Can the shingles vaccine stave off dementia?

[AUDIO LOGO] FLORA LICHTMAN: Hey, it’s Flora Lichtman, and you’re listening to Science Friday. The benefits of getting a vaccine seem relatively straightforward. You get the shingles vaccine, it protects you from shingles. But there may be more to the story.

For example, researchers have found a surprising link between getting the shingles vaccine and a lower risk of developing dementia. And that’s not the only vaccine that seems to boost health in unexpected ways. So what’s going on here?

Here to get into the details are my guests Dr. Pascal Geldsetzer is an epidemiologist at Stanford University who’s studying the association between the shingles vaccine and lower rates of dementia. And Dr. Helen Chu is a physician and epidemiologist at the University of Washington who studies flu, RSV, and COVID-19. Helen, Pascal, welcome to Science Friday.

PASCAL GELDSETZER: Thank you so much for having me.

HELEN CHU: Yeah, thanks for having us.

FLORA LICHTMAN: Thanks for being here. Helen, start by orienting us. Give me some examples of some of the unintended benefits of vaccines beyond preventing the specific disease they were designed for.

HELEN CHU: We think of vaccines as preventing the disease that we’re vaccinating against, flu or RSV or COVID, but oftentimes these vaccines can have other effects like preventing heart attacks or strokes. There are a couple of reasons why we think this happens.

The first is perhaps we are not measuring the infections when they occur. So very well may be that somebody comes in with a heart attack, and the trigger for that heart attack was a flu infection. But we never captured that flu infection. And so when we look at this on a population level in studies, what we can see is that flu vaccines actually prevent heart attacks.

FLORA LICHTMAN: Can I just dig in here for a second? So the idea is that flu could actually trigger a heart attack or a heart health problem. And so if you’re preventing the flu, you’re preventing this downstream effect of having that infection.

HELEN CHU: That’s correct. It could be preventing that. And it’s possible that the flu infection is triggering inflammation in your blood vessels, and that inflammation is what’s causing the heart attack or the stroke. We think that’s what’s happening, and we’re not able to measure that in the way we normally do these studies.

FLORA LICHTMAN: So that’s one potential reason you see these downstream effects. Is there another?

HELEN CHU: I think the main point is that either we’re not measuring it or these things are happening well after the infection is being diagnosed. And so it could be that you could have a heart attack at the time of your hospitalization for flu, but we never captured that flu infection. The other way that it could happen is that that heart attack or stroke happened a few weeks to months later. And we’re not capturing it because it wasn’t at the time of the immediate infection, but that infection triggered this cascade of inflammation that later on led to all of these other adverse events like strokes or heart attacks.

FLORA LICHTMAN: Gotcha. I want to dig into a case study for a couple minutes, and then we’ll zoom back out. But, Pascal, let’s talk about this relationship between the shingles vaccine and dementia. You looked into this. Why did you start investigating this in the first place?

PASCAL GELDSETZER: Well, I think the shingles vaccination program as it was rolled out in several countries provides this really unique opportunity in observational data to get at cause and effect rather than just correlation. We usually always have this fundamental problem in cohort studies, in electronic health record data, medical claims data that we have to compare people who are very different, people who go get vaccinated versus those who don’t, people who are prescribed a certain medication versus those who don’t. And we know that different health behaviors, preventive motivations that drive these decisions, and we just have very– it’s very hard to measure these concepts in the first place. And the measures that we have of these things in electronic health record data are even poorer.

And so we try to adjust for these differences in our statistical analysis, but we never whether we get there. And so we’re always left with the question is this correlation or actual causation.

FLORA LICHTMAN: So that’s the problem with so what I’m hearing is that’s the big problem–

PASCAL GELDSETZER: Yeah.

FLORA LICHTMAN: With these studies about vaccines boosting health outside of what they’re supposed to do is the data is messy and it’s not clear if it’s just a correlation because people who get vaccines tend to be healthier generally.

PASCAL GELDSETZER: Correct, yes. Yeah. yeah, absolutely. And then they have a lower risk of dementia in the future regardless of whether they get the vaccine or not. But in the way the shingles vaccine was rolled out in a number of countries, we’ve got all of a sudden very different comparison groups, in fact, comparison groups that are very similar to what we would have in a clinical trial, which is the gold standard to get at cause and effect.

So they said in a number of countries. So, for example, in the UK, if you had your 80th birthday just prior to the start date of the shingles vaccination program, you were ineligible, and you remained ineligible for life. Well, if you had it just after you were eligible and so now we can compare in our data people whose only difference is a week or so in age, but they have this massive difference in ever getting the vaccine because of this eligibility rule at a pretty arbitrary date of birth eligibility cutoff.

And now you’ve got comparison groups just like in a clinical trial where we know that all that’s different about the control group and intervention group is whether the coin landed on heads or tails. Here, all that’s different about the intervention and the control group is whether you happen to be born just a few days earlier or a few days later essentially by random chance.

So this is what makes this evidence that we’re able to generate for shingles vaccination and its health outcomes so much more powerful and so unique, and such a unique opportunity and observational data to get a cause and effect is really rare. And that’s why I’m so excited about this shingles vaccination program and research and especially these large effects that we keep seeing for dementia.

FLORA LICHTMAN: Yeah, so what did you find?

PASCAL GELDSETZER: Yeah, so we see these large protective effects for new diagnoses of dementia in the future, and we keep seeing this in various different– in all these different settings that have rolled out the shingles vaccine using these date of birth cutoffs. So it’s not a fluke finding. It’s something that repeats in data set after data set. And there are large protective effects which would be–

FLORA LICHTMAN: How large?

PASCAL GELDSETZER: So our best guess is a 20% reduction in new dementia diagnoses over seven years. So that is large, especially given that it’s such a simple, inexpensive, readily available, one-off intervention. It’s not even a medication that you have to take every day, let alone a lifestyle regimen that you have to adhere to over decades. And it’s safe and prevents shingles as well, which is nice. And so you’ve got these a readily scalable intervention with large protective effects, so that would be a big, big deal for population health.

FLORA LICHTMAN: Absolutely. Helen, what do you make of this– these findings?

HELEN CHU: I think this is all very interesting and really exciting to see this in these– they’re called ecologic studies where you look at the before and after and compare these groups. I think that we do need to see some more data to help us understand whether or not these results hold. There are studies that are starting in Denmark. These are larger clinical trials that will evaluate the effect of shingles vaccine on prevention of dementia, and I think those will help answer the question.

It is biologically plausible the idea that–

FLORA LICHTMAN: Say more about that, Helen. Yeah.

HELEN CHU: So we know that these viruses are inflammatory. What they do is they have a predilection for blood vessels, and they cause inflammation. And we know a lot of dementia is what’s called vascular dementia so dementia that results from potentially inflammation of the blood vessels that go to your brain.

And so the idea that you could have a vaccine that prevents inflammation in your vessels that then goes on to prevent heart attacks, strokes, dementia, other long-term outcomes, that is certainly something that could be true. But I think these are early studies and there have been a lot of them, but I think it would be nice to see this in a clinical trial setting to prove that this is the case. But I agree, this is very exciting.

FLORA LICHTMAN: Pascal, I suspect you agree.

PASCAL GELDSETZER: I agree that a clinical trial would be ideal to conclusively test this link. I do think there’s another important potential mechanism here as well, which is that we increasingly realizing that vaccines appear to have broader effects on the immune system beyond the specific antibody response that they have been designed to elicit and that this may not just provide protection against some other pathogens but also potentially against some chronic diseases. And we know that these effects vary strongly by vaccine type and often particularly strong for live attenuated vaccines.

So in our natural experiments using these date-of-birth cutoffs, we have always been studying the live attenuated shingles vaccine. And so I think it’s really important that a clinical trial is done on this vaccine. That’s a vaccine we’ve got the strongest evidence for. It’s an off-patent vaccine essentially. It’s a little commercial interest. So that’s my dream at the moment I’m trying to generate funds from philanthropy, private foundations to run a clinical trial of this vaccine for dementia effects.

FLORA LICHTMAN: If you’re listening, people with money.

PASCAL GELDSETZER: Yes.

[LAUGHTER]

[MUSIC PLAYING]

FLORA LICHTMAN: We have to take a break but when we come back, unintended benefits of other vaccines, what we know, and what we still have to learn. Stay with us.

[AUDIO LOGO]

I want to spend another minute on shingles. Pascal, is there something about the shingles virus that would link it to dementia in particular?

PASCAL GELDSETZER: Yeah, so I think there’s a particularly high level of biological plausibility for the virus that causes shingles later in life, which is the chicken pox virus. Because it is what’s called a neurotropic virus, so it’s preferentially targets your nervous system. We also that these reactivations of the virus as it remains hibernated in your nervous system for life, it’s in this constant interplay with the immune system causes these reactivations. And they cause some sort of inflammatory process in the nervous system including effects on blood vessels that Helen has mentioned. So that these inflammatory processes, essentially we know chronic inflammation is a bad thing for many chronic diseases, and so it’s not far fetched to think that this may have consequences for dementia disease development.

FLORA LICHTMAN: You mentioned this briefly, but, Helen, does it matter if what type of vaccine if it’s mRNA or attenuated live virus, does that change the type of benefits we see?

HELEN CHU: I think there are many ways to think about that. There’s– the live attenuated vaccines have this ability to protect beyond the pathogen. So we see that with measles vaccine. We see that with BCG, which is a vaccine that babies get at birth to prevent against severe tuberculosis disease in certain countries. We know that these types of live vaccines seem to have a broadly protective effect. However–

FLORA LICHTMAN: What does that mean? What do you mean a broadly protective effect?

HELEN CHU: So the way that we think of these live vaccines as working, the tuberculosis vaccine and the MMR vaccine, the measles vaccine, is that they seem to be broadly protective by triggering something called an innate immune response, which is where your body mounts a more non-specific protective response that protects you from diseases beyond just measles or tuberculosis. So babies who get BCG vaccine at birth seem to have protection against other things, not just against tuberculosis.

We think that measles infection depletes your immune system, and the way that it depletes it is that it wipes out all your B cells, the cells that make your antibodies, and prevents you from being able to respond to new infections that you get after your measles infection. So measles infection makes you sick not just from measles but from other things. And so measles vaccine therefore protects you against all of these other things as well.

FLORA LICHTMAN: That’s fascinating.

HELEN CHU: So that’s one way where a live vaccine may be more broadly protective than a killed vaccine or an mRNA vaccine. But we also that the infections themselves, the infections that you’re preventing with either your live vaccine or your mRNA vaccine or any other type of vaccine, those infections themselves are also inflammatory, and so when you protect against that infection, irrespective of which type of vaccine you get, you are preventing the downstream chronic inflammation and these other diseases that are developing.

FLORA LICHTMAN: I mean, Helen, we’ve been talking about viruses that can have a long tail or be re-activated in the body. Do we anything more about COVID vaccines and their protection against long COVID?

HELEN CHU: Yeah, there’s a lot of good data now showing that COVID vaccines are protective against long COVID. And I think that’s really an important message for people to understand is that you may not be at risk for severe disease due to COVID either because you’re younger and you don’t have chronic conditions or because you’ve now received a vaccine multiple times or have had vaccines plus infections. But people are still at risk for developing pretty debilitating symptoms of long COVID, and there have now been multiple studies that have shown that being up to date on your COVID vaccine is protective against development of long COVID.

FLORA LICHTMAN: Does this research into vaccines change our understanding of heart disease or dementia or broaden our understanding of those conditions?

HELEN CHU: I’m an infectious disease doctor, so I think infections cause a lot of things. And I think we’re starting to be proved right and that getting vaccines that prevent these infections really are protective not just for that infection but also may have all of these other downstream effects that we’re really only beginning to understand now.

PASCAL GELDSETZER: Yeah, I totally agree. And I think it’s both the role of pathogens, of infections in chronic diseases, but potentially also the role of the immune system and immune aging and trying to counteract immune aging later in life through vaccination. If we understand these mechanisms better, I think it could lead to so many insights, so many new tools in the future for prevention and treatment. I think it’s a really important area of research.

FLORA LICHTMAN: Thank you both for taking the time to talk to us today.

[MUSIC PLAYING]

PASCAL GELDSETZER: Thank you.

HELEN CHU: Thanks for having us.

FLORA LICHTMAN: Dr. Pascal Geldsetzer is an assistant professor of medicine, epidemiology, and population health at Stanford University. Dr. Helen Chu is a professor of epidemiology, allergy, and infectious disease at the University of Washington.

This episode was produced by Shoshannah Buxbaum. If this conversation sparked your interest, we want to hear from you. If you have a question or a comment, please call us 877-4SCIFRI is our number. Thanks for listening. I’m Flora Lichtman.

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