CEimpact Podcast

Does the Shingles Vaccine Delay Dementia?

August 19, 2024

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Dementia is the 6th leading cause of death in the U.S. and there hasn't been a lot of hope with prevention or treatment. However, recently published evidence suggests the shingles vaccine may delay it's onset.
 
The GameChanger
Several studies suggest a delay in onset of dementia with the recombinant shingles vaccine.
 
Guest
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
 
Reference
The recombinant shingles vaccine is associated with lower risk of dementia

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CPE Information
 
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Describe dementia's epidemiology and the significance of preventive interventions.
2. Discuss the strengths, weaknesses, and outcomes of the study.

0.05 CEU/0.5 Hr
UAN: 0107-0000-24-246-H01-P
Initial release date: 08/19/2024
Expiration date: 08/19/2025
Additional CPE details can be found here.

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Speaker 1:

Hey, ce Plan members from CE Impact. This is Game Changers. Did you know the CDC now says that dementia is the sixth leading cause of death overall and the fifth leading cause of death for adults over age 65? It continues to rise and devastate patients and their families. There have been few interventions that have shown to prevent dementia and Alzheimer's disease. However, there is a new study showing a little bit of hope. So I say a little bit of hope and we are going to gleam onto anything that shows a little bit of hope. So, surprisingly, it has to do with the shingles vaccine. So we're going to talk about that today. On this Game Changers and I've been excited about this topic for a while. We've had it on our list so I'm happy to get into it. So here to talk with us today is our resident expert, Geoff Wall. Dr Wall, what can you tell us about why this information is important right now?

Speaker 2:

Thanks, jen. Yeah, this is a kind of interesting study and of course we don't want to overplay things, but I think this is this is this is, I think, the best study to date that suggests that there probably is a link between zoster and the development of of at least some types of dementia and that, yeah, maybe you know, being vaccinated might be helpful. So this is a study that's garnered a lot of lay media attention, like all things that have to do with Alzheimer's. I think, you know, a lot of lay media outlets kind of pick this up and I think that's why we chose this for a game changers, because I suspect that a lot of pharmacists and providers are going to get questions about this stuff. So, you know again, you know, a quick, you know, review of zoster. You know again, we, we, you know know, that that you know.

Speaker 2:

The zoster vaccine, especially the recombinant zoster vaccine that has been out since 2017, is unbelievably effective at reducing not only the incidence of shingles but, I think, more importantly, the incidence of post-herpetic neuralgia, which is really the long-term issue that to date, we know is associated with shingles. It's actually recommended by ACIP for, basically, you know, all adults over age 50 or 60, certainly 60. And then you know there's evidence, certainly down to 50, that Shingrix should be given to all these patients. If you've ever had shingles, you know how painful it is.

Speaker 2:

I've known a lot of people who've had it. They've compared it to some of the most painful stuff they've ever had in their life. And then unfortunately, as I said, there's a percentage of patients who, even after the lesions crust over and go away, they still have post-repetiton neuralgia which is very difficult to treat. And now you're on all sorts of medications for neuropathic pain and stuff like that. So I think that's the.

Speaker 2:

You know, you know taking everything aside, obviously, the benefit of of shingles vaccine, just in preventing shingles is a pretty big deal. But now this study comes out and kind of talks about, you know, what would be the role of shingles vaccine. You know, is there an association between that and decreased risk of dementia, as you point out, jen? You know it's again, it's. It's a huge cause of death and, if you know, alzheimer's disease is the one we most think of the most commonly. But there are actually numerous kinds of dementia. There's, you know, frontal lobe dementia, there's Lewy body dementia, there's all sorts of stuff and they all really kind of have one thing in common is that we really don't have good treatments for them and even prevention is really kind of iffy. So you know, as you point out, it's a leading cause of death.

Speaker 2:

It's also very, very expensive. Cost economies globally 1.3 trillion that's with the T US dollars, and of course the vast vast majority of that is cost provided to caregivers, right? So either family members, close friends or nursing homes and stuff like that. And some studies suggest that with advanced dementia, that patients require at least five hours of direct care and supervision a day. So you know, again, that's a huge cost, that's a huge burden on the healthcare system and it's a huge burden on family members, both emotionally and financially. Women are disproportionately affected by dementia, as I think we know, probably because a lot of it is that they live longer than men, that they live long enough to develop dementia, but still it's something that we've seen. As far as treatments, you know, we in past Game Changers, we've talked about some of the new anti-Tau monoclonal antibodies that will come out and I have not been a big, I have not been particularly impressed. I think the evidence suggests that it may slow down the progression of Alzheimer's, but at the risk of the development of head bleeds, which isn't good. As well as the enormous expense associated with the drug, somewhere in the order of about $50,000 a year. The cost, that's just a right cost. We aren't talking about the indirect costs of frequent MRIs to look for head bleeds and stuff. So I mean, I think you know, I think there's a reason why FDA was kind of on the fence about approving those medications, you know. And of course we've got the old standbys like denepazillamamantine, which, again you know, really you know may slow the progression of dementia but really don't actually prevent things like going into the nursing home. You know they may slow some of the numbers associated with dementia, but that's really about it. So, you know, instead of treatment, people have turned to prevention and again we don't have any really good you know evidence that drugs of any sort actually slow or reduce the risk of cognitive decline. So basically, it's all the healthy stuff that you should do, right, you should be physically active, don't smoke, don't drink excess alcohol, eat a healthy diet, maintain normal blood pressure, because one of the most common causes of dementia is hypertension, when people get small vascular dementia and stuff like that.

Speaker 2:

Probably the biggest studies that have shown prevention is basically keep yourself active. People who lay around and watch television all day long are, frankly, more likely to develop dementia than people who keep their brains active through reading, puzzles, etc. Etc. Again, a lot of our apps out there are trying to really push that. Maybe they're not so bad as long as you're not paying a lot of money for them. The bottom line is keep your brain going and it just decreases the risk of dementia.

Speaker 2:

There are no drugs that have been associated with the acoustic dementia, so you know anything that that is a drug or a vaccine that may do? That is going to generate a lot of the information, and we've known for decades or at least associated for decades that that, uh, zoster may be associated with dementia. Uh, if this has not been proven, obviously, um, but obviously. But the association between zoster directly causing dementia has been postulated for decades now, and previous studies have, you know, taken a look at this and said you know, yeah, gee, it seems that people who are vaccinated seem to be at lower risk. The problem with all these studies, of course, is there's bias, because they've studied, basically, people who are vaccinated versus people who weren't vaccinated, and people who are vaccinated are just more likely to live healthy lifestyles, they're more likely to have a better insurance.

Speaker 2:

They're more likely to have a higher socioeconomic status, et cetera, et cetera. So the association was there, but it was always somewhat suspect because of the risk of bias. So the authors of this study and we've got a link in the show notes did something pretty cool. I wish I would have thought of it myself, to be honest with you. And they said well, you know, we have the opportunity to do a natural experiment here because, as we all know, there's been two shingles vaccines out in the last decade.

Speaker 2:

The first was Zostavax, and Zostavax was used pretty extensively. The problem with Zostavax was that it was a live vaccine so, again, a lot of people couldn't take it who couldn't take live vaccines and it wasn't that effective. It didn't do a very good job at preventing shingles or post-herpetic neuralgia. That effective. It didn't do a very good job at preventing shingles or post-herpetic neuralgia. And so when the recombinant vaccine came out in 2017, shingrix, it was far more effective, more like 85 to 90% effective in the first five years of preventing shingles and post-herpetic neuralgia. And, as you might imagine, as soon as that vaccine became available, pretty much everybody who could switch did, and so there's this kind of natural experiment they could do where they would look at patients who got the shingles vaccine before that 2017 release of.

Speaker 3:

Shingrix.

Speaker 2:

And then a period after that where almost everybody was on Shingrix. So, you know again, you know, give these guys props for kind of thinking ahead and saying you know, this is a way to kind of you know, take a look at this and minimize that healthy patient bias sort of thing. So this was a large database study. They used the Trinic X collaborative network database. 62 healthcare organizations, health hospitals, primary care specialists, over 100 million patients are involved with this and the these healthcare organizations basically just supply de identified healthcare information, including demographics, diagnoses, medications and a wide variety of other stuff. And so the authors basically took this data from the Trinet X database to try and figure out kind of this answer. And so you know what they did basically was they compared patients who got the shingles vaccine or the Zostavax vaccine from 2014 to 2017. And then they looked at patients who received the shingress vaccine from 2017 to 2020. To be in the study, they basically looked at older patients and that was really about it. So I mean, there wasn't a lot of exclusion criteria, anything like that. Then they did as you might imagine, with these kind of studies they had to do a propensity match score. So what they did was they took a look at patients and tried to match them as closely as possible for a pretty big number 60 covariates. So they really tried to minimize bias by matching patients, again on a scale of 60 covariates, including comorbidities, things like diabetes, a history of previous herpes infection, history of influenza, vaccine, age, socioeconomic factors, race, marital status, you know, etc. Etc. Etc. We won't spend a lot of time talking a lot about that, but basically, you know, trying to match these people together to kind of figure that out. In the end they had a matching number of patients of 103,000 individuals who received a first vaccination of Shingrix between 2017 and 2020. And then again they propensity matched those two patients who received Zostavax from 2014 to 2017. And they followed these patients forward in time about four years. So again, that's why the paper was just published, because they followed from 2017 to 2020, basically. So now we're kind of four years out.

Speaker 2:

Basically as far as demographic data on these patients, the patients were in their 50s and 60s, as you might imagine. Again, the follow-up was about four years. The majority of patients were females and then that was really about it. I mean, there wasn't a whole lot of differences between the groups and what they basically found was that there was a statistically significant decrease in the development of dementia between patients who received Shingrix compared to those who received Zostavax and so and that was a hazard ratio of 0.83, and the 95% COPS interval did not cross one. So you know was statistically significant. When they did a deep dive in the data, it looked like as far as preventing Alzheimer's and only minimally did that, and what it actually did was it translated into 17% more time lived, diagnosis free. So in other words, you know, when they match patients who ended up getting dementia, the actual number of patients who got dementia between Shingrix and Octobass really wasn't that much different. It was a little bit lower in the Shingrix group, but that didn't reach statistical significance.

Speaker 2:

What did reach statistical significance was the amount of time lived without the diagnosis put in the chart of them having dementia, and that translated into about six months, about 164 days among those who were affected with dementia. So you know, does the Shingles vaccine prevent dementia or is it associated with prevention dementia? Maybe minimally, but what it does seem to do is prevent the development of dementia or at least the worsening dementia over time. This was true across all types of dementia, except for Lewy body and frontal temporal dementia, which again kind of makes sense because those types of dementia are different from Alzheimer's. So kind of makes sense because those types of dementia are different from Alzheimer's. So that kind of makes sense.

Speaker 2:

Those vaccinated after 2017 were less likely to have a herpes zoster vaccine or infection. Big surprise, because again, we know that Shingrix is more effective than Zostifax was. There was no difference in all cause mortality. But when they did all these other covariates, it was basically found in all the different covariate groups, basically. So when adjusting for socioeconomic factors, age, gender, race, everything else, it found that they were similar. And, interestingly, one of the covariates they looked at was influenza vaccination, because, again, is this just a vaccination effect or is it specifically targeted disaster. And they found again that shingles vaccines both of them were associated with a lower risk of dementia compared to patients who either received the influenza vaccine or the Tdap vaccines. And again the numbers were very similar, kind of across the board about 20% decrease. So it looks like it isn't vaccines in and of themselves that prevent dementia. It looks or may prevent dementia or delayed the onset of dementia. It looks like it's actually specific to shingles vaccine. So that's kind of interesting.

Speaker 2:

So you know, again there's been a lot of experts who've kind of weighed in on this. I was kind of reading some of the editorials in this and some of the other kind of big medical websites and again everyone's kind of cautious. No one is probably going to get the Zoster vaccine to prevent dementia, right. It's like, well, I don't really care about getting shingles, I just don't want to get dementia. That's probably not going to happen, right. But it does suggest that if you are on the fence about getting the shingles vaccine and I really don't know why anybody would be you know this may be an added benefit that at least we're going. You know this is the best data we're probably ever going to get on this. There's never going to be a randomized control trial on this, obviously. So this is really probably the best data we're going to get, suggesting that there may be an added benefit to receiving Shingrix, in addition to just preventing shingles. You know, as anyone who's received the vaccine will tell you, it's kind of painful.

Speaker 2:

Some people are kind of nervous to get that because of it I get that and I totally understand, but in my opinion this is just one more reason really to think about getting the Zoster vaccine.

Speaker 1:

So pretty simple, pretty easy. You know, yeah, I mean I totally agree with you. And when you said I don't know why anybody wouldn't, it's because they're I mean, they're painful. Well, right, like you know, there's a lot of hesitation. I think about it and I think people put it off, and you know I was going to talk a little bit about that. In terms of vaccine hesitancy, I think this is huge. I mean, this is everybody's scared of getting dementia. You know we're all playing those games on our phones and you know, reading about it constantly and looking for, you know, what's going to be the breakthrough that you know prevents that, because none of us have that. So I think, in terms of vaccine hesitancy, this is a huge thing in our arsenal where we can say there has been evidence that it prolongs dementia and maybe that's the thing that tips people over the edge to say, okay, yeah, I'm going to get it. So I think that's, I think it's really important information for pharmacists to have and to utilize that in some of your conversations.

Speaker 2:

Yeah, no, I agree, and you know, as everybody knows, you know, vaccine hesitancy is kind of at an all-time high. You know we could spend you know hours talking about why that is. But you know, I think that you're right that I think that there is some hesitancy. I personally know I'm kind of of the age where I know people who are getting this or are thinking about getting it, and probably, you know, you know, like you Jen, when anyone ever asks you, yeah, well, absolutely you should get it. No doubt about it.

Speaker 2:

You know, there we have very few vaccines that are 90% effective over the course of at least five years. And so you know, and again I mean people who haven't had shingles don't understand how painful it is. I mean it is. You know it is like I said, I've had friends who have just said, you know, it's the worst pain they've ever had in their life. And these are women who have had babies. So it's like, okay, good to know. You know, yeah, I'm not. You know I'll take a little bit of pain in two shots to deal with that. And even coverage I've not heard of too many insurances that don't pay for the shingles vaccine.

Speaker 2:

I think you know this is. You know it's pretty universally covered. So really, the you know the hesitancy comes from, gee, you know, I'm just not sure I want to get another vaccine. Gee, I've heard it. My friends tell me it really hurts, et cetera, et cetera. And yeah, if this piece of information says, okay, look, you know, if not getting shingles isn't enough for you, if that isn't enough on the table to consider it, you know, perhaps the you know the fact that you know, at a minimum, while it may not prevent dementia, you know how would you like to live another six months without that diagnosis. You know, and that's really what this study kind of showed, yeah, yeah, absolutely.

Speaker 1:

I think it's super powerful. If Jake were here, he would talk about the health equity component. He'll be proud of us that we're going to address that. But you know I think you mentioned that that there wasn't, you know, a difference across socioeconomic. But again, I think it's just the vaccine hesitancy and just asking the question you know, are you up to date on your vaccines? This is where you should be. These are the ACIP recommended vaccines at your age. You know, have you gotten them?

Speaker 1:

Let's you know, let's make an impact on that in pharmacy. I think that is such a huge opportunity for us. We can ask that question every month when they come in to get medications refunded.

Speaker 2:

I think that's the key is that you know there are a lot of. You know, again, I'm, I would like to think that most primary care docs are addressing this with with their patients. But but yeah, as you point out, you know they get a once a year, once every six months sort of ability to do that. But, yeah, you know, every time you come in and go, you know, hey, you know, you know, I noticed that you're 55 and you've not, according to our records, you haven't received this. Would you be interested? You know, and eventually, I think there are going to be a cohort of patients are like, okay, okay, you know, this is the sixth time you've asked me. I get it, let's, let's go ahead and do that. You know, and, and yeah, I mean you know, I think if you can capture even 10, 15% of those patients, it's going to make a difference. Yeah, so, no, I mean, you know, I think we're, I think we're going to see more and more of this.

Speaker 2:

You know, again, the the Holy grail, and this is actually a vaccine to prevent. You know, and there, fact is, is I'm not sure what you know, barring some gigantic breakthrough that you know something, that you know a way to approach Alzheimer's. That's just completely different than what we think about the pathophysiology. Now I'm not sure we're ever going to come up with with a treatment that significantly stops the progression of cognitive decline, and so prevention is going to be the way to go here. And, and you know, again, I think, I think that we are a long, long ways away from saying, okay, well, grandma's starting to forget stuff, let's go and start her on this med so that she doesn't get any worse. Yeah, we're a long ways from that, and so anything we can do to delay or prevent you know that's not, you know, drug related, I think, is huge.

Speaker 1:

Yeah, yeah, absolutely. Well, this is, this is a huge step towards that. I agree and has other benefits as well. So that's the bonus. Ok, well, thank you, Geoff. Thank you so much, dr Wall. I appreciate you being here with us this week yet again, appreciate you being here with us this week yet again.

Speaker 1:

No problem, that's it for this week. If you are a CE plan member, be sure to claim your CE credit for this episode by logging on at CE impactcom. And, as always, have a great week and keep learning. We'll talk to you next week.

Speaker 3:

Thanks for listening. Then claim your CE credit by clicking on the link in the show notes and check out CE impacts other education at CE impactcom, where we curate the most important information in pharmacy and medicine to deliver straight to you. Join today to connect your learning to practice you.