April 2, 2025

expert reaction to study suggesting shingles vaccine (Zostavax) associated with lower risk of dementia

A study published in Nature looks at the effect of the shingles vaccine (Zostvax) on dementia risk. 

Comments provided by our friends at the Australian Science Media Centre:

Dr Joseph Doyle, Professor of Infectious Diseases at Monash University and President of the Australasian Society for Infectious Diseases, said: 

“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.”  

Professor Anthony Hannan, Group Head of the Epigenetics and Neural Plasticity Group at the Florey Institute of Neuroscience and Mental Health, said:

“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 exerts 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.”

Dr Henry Brodaty, Scientia Professor of Ageing and Mental Health and Co-Director of the Centre for Healthy Brain Ageing at the University of New South Wales, said:

“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.”

‘A natural experiment on the effect of herpes zoster vaccination on dementia’ by Markus Eyting et al. was published in Nature at 16:00 UK time on Wednesday 2 April 2025. 

DOI: 10.1038/s41586-025-08800-x

Declared interests

Professor Anthony Hannan: No COI’s.

Dr Henry Brodaty: is or has been an advisory board member or consultant to Biogen, Eisai, Eli Lilly, Medicines Australia, Roche and Skin2Neuron. He has received funding from the National Health and Medical Research Council (NHMRC).

Prof Joseph Doyle: is a board member of the Australian Society for Infectious Diseases and the Pharmaceutical Benefits Advisory Committee. The views expressed here are personal opinions and are not necessarily those of his employers or professional bodies.