vaccine was intended to prevent.  

A key question, not answered by this new study, is how the shingles (herpes zoster) vaccine may have helped protect (reducing risk by 20%) against dementia. We now know that, despite the blood-brain barrier, the brain has its own immune cells, which serve many roles including removal of specific toxic molecules that accumulate with age (particularly in the most common form of dementia, Alzheimer’s disease).  

It is possible that the vaccine had direct effects on these brain immune cells, but it is also possible that the vaccine acted indirectly, for example by slowing brain aging and/or enhancing brain resilience to the ravages of age. The next step is to work out exactly how this vaccine exerted its protective effects against dementia, and to use that information to develop new ways to prevent and treat dementia. It also increases the likelihood that in future there may be specific vaccination programs whose primary aim is to prevent dementia.