Herpes Zoster Vaccination and Incident Dementia in Canada

Dr. Margarita Fedorova talks with Dr. Pascal Geldsetzer about how the herpes zoster vaccination may have neuroprotective effects, potentially delaying or preventing dementia. 

Read the related article in The Lancet Neurology.

Disclosures can be found at Neurology.org. 

Podcast Transcript: 

Dr. José Merino:
This is José Merino, editor-in-chief of the Neurology Family of Journals. The Neurology Podcast provides practical information to neurologists and other clinicians to help them provide better care for their patients. Thanks for listening and have a great week.

Dr. Margarita Fedorova:
Hi, this is Margarita Fedorova and I'm a neurology resident at the Cleveland Clinic. Today, we're exploring a study that speaks to an idea that's been building for a few years now, that vaccination itself might be neuroprotective.
I'm here with Pascal Geldsetzer, a physician and epidemiologist at Stanford University. Pascal is the author on a paper published in the February 2026 issue of Lancet Neurology titled "Herpes Zoster Vaccination and Incident Dementia in Canada: An Analysis of Natural Experiments." What makes the study different is how they got at the question. When Ontario started publicly funding the shingles vaccine, eligibility came down almost entirely to date of birth. People born a few weeks on one side of a cutoff could get the vaccine for free, and people born a few weeks on the other side could not.
That left Pascal and his colleagues with two groups of older adults who should be alike in essentially every way, except their access to the vaccine. And they asked whether those groups went on to develop dementia in different rates. We wanted to bring Pascal to the podcast because this is a question our patients are already asking us in clinic, and because vaccination is one of the few things we can offer an older adult that might actually protect the brain. Pascal, welcome to the podcast.

Dr. Pascal Geldsetzer:
Thank you very much for having me.

Dr. Margarita Fedorova:
Let's start with a take-home message. If I'm rounding with a team tomorrow and I get to teach them one thing from your paper, one thing I want them to still remember six months from now, what should that be?

Dr. Pascal Geldsetzer:
I think it is that for shingles vaccination and dementia, we now have a body of evidence from observational data that we're usually never able to obtain in terms of the fact that we are able to get at cause and effect in a much more plausible way than we are usually able to. And we can say here now that shingles vaccination may well have a delaying or preventing effect on the dementia disease process.

Dr. Margarita Fedorova:
Before we get into your study, give us the background. We tend to think about dementia in terms of amyloid, tau, vascular risk, and lifestyle. Where do vaccines come into it? And is this really a shingles story or is it something broader about vaccination and brain health in older adults?

Dr. Pascal Geldsetzer:
Yeah, so unfortunately we don't know exactly. And so of course, broadly speaking, it could be either through reducing reactivations of the chickenpox virus or varicella zoster virus, which we know is a neurotropic virus, which we know reactivates throughout life. And so reducing these reactivations and probably accompanying neuroinflammatory processes may well have benefits. But there may also be a broader potentially virus-independent immune mechanism at play here that may also apply to other vaccines than just shingles vaccination. So we don't really understand the mechanism yet. It's a very interesting and fascinating area of research and hopefully we'll learn more in the future.

Dr. Margarita Fedorova:
We already knew from a lot of prior work that shingles vaccine was associated with a lower risk of dementia, but in the paper you were direct that those earlier studies can't really speak to cause and effect, and that's a really big part of why this one matters. What goes wrong when we simply compare vaccinated people to unvaccinated people and how does your design get around it?

Dr. Pascal Geldsetzer:
So this gets to the fundamental problem that we usually have in observational data analysis in epidemiology, right? It's that those who get a certain intervention, who get a certain medication or who decide to adopt a certain lifestyle regimen, certain diet, or who decide to get vaccinated are just very different to those who don't. And especially in the case of vaccination, we know there's this healthy vaccinee bias whereby those who have better preventive health behavior, health motivations, et cetera, are the ones who go get vaccinated and they have a lower risk of dementia in any case regardless of vaccination. And we can try to adjust for these differences between these groups. And that's what we do in epidemiology with all sorts of fancy methods. But at the end of the day, what we're restricted to is the information that we have in the data sources that we're analyzing.
And I just don't have very much information at all in electronic health record data, medical claims data, et cetera, on all these various health behaviors, health motivations, dietary behaviors, et cetera, et cetera. So it becomes really hard to know whether we are really truly able to adjust for all of these differences. What we are doing instead in these shingles vaccination natural experiment analyses is we're changing the comparison group to something that's much more close to what we have in a clinical trial. And of course the clinical trial is what we need to ensure that the comparison groups are comparable because we know all that's different about them is whether a coin landed on heads or tails. And here in our natural experiments, we know that all that's different about the groups that we're comparing is whether they happen to be born essentially by random chance a few days earlier or a few days later because our natural experiments are exploiting these date-of-birth-based eligibility rules for shingles vaccination.
For instance, in Wales, in our first paper that we published in this series, we know that those who had their 80th birthday just prior to the start date of the shingles vaccination program, which just so happened to be September 1st, 2013, were ineligible and remained ineligible for life. Well, if you had your 80th birthday just after, you were eligible and we see a jump in your probability of ever getting the vaccine by just a week's difference in birth from 0% to 50%. So we have now this really sharp contrast just by the fact that you were born a few days earlier or a few days later. And that's what makes our comparison groups different and the effects that we're seeing much more likely to reflect true cause and effect rather than just a correlation.

Dr. Margarita Fedorova:
And for this current natural experiment, what exactly did you find? Without talking too much about the numbers, can you tell us whether we think we're preventing dementia or delaying it with the vaccination?

Dr. Pascal Geldsetzer:
We don't know exactly if we are preventing or delaying dementia. That's an active research area in my group to truly understand this. But what we're seeing is that these groups of people were born just on either side of this eligibility cutoff. Those who happen to be eligible because they were born just a little bit later have a lower probability of receiving a new dementia diagnosis in the future. It's hard to pinpoint the exact magnitude of the effect because our method really zooms in on people born just around this cutoff. And of course also various data limitations that we usually run into such as having knowledge on your exact vaccination uptake levels in these two groups dementia and ascertainment, et cetera. But what we can say is that there seems to be a large, certainly clinically meaningful protective effect for dementia in the future.
We always have to bear in mind the intervention here is a simple one-off inexpensive safe intervention that's already recommended in any case for shingles prevention. So the bar that this intervention has to pass in terms of showing efficacy is much lower because the downsides are so low. This is a really exciting, for me at least, it's a really exciting area of research.

Dr. Margarita Fedorova:
I wanted to circle back to you talking about randomized trials. So is a trial potentially the right next step here and what would one have to look like to settle this question?

Dr. Pascal Geldsetzer:
Yes. So that is the dream that I'm currently pursuing, trying to see if we can get the funding together for a clinical trial of the shingles vaccine that we have been studying in all our natural experiments, which is an off-patent shingles vaccine. It's the old live attenuated vaccine and may well be specific the effects that we're seeing to that vaccine. So just to reduce uncertainty using that vaccine is important. But that also means for funding, we really have to try to see if we can get philanthropic funding, private foundations. So yeah, that's what we're hoping for somehow. But yes, really to conclusively test this question, this link, what we need at the end of the day is a clinical trial and also to convince the medical and public health community. And also because it offers just really important opportunities to learn more about this link that we can't in observational data analysis.
So it's a trial that would be ambitious in terms of its sample size because we do need here, we have the evidence for dementia prevention and that means we need a large sample size to be able to have enough events. However, we already start seeing survival curves for dementia incidence separating after about a year and a half or so, a year and three months. So a four-year follow-up period, for instance, would be reasonable. And so it's not a trial that would need to take decades. And yes, that's what I'm pursuing at the moment.

Dr. Margarita Fedorova:
I do want to briefly talk about any important caveats that we have in this project. I'm thinking in particular about the sex difference since the effect looked stronger in women, and I suspect that this is one piece that people will latch onto. How much weight should we be putting on that?

Dr. Pascal Geldsetzer:
Yeah, it's something that we tend to be seeing in our data sets that there are stronger effects, stronger protective effects among women than among men, but it doesn't mean that men do not benefit. And there's also still some uncertainty as to really how large or important this difference is between the sexes. It was particularly marked in our first analysis, but that was a bit of an outlier in terms of that relationship.

Dr. Margarita Fedorova:
I also wanted to talk about what to do with this in terms of clinical practice and specifically patient counseling. Most of us in neurology don't think of ourselves as the people responsible for patients' vaccination. Should we be? And is there a case for a neurologist asking an older patient or patient with cognitive complaints whether they're up to date on their shingles vaccine?

Dr. Pascal Geldsetzer:
It is a recommended vaccine for adults 50 years and older in the US. We know it prevents shingles. We know shingles can have a variety of complications. There's also some evidence that shingles vaccination potentially has benefits for cardiovascular and cerebrovascular disease risk reduction. So putting all of this together, I know clinicians are busy and that is probably the downside, having the bandwidth and taking the time to do this, but I certainly think it can't hurt to check on vaccination status, to recommend vaccination in those who are eligible for the vaccine. And for dementia, we can say now that there may well be benefits also for dementia, for cognitive health in older age.

Dr. Margarita Fedorova:
And in terms of the underlying mechanism of the vaccine, there was a paper last year on the AS01 adjuvant that raised the possibility that the benefit isn't entirely about the virus, but more about what the vaccine does to an aging immune system. If that turns out to be right, it would say something much bigger about vaccination in older adults. Where does your instinct land?

Dr. Pascal Geldsetzer:
It's hard to say. I'm probably the wrong researcher to ask about this because I don't look at basic science so much. I'm really more of a data cruncher, but certainly it's a possibility. We know these broader immune mechanisms are important for vaccines and seem to vary by particular types of vaccines. We just don't know yet to what degree they impact on chronic diseases, these broader mechanisms, including dementia. There's a strong case to be made as well, of course, for something specific to the varicella zoster virus, given that we know these neurotropic herpes viruses are in this constant interplay with the immune system, cause these neuroinflammatory processes, and that this poses some sort of chronic immune stress that drives inflammation in the body is something that, and that could be particularly important in older age as the immune system weakens. It's certainly something that seems to me at least very plausible as well from a biological perspective.

Dr. Margarita Fedorova:
So let's say I have a 72-year-old in clinic next week. She's read a headline about the shingles vaccine and dementia, or maybe she's hesitant about vaccines in general. What is a fair and honest thing for me to tell her? How would you use this evidence in that conversation without overselling it?

Dr. Pascal Geldsetzer:
Yeah, so of course I'm a researcher. I try to shy away from making vaccination recommendations, but practically speaking, I would certainly say it's safe to say that the shingles vaccine is a recommended vaccine for older adults. We know it prevents shingles and its complications. And we now have an additional body of evidence that suggests that the vaccine may also have benefits for dementia for cognitive health in older age. That is a very fair thing to say.

Dr. Margarita Fedorova:
Thank you so much. I've been speaking with Pascal Geldsetzer from Stanford University, who's a senior author on a paper published in the February 2026 issue of Lancet Neurology titled "Herpes Zoster Vaccination and Incident Dementia in Canada: An Analysis of Natural Experiments." Thank you for your time and insight today.

Dr. Pascal Geldsetzer:
Thank you. Thank you so much for having me.

Dr. Stacey Clardy:
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