Summary: A large population study found that older adults who received the shingles vaccine were substantially less likely to be diagnosed with dementia over the next seven years. The research took advantage of a rare, age-based vaccine rollout in Wales that closely resembles a randomized trial, enabling investigators to estimate the vaccine’s effect more reliably than prior studies.
Beyond preventing new cases, the vaccine was also associated with slower disease progression and lower dementia-related death rates among people already living with dementia. These results add to growing evidence that viral reactivation in the nervous system may play a meaningful role in neurodegenerative disease.
Key Facts
- Dementia risk reduction: Vaccinated older adults had about a 20% lower risk of being diagnosed with dementia over seven years.
- Possible therapeutic benefit: People with existing dementia who received the vaccine were less likely to die from dementia during follow-up.
- Biological implication: Findings support the idea that reactivation of latent viruses such as varicella-zoster may contribute to dementia risk.
Source: Stanford
An unusual public health policy in Wales created a valuable natural experiment suggesting a shingles vaccine can reduce dementia risk.
In a study led by Stanford Medicine, researchers examined health records from Wales and found that older adults who received the shingles (herpes zoster) vaccine were about 20% less likely to develop dementia in the following seven years than comparable people who did not receive the vaccine.
The results, reported April 2 in Nature, strengthen a theory that infections affecting the nervous system can raise the risk of dementia. A follow-up study to appear Dec. 2 in Cell indicates the vaccine may also slow cognitive decline for people already diagnosed with dementia.
Lifelong infection and dementia
Shingles is caused by reactivation of the varicella-zoster virus, the same virus that causes chickenpox. After the initial infection, usually in childhood, the virus can remain dormant in nerve cells for life and reactivate later, most commonly in older adults or people with weakened immune systems.
Dementia affects tens of millions worldwide, and prevention strategies remain limited. Historically, research has focused on brain plaques and tangles associated with Alzheimer’s, but a lack of breakthroughs has prompted exploration of other contributors, including chronic or reactivating viral infections.
Previous observational studies suggested a link between shingles vaccination and lower dementia rates, but they were vulnerable to bias: individuals who choose vaccination often differ from those who do not in health behaviors and lifestyle factors not captured in routine health records.
“People who get vaccinated typically differ in many unmeasured ways from those who don’t,” said Pascal Geldsetzer, MD, PhD, assistant professor of medicine and senior author of the new study. “That makes it hard to draw causal conclusions from ordinary observational data.”
A natural experiment in Wales
The Wales vaccination program provided an unusual opportunity to reduce this bias. Starting Sept. 1, 2013, the program made the live-attenuated shingles vaccine available to anyone who was 79 on that date for one year. Those who were 78 would be eligible the following year; people who were already 80 or older on Sept. 1, 2013, were never eligible under that policy.
This narrow, date-driven eligibility rule meant that people who turned 80 just before the program start were ineligible for the vaccine, while those who turned 80 just after were eligible, creating groups that are essentially identical except for that small age difference. Comparing these groups allowed researchers to estimate the causal effect of vaccine eligibility and, by accounting for actual uptake, of receiving the vaccine itself.
The team analyzed health records for more than 280,000 adults aged 71 to 88 who were free of dementia at the start of the program, focusing on individuals born in the weeks immediately before and after the eligibility cutoff. “If you take people born a week apart, they should be similar in most respects,” Geldsetzer said. “Only the eligibility rule differs.”
Protection observed
Over seven years, vaccination cut the incidence of shingles by roughly 37% among those who received the live-attenuated vaccine, consistent with prior clinical trial evidence. More importantly for dementia outcomes, vaccinated people were approximately 20% less likely to receive a dementia diagnosis by 2020.
The researchers searched extensively for other explanations but found no meaningful differences between eligible and ineligible groups in education, rates of other vaccinations, or prevalence of conditions like diabetes, heart disease, or cancer. The lone notable divergence was a lower rate of dementia diagnoses among those who received the shingles vaccine.
Geldsetzer noted that the result held up under multiple sensitivity checks, alternate age windows, and outcome definitions, including analyses focused on dementia-attributed deaths. “The protective signal was strong and persistent,” he said.
Benefits across the disease course
Using the same natural experiment, the team also found reduced diagnoses of mild cognitive impairment—often a precursor to dementia—during nine years of follow-up among vaccinated individuals. Strikingly, among the 7,049 Welsh seniors who already had dementia when the vaccination program began, those who received the vaccine were significantly less likely to have dementia listed as the cause of death over the follow-up period: roughly 30% of vaccinated people with dementia died of dementia-related causes versus nearly half of those unvaccinated.
These findings suggest the vaccine could have both preventive and disease-modifying effects.
Sex differences and unanswered questions
The protective association was stronger in women than men. This may reflect biological sex differences in immune response—women often mount higher antibody responses to vaccines—or differences in shingles incidence and dementia pathways. Exactly how vaccination reduces dementia risk remains unknown: it could stem from preventing viral reactivation in the nervous system, enhancing broader immune protection, or another mechanism.
It is also unclear whether the newer recombinant shingles vaccine, which contains viral proteins and provides greater protection against shingles, would have the same or larger effect on dementia risk.
Geldsetzer and colleagues have replicated the Wales findings in datasets from other countries with similar rollout patterns, including England, Australia, New Zealand, and Canada, and are advocating for a large randomized controlled trial to test causality definitively. “We have a one-time, well-tolerated intervention,” he said, and a pragmatic trial could determine whether vaccination directly reduces dementia risk and slows progression.
Funding: The study received funding from The Phil & Penny Knight Initiative for Brain Resilience, the Stanford Center for Digital Health, the National Institute on Aging (grant R01AG084535), the National Institute of Allergy and Infectious Diseases (grant DP2AI171011), and the Biohub, San Francisco.
Key Questions Answered:
A: The study found that older adults who received the shingles vaccine were about 20% less likely to develop dementia over seven years compared with those who did not.
A: The data suggest vaccination may slow progression and reduce dementia-related deaths among people already diagnosed.
A: Researchers hypothesize that preventing reactivation of latent viruses like varicella-zoster or modulating immune responses may reduce harmful effects on the nervous system that contribute to cognitive decline.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by staff.
About this neuropharmacology and dementia research news
Author: Nina Bai
Source: Stanford
Contact: Nina Bai – Stanford
Image: The image is credited to Neuroscience News
Original Research: “The effect of shingles vaccination at different stages of the dementia disease course” by Pascal Geldsetzer et al., Cell. Open access.
Abstract
The effect of shingles vaccination at different stages of the dementia disease course
Using natural experiments, previous work indicated that live-attenuated herpes zoster (HZ) vaccination appeared to prevent or delay dementia diagnoses in Wales and Australia. Here, the authors report that HZ vaccination also reduces diagnoses of mild cognitive impairment and, among patients living with dementia, deaths attributed to dementia. Exploratory analyses suggest the effects are not restricted to a single dementia subtype.
The analysis exploits the fact that people who turned eighty just after the start of the HZ vaccination program in Wales were eligible for the vaccine for one year, whereas those who turned eighty just before were not and remained ineligible. The key strength of these natural experiments is that these comparison groups should be similar on all characteristics except for a tiny age difference. The findings indicate that live-attenuated HZ vaccination can prevent or delay mild cognitive impairment and dementia and may slow disease progression among those already affected.