“The shingles vaccines … seem to be one of those drugs,” said Taquet, who was not involved in the study.
A “natural experiment”
In medical research, randomised controlled trials are the gold standard for measuring the effectiveness of a treatment or intervention by randomly dividing similar participants into treatment and control groups.
However, this controlled comparison is often not possible in the real world. For example, people who get vaccinated tend to also have other health behaviours different from those who don’t, which makes these two groups difficult to compare.
The new study took advantage of a historical quirk in how Wales rolled out its shingles vaccination programme in September 2013. Only Welsh adults who were born on or after September 2, 1933, were eligible for the shingles vaccine; those born before that date were ineligible.
This public health policy essentially set up a “natural experiment” of comparing two groups of people with nearly identical backgrounds and ages who either met the vaccine eligibility cutoff or missed it, researchers said.
“I think it’s as close as we can get to doing a randomized clinical trial without actually doing one,” said Pascal Geldsetzer, an assistant professor of medicine at Stanford University School of Medicine and senior author of the study.
When Geldsetzer and his colleagues analysed the electronic health records, they found that over a seven-year follow-up period, people who received the shingles vaccine had a 3.5% reduced probability of being diagnosed with dementia. This was equivalent to a 20% reduction in relative dementia risk from vaccination.
To account for possible confounding variables that could explain this drop in dementia risk, the researchers conducted extensive analyses for factors such as differences in health behaviours or health-care usage but found no other plausible explanation.
The results of the study – which looked at the effect of Zostavax, a first-generation vaccine made from live, weakened zoster virus – line up with previous research.
A 2024 study conducted by Taquet and his colleagues compared the health records of Americans who received the Zostavax shingles vaccine with those who received the Shingrix shingles vaccine when Zostavax was put into disuse in the United States in 2017 because of waning efficacy in protecting against shingles. (Zostavax was discontinued in 2020.)
They found that Shingrix is more effective at preventing shingles and was associated with a significant reduction in dementia risk and 17% more time before a diagnosis.
“I think these two studies together, done in different populations, in different countries, both point to the same conclusion,” Taquet said. “It’s the convergence of evidence which is very nice to see.”
Shingles vaccine and dementia link
There are two main potential biological mechanisms that link the shingles vaccine with reduced dementia risk, researchers said.
First, the shingles vaccines reduce the risk of reactivations of the varicella-zoster virus which causes chickenpox in childhood and remains dormant in nerve cells afterward. The virus can get reactivated in adulthood and manifest as shingles, which is characterised by a burning, painful rash.
Reactivations of the varicella-zoster virus are associated with increased dementia risk, potentially because of the resulting inflammation, which is increasingly being recognised as important for the development of dementia, Geldsetzer said.
(Other research has found correlations between other types of infections and increased dementia risk; associational studies have also reported different vaccines can reduce dementia risk.)
Second, the vaccine itself may have a broader effect in activating the immune system, which may be beneficial to delaying or preventing dementia, researchers said.
These two mechanisms are not mutually exclusive, and both may play a role, Taquet said.
Interestingly, both studies also found that the vaccine’s protective effect was stronger in women than men, though the reason is not yet clear. Women may have a different, stronger response to vaccines and in how dementia develops; women are twice as likely to develop Alzheimer’s disease as men.
Geldsetzer believes that a randomised controlled trial on the effect of the Zostavax shingles vaccine on dementia and cognition is needed to “convince the public health and medical community”. He wants to test the vaccine made from a live attenuated virus to build on the evidence from his natural experiment studies.
How to reduce dementia risk
A shingles vaccine is “a one-off intervention that’s really very inexpensive and that is readily available” that may have larger effects than current dementia therapeutics, Geldsetzer said.
In addition, 45% of dementia cases could be delayed or prevented with lifestyle and environmental changes, according to the 2024 Lancet Commission report on dementia.
To cut dementia risk and lengthen our cognitive health spans, studies suggest steps such as staying socially connected, moderating alcohol intake, maintaining a healthy blood pressure and addressing hearing loss (such as with hearing aids).
