Boosters, Brain Age, and Other News

Harlan Krumholz: Howie, it’s great to see you, and welcome to Health & Veritas.

Howard Forman: You’re Harlan Krumholz.

Harlan Krumholz: And you’re Howie Forman. And we’re sitting together today.

Howard Forman: Exactly. We’re in the studio. We’re physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. This is one of our periodic episodes without a guest, and there is so much news to go over right now that it gives us an opportunity to catch up on a lot of things, some of them longer, some of them shorter. And I want to start off, Harlan, by wishing you a happy autumn.

Harlan Krumholz: Well, thank you, Howie.

Howard Forman: Yeah. And what comes with autumn?

Harlan Krumholz: What comes with autumn?

Howard Forman: Flu season.

Harlan Krumholz: Oh, okay.

Howard Forman: Flu season comes with autumn, and so we’re about to enter what we usually used to call “cold and flu season.” Now it’s “cold, flu, and COVID season.” I guess when we started the podcast, COVID was front and center. We talked about it an awful lot. We don’t talk about it as much right now, but it’s not because it’s gone or unimportant. In fact—

Harlan Krumholz: No. We’re just finishing a big wave.

Howard Forman: Yeah, no, exactly. It is still there. It’s still killing people, still hospitalizing people, but fortunately we have tools. We have tools to prevent it. We have tools to treat it if you get it. And last month the CDC did approve new boosters for COVID, which include two from the mRNA manufacturers—that’s Moderna and Pfizer—and one from Novavax, which is a protein-based vaccine. And while the three versions are targeting slightly different strains, most scientists believe that they are relatively protective to the degree that they need to be to keep everybody safe. And every month that goes by, by the way, highlights to me that our vaccination program has turned out to be safer than I once thought. And I know you’ve been doing some research about vaccine-related side effects, and I want to get your take on that.

But every time I’ve gone back to look at the issues that people raise, like “Is it safe in pregnancy?” “Is it causing an unusual number of cardiac deaths?”—all those things—the vaccination programs have turned out to be safer than I think we originally expected. And it’s not to say that we don’t have adverse events or idiosyncratic reactions, but study after study shows overwhelming benefit, and certainly more benefit than risk in all age groups, but especially older people and those who are immunocompromised. And for the record, I don’t know if I ever told you this last year—I probably did—but I went for Novavax last year and I’m going to go for it again. And for me, the side effect profile seems better. The evidence is that maybe it’s not as effective, but the side effects are better, and so that’s what I’m going to go for again.

But when I talk to people, and I’m curious to hear what you think, I tell people “Get vaccinated” for almost everybody. Maybe younger adults have a bigger decision to make, but if you are elderly or immunocompromised, you should be thinking about even getting a vaccination every four months or so as well, particularly during these peak periods. So that brings me to the Surgeon General of the state of Florida, which we talked about once before. And I hate to say this about anybody, and I’m not making an ad hominem attack, but he seems to be off the rails. I mean, it’s the only way to describe it.

Harlan Krumholz: What does he say?

Howard Forman: He has said that they lack efficacy. He said that they’ve been targeting the wrong viruses. He says that they’re unsafe. He talks about contamination of them. He has continued to use this rhetoric. He issued a release a week ago. We’re going to put this in the show notes. And our friends at Kaiser Family Foundation Health News came point by point, talking to many of our own colleagues, people that you and I know, going point by point of the things he raised and just talking about how ludicrous it is. These are not edge cases. This is not like, should you be vaccinating your twenty-year-old son? These are, do they work at all and should elderly people be getting vaccinated?

And again, we know that every drug has side effects. We know that everything we do, whether it’s food, devices, drugs, there’s unintended consequences, things might happen. But the evidence is so strong in favor, and hearing what he’s saying makes me think that this is all about just getting attention. So I’ll just say on my own, I’m reminding our listeners, go out and get vaccinated. Go look at the CDC website at the evidence, see if that helps you to make your decision. But schedule it now both for COVID and for flu. And if you’re elderly, RSV as well. I don’t know. What are your thoughts?

Harlan Krumholz: Well, maybe I’m not quite as an enthusiast as you are. I’m not against either. I’m just thinking that the virus is in a very different phase and many people are dying. About a thousand people I think in the last week have died of COVID.

Howard Forman: Week, I think.

Harlan Krumholz: I mean, we’re in the midst of a surge and people die. It’s an important risk for people. But for people who are healthy, I don’t know, what is the margin of benefit for these vaccines? And I’m also little confused. So it rolls out in the fall like flu. Well, flu is seasonal.

Howard Forman: Yeah, I know.

Harlan Krumholz: COVID is not seasonal.

Howard Forman: Right.

Harlan Krumholz: What is this idea—

Howard Forman: Or at least it has two seasons, maybe.

Harlan Krumholz: Well, at least it has two seasons, sometimes three. I mean, we have peaks. We don’t know what’s going to happen in the future. When should you get it? I mean, some people are of the mind that you really should be getting it about two weeks before you think you’re going to start getting a peak. Should you watch where it’s going to be spread because immunity—

Howard Forman: And we talked about that last year. That was sort of my thinking last year. I was going to wait. I was going to wait. At a certain point, you got to stop waiting. But it does seem, the evidence that has come out about the last set of boosters I think was about a 50% reduction in risk to individuals.

Harlan Krumholz: Well, of course, there were no trials.

Howard Forman: No. Exactly. You can’t do the randomized trials the way you had—

Harlan Krumholz: And people who are getting vaccinated tend to be healthier people.

Howard Forman: And people that may have had previous infection and certainly people that had previous vaccination. But what about you? You’re in a category that could get vaccinated, should get vaccinated. What are you going to do?

Harlan Krumholz: Well, I’m going to get vaccinated. By the way, flu vaccine I feel much stronger about, and I’m not even sure why I do, except that maybe as a cardiologist, there have been studies that show that flu vaccine is associated very strongly with reduction in cardiac events. People who are vulnerable, particularly for cardiac disease, heart failure and so forth, these people are vulnerable, and flu can tip them over. I will say, by the way, for people like that, I’m much more enthusiastic about the vaccine. I’m just saying for what do I do with my son, who’s 37 years old—

Howard Forman: But that’s why I’m saying “healthy.” I think those are edge cases and I’m totally open to that. And that’s why I said read the evidence, make your own decision. For me, as I’m approaching 60, I’m not in a category that says absolutely I should get vaccinated. I’m going to get vaccinated for the same reason I’m going to get flu-vaccinated. It’s about a 50% reduction in risk statistically over time. We have less evidence with COVID, obviously. With flu, we have a lot of evidence over time. Some years are better than others.

Harlan Krumholz: Yeah, but I do think it’s a decision people will make. As you know, I’m a Novid still, I haven’t been infected, so I’m thinking the vaccine might be even more important for me. I just don’t think we’re in the moment where we say everyone absolutely has to, regardless of your preferences and values.

Howard Forman: I don’t think so. And people need to understand that the CDC website, which recommends for all age groups: that’s all it is, is recommending. It’s not absolute. I think everybody should always make decisions about everything they put in their body, thinking about the risks and benefits.

Harlan Krumholz: And by the way, there are other vaccines that are also important. Pneumovax I think is very important.

Howard Forman: Yep.

Harlan Krumholz: Shingles I think is important. Are you getting RSV?

Howard Forman: I’m not getting RSV.

Harlan Krumholz: And why not?

Howard Forman: I don’t think it’s even recommended for me at this point. I don’t even think the CDC makes a recommendation of RSV yet for me.

Harlan Krumholz: Too young?

Howard Forman: Too young. I’m very young, Harlan.

Harlan Krumholz: You’re very young. Yeah.

Howard Forman: Thank you. Thank you.

Harlan Krumholz: Really fortunate.

Howard Forman: Thank you very much.

Harlan Krumholz: All right. I got my RSV.

Howard Forman: So what do you got?

Harlan Krumholz: Well, I wanted to talk a little bit about, there’s been a lot of news reports about a Commonwealth Fund report that went out, this report called “Mirror, Mirror 2024” was just released, and it compares the U.S. healthcare system to nine other high-income countries’ healthcare system. Spoiler alert.

Howard Forman: I know.

Harlan Krumholz: News isn’t great for America. I’ve been on this rant about this over the last 20 years. At the margin we’ve spent, I estimate, maybe 16 trillion more dollars above and beyond what we were spending. That is, we’re throwing additional money into the healthcare system. By the way, inflation-adjusted 16 trillion more dollars. And so despite spending more money on healthcare than any other country in the world, the U.S. ranks dead last when it comes to key measures like health equity, access to care, overall health outcomes. That means on average, Americans live shorter and sicker lives than people in countries like Australia, the UK, Netherlands. Now I’ve heard people say, “But that’s not everybody. If you’re wealthy in this country, you live....” Well, first of all, that’s part of the problem.

Howard Forman: It is absolutely part of the problem, but it is true. It is true that if you are in the upper class, if you’re in the upper middle class, we probably do have the best.

Harlan Krumholz: But we still lag in access, out-of-pocket costs. And by the way, health equity should bother everyone.

Howard Forman: Of course.

Harlan Krumholz: No matter where you are in this country. And so the report highlights several major issues. First, 25 million Americans remain uninsured. And many of those who do have insurance, so we talk a lot about underinsurance on this program, still struggle with all these out-of-pocket costs. As a result, a quarter of Americans can’t afford to get the care they need when they need it. This leads to delays in treatments, preventable deaths, lower life expectancy. On top of that, lower-income Americans face even more significant barriers, meaning healthcare is not only expensive but the quality tends to be unequal. So you add that on top of this issue of access itself. You and I are well connected, even when we want to get appointments or we want to get things done, we have to pull strings.

Howard Forman: Not easy.

Harlan Krumholz: We have to call people. Imagine people who have no power in the system. There was a conference last week that the Department of Medicine ran around health equity issues, and time and time again, speaker after speaker sort of pounding these issues. I’ll say it’s not all bad news. We ranked second in what the report calls care processes. This includes things like preventive care, patient safety, coordination of services. So these are kind of the traditional quality metrics that people look at.

Howard Forman: Can we pause for that for one second? Because they specifically call out the things that you’ve had the biggest impact on when they talk about care processes. They talk about cardiovascular and cerebrovascular interventions. That’s your work. You’ve had enormous impact on it. I’ve said it before. But can you talk a little, I know you were about to, I think, before I interrupted you, the difference between process measures and outcome measures and structural?

Harlan Krumholz: The structural measures are, do you have the capacity within the system to do something? Do you have a high-quality hospital? Does it meet regulatory—

Howard Forman: Do you have an ICU?

Harlan Krumholz: ...requirements and thinking what’s your nursing-to-doctor ratio and so forth?

Processes are, do you do the right things? And then outcomes is, are the right things happening as a result? That would be lower death rates or lower complication rates, lower readmission rates. In cardiovascular disease, certainly for a long time we were elevating the quality of care, the processes that were occurring, and we were getting better outcomes. We’ve stalled a little bit actually in the last couple of years, but there was a lot of gains in there. And we rank well. I think what this report tells me is that we need to keep our foot on the gas for how well we’re treating patients, how well we’re providing this kind of care, but we can’t be indifferent to all the other forces that are also part of the performance of our healthcare system: The health equity, the access, the satisfaction, and overall health outcomes. I mean, I’ve said this for a while, on our watch, while we’ve done better, for example, in cardiovascular disease, life expectancy is actually going down in recent years. Not even counting the pandemic.

Howard Forman: But again, I’m just going to push back a little that, and this is a question my students ask me all the time as well. Isn’t that partly due to the fact that we have more obesity in the United States or that we have more freedoms in the United States? Sometimes in the state of Connecticut doesn’t have helmet laws for motorcycles. Isn’t some of that—

Harlan Krumholz: More guns.

Howard Forman: More guns?

Harlan Krumholz: More guns.

Howard Forman: Yeah. Aren’t some of that due to things that have nothing to do with healthcare but just have to do with the country?

Harlan Krumholz: Well, look, you and I are in healthcare. We can have a very narrow view and say, “Our job is only reactive. So our job is only when people actually get sick or get injured. How well do we do helping them get back up?” Or we can say, “Gee, healthcare is also about slowing the demand for healthcare services. And we should be paying attention to help people, for example, in the city of New Haven, in the county of New Haven, and say we are not successful if we treat every heart attack, but every year the heart attacks are going up. We can’t declare victory unless we actually get to the root cause of the problem and help people have longer, healthier lives.” Your students aren’t wrong. Those are part of the social determinants. Those are part of the context environment. But we want to, without telling people how to live their lives, create the opportunity for people to live longer and healthier lives. And that’s, I think, part of our job.

Howard Forman: Yeah, no, and look, the gun issue is a really key issue as well because I think about half of all gun deaths are suicides. Depressed person wanting to commit suicide without a gun available is far, far, far less likely to kill themselves.

Harlan Krumholz: And accidents at homes and just...

Howard Forman: Right. So many things. So it is depressing to me that we make so little progress. I think that’s either like their eighth or ninth release of this report, which they do every two or three years, and it doesn’t change much.

Harlan Krumholz: We’re not getting better. We’re not getting better. That’s a big deal. All right, so what else is on your mind?

Howard Forman: We talked about flu in the first segment. I just want to quickly remind people... we had a question on TikTok, somebody asked me, can I talk about the cases in Minnesota? And quite honestly at that moment, I didn’t know about the cases in Minnesota. Two children attending a regional fair in Minnesota were exposed to what is real swine flu. Meaning this is flu that—

Harlan Krumholz: Swine flu?

Howard Forman: Swine flu. Pigs that get a flu. Not the swine flu of 2009—that was a human flu, but this is a flu that really only affects swine. But because these kids got a little bit too close to the pigs, they got this flu variant that’s called H3N2v, for the variant, meaning that it’s not a typical flu that’s circulating—

Harlan Krumholz: Shouldn’t we know how this happens? I mean, a lot of people get flu, a lot of people go to fairs, a lot of people may be in prox. We have Guilford Fair this week—

Howard Forman: Yeah, exactly.

Harlan Krumholz: ... the pigs were around. But they don’t end up getting characterized. The variant of the virus doesn’t get characterized. How was it that these two kids end up getting characterized?

Howard Forman: So what happens is, they go through a flu test and because the CDC wants to track the types of flu that are circulating, they will serotype these. Particularly early on, you want to know what’s beginning to circulate. And they just randomly found H3N2, which is not the ones that they were expecting to see, and it was this variant, not the usual human-type variants that circulate. The kids did fine, they recovered fine.

Harlan Krumholz: They live on farms or they were at...

Howard Forman: They were at a fair.

Harlan Krumholz: They actually were, just like I said, they were at a—

Howard Forman: Literally at that. That’s what I meant. It was literally like—

Harlan Krumholz: Like a state fair or county fair.

Howard Forman: Exactly. I think one of them said they were “physically close” and one was “indirectly close.” I don’t know what that means, if one was actually kissing the pig, but something was going on.

Harlan Krumholz: No, no, like your kids are going up and petting these animals.

Howard Forman: No, of course! Yeah, I would! You bring me to a pig, I’m going to get... closer—

Harlan Krumholz: Okay. I don’t want to hear anymore.

Howard Forman: I know, I know. But anyway, it was just interesting. The good news is there is no evidence that this swine flu, this particular variant is circulating between humans. And again, for our listeners, what we worry about with H5N1, what we worry about with these swine variants, is they can transmit from an animal to a human. We’ve proved that. As long as they’re not transmitting between humans, we’re in a safe situation. So these kids have recovered, they’ve done fine, but I just wanted to clarify that for people who might be interested. And again, the current flu shots that are out there are trivalent flu shots. They have three different viruses they’re protecting against. That’s something that our CDC and FDA make a decision in advance about, have to figure out what will be the circulating variants. COVID, same thing, that’s a monovalent booster that we’re dealing with. Flu, it’s a trivalent booster that we’re dealing with. And at the moment at least, we hope that we have the right flu vaccine for the season.

Harlan Krumholz: So I wanted to take up another topic out of, let me just say it like this, tongue in cheek, “out of left field.”

Howard Forman: Yeah. Oh yeah.

Harlan Krumholz: You know what the 50-50 club is?

Howard Forman: I do.

Harlan Krumholz: You do?

Howard Forman: Yeah, I do. I used to be a big baseball fan and there was no such thing as even contemplating the 50-50 club, but now, it’s possible.

Harlan Krumholz: So people may have read that this... Los Angeles Dodgers, Shohei Ohtani, who was with the Angels before, came over to the Dodgers this year, who is a two-way player. I mean, he can be a pitcher and a fielder, batter, of course.

Howard Forman: A great pitcher and a great player.

Harlan Krumholz: Probably the greatest baseball player that has ever played the game. And this year when he’s recovering from an injury, so he’s not pitching this year, but he’s batting because of the designated hitter rule. And he enters the 50-50 club, which is 50 home runs—by the way, he’s already now exceeded that—and 50 stolen bases.

Howard Forman: I know.

Harlan Krumholz: And the reason this is so unusual is because the people who are usually hitting the home runs aren’t the speedsters who are—

Howard Forman: No. Rickey Henderson was I think 30-30 club or something. That was a huge deal 40 years ago.

Harlan Krumholz: And Canseco was 40-40. Jose Canseco, but he was taking steroids, so people discounted that performance. But Ohtani, here’s the thing I wanted to raise about this, Howie, because it is a magnificent achievement. And you watch him and he seems like The Natural. I mean he seems like he just is born to do baseball. And by the way, these home runs aren’t little piddling shots over the wall. I mean they’re going to the second deck.

Howard Forman: They’re monsters.

Harlan Krumholz: The other monster hits. And it just is a moment to reflect on what does it take to do this. And I started reading about him and from a very early age, he set a very high goal for himself. And he put together this thing called a goal matrix. I don’t know if you’ve seen this yet?

Howard Forman: No.

Harlan Krumholz: Where he was sort of saying, “My goal”—and this was from what time he was very early in his career—“was to be in the top draft list within one of the top teams.” And around this matrix he puts what are going to be his goals for himself. And he puts “building body, mental, humanity, lucky, breaking ball, pitching speeds of a hundred miles an hour in sharp movement.” And then he builds out from this matrix for each of these points about things he’s going to do to build on this. By the way, and the “humanity” is “charity, courtesy, trusted person, ability to continue, thanks, planning, a person being loved by everyone, and sense.”

Howard Forman: That’s great.

Harlan Krumholz: What I mean by this is that these things don’t happen by accident. In the same way that when you watch LeBron or Kevin Durant or some of these people, I mean the number of hours that they put in, the dedication to the craft, the sort of will.

Howard Forman: And the value system.

Harlan Krumholz: The will to be excellent. And so when you see someone like Ohtani, you think like, wow, that’s amazing. He’s accomplished something amazing. But what you don’t ever see is everything under the surface that it took to get there. And when I was reading this about him, I admired the accomplishment even more because it wasn’t just like he was born with this gift. He had a gift when he was born, but he grew and cultivated it, his craft. Anyway, well-deserved performance by him. Incredible and—

Howard Forman: Yeah. No, it’s exciting to... it draws people into baseball who might not have been interested in baseball before. The idea of a pitcher also being a fielder is just unfathomable. I mean in history, Babe Ruth is probably the only other one that was able to successfully do both, and even he gave up the pitching very early on.

Harlan Krumholz: Ohtani created this matrix first when he was 15 years old. And he basically took it upon himself to say, “I’m going to approach this with meticulous detail. I’m going to keep the goals to myself,” which was interesting, a certain humility about it, but be specific about time and measurement in order to get better. Anyway, I just had to admire it. I don’t know what it has to do with health, except that if we want to get better in healthcare, we also have to dedicate ourselves.

Howard Forman: And measure it.

Harlan Krumholz: And be very specific about what it is we’re trying to do.

Howard Forman: Yup. That’s right. That’s right.

Harlan Krumholz: All right, back to you. I promise you I’ll get back to healthcare.

Howard Forman: Yeah. So let me tell you about my frustration this week with a company that many people know, Aetna CVS. So I’ve been on a cardiovascular drug that you know very well called Flecainide, which is for my paroxysmal AFib. It’s extremely effective. I talk about it in class all the time because it used to be pennies per pill, generic drug. I used to say it’s just a miracle. It was expensive when it was called Tambocor, back when it was a brand drug. Very—

Harlan Krumholz: You know this drug has a jaded history.

Howard Forman: I do, because when I was an intern, it was pulled off the market for—

Harlan Krumholz: For people with left ventricular systolic... where their heart wasn’t functioning well and they were having arrhythmias, ventricular arrhythmias.

Howard Forman: And causing sudden death. So it’s not a small thing to imagine that I’ve been on a drug for 11 years that might have been pulled off the market.

Harlan Krumholz: Was repurposed.

Howard Forman: That’s right.

Harlan Krumholz: And found to be highly efficacious and is widely used now for an atrial arrhythmia, atrial fibrillation in people who have a normal—otherwise normal—heart.

Howard Forman: Which is thankfully me, and it’s been a great drug. So I’ve been getting this drug from Aetna, was costing a few dollars every three months to get it. Even before my deductible, it was not that expensive. By April this year it was $23.18 for a three-month prescription, which is not too high. It’s a lot higher than it was 10 years ago, but everything is more expensive. In June, it suddenly goes up to $39.16. Okay? It’s about a 50% increase and I’m—

Harlan Krumholz: $39.16 a month?

Howard Forman: Every three months.

Harlan Krumholz: Every three months.

Howard Forman: Very inexpensive still, but still, 50% more than it was just before. And then this month, $67.66 for the exact same thing. And so I became sort of livid over this. I start looking this up everywhere. And I have a high-deductible health plan, so I’m very sensitive to this. I can afford this. A lot of people might not be able to, so I looked at what the prices were everywhere else. Mark Cuban’s pharmacy charges $14.96 for the entire three months. GoodRx shows a range of prices from $20.67 up to $61.47. Again, without insurance.

Harlan Krumholz: So the GoodRX means that if you go to different pharmacies, you will get different prices?

Howard Forman: Yeah. They show you where the cheapest prices are at different pharmacies.

Harlan Krumholz: That’s always amazed me. Basically within one town, the price can range that much depending on which pharmacy—

Howard Forman: That’s right.

Harlan Krumholz: How can that even be?

Howard Forman: Because people anchor to one place, and they won’t shop around. So Costco might be the cheapest for this drug, and Walgreens might be the cheapest for that drug, and they count on that.

Harlan Krumholz: Wow.

Howard Forman: It’s terrible. So Aetna’s own site showed my drug for $50, not the $67.66. So I called them up about this. I thought for sure they were going to be, “Oh my God, this is just an error.” And they proceeded to tell me that it was probably because I hadn’t exhausted my deductible. And I quickly said, “If I haven’t exhausted my deductible in September, I certainly haven’t exhausted it in June or April, so that can’t be the explanation.” Which case they said, “Again, it’s probably your deductible.” Started to make me frustrated. I’ve elevated it. Escalated it for them, I’ve elevated it within Yale University. I know this will get solved.

Harlan Krumholz: Note to listeners, don’t get under Howie’s skin.

Howard Forman: Oh my God. But the point is, Harlan, this is going on everywhere. People are being taken advantage of without knowing it. Large corporations do things without caring about what the impact is. And I’m the guy that you don’t want to mess around with, but most people are not somebody you—

Harlan Krumholz: So let me ask you this. Would you be able to go to Cuban’s pharmacy and buy it? Would that count for your deductible?

Howard Forman: No, that’s the problem. So that’s the problem is if it didn’t affect my use of the deductible, of course the simplest thing would be to just start ordering from Mark Cuban.

Harlan Krumholz: Now why wouldn’t Aetna want to use the cheapest place that’s available?

Howard Forman: So Aetna is, as you know, three different organizations. It’s an insurance company, it’s a retail pharmacy, and it’s a PBM.

Harlan Krumholz: And PBM, yeah.

Howard Forman: They’re making money on all three angles to this, and so they have no incentive to make this work well.

Harlan Krumholz: Wow.

Howard Forman: They’re literally saying to Yale, “This is what it costs.” But they’re saying to their own retail pharmacy, “We’ve got a dumb guy over here who will pay a lot more for this than he should.”

Harlan Krumholz: That’s wild.

Howard Forman: It’s frustrating.

Harlan Krumholz: That’s wild. So we’ll have to stay tuned for the end of the story.

Howard Forman: Yeah. I’m confident that this will get resolved for me personally. I wish I was as confident to say that this is not going to occur again for hundreds of other people at Yale and across the country. It’s very frustrating. I will say to people, it does make sense to look at what you’re paying for things because there will be these irrational pricing discrepancies arising.

Harlan Krumholz: That’s amazing. Can I go off on something else?

Howard Forman: I’d love it.

Harlan Krumholz: All right, well look, there was an interesting article that came out in Nature Medicine that I wanted to talk about that kind of caught my eye. So this was some research on brain aging, which has got my attention. And if you’ve ever wondered whether aging affects the brain differently across the globe or why some people seem to age faster than others given with cognitive function, this study actually provides some insight. Researchers of the study use something called brain clocks. These are models that measure the difference between a person’s brain age and their actual chronologic age. So they’ll see what age are you on your birthday, but because they’ve looked at a lot of people, they’re able to make some assessment of whether or not your brain is aging faster or slower. And a lot of this is based on imaging studies.

So ideally these two ages should be very close. And when someone’s brain age is higher than their chronologic age, that suggests accelerated brain aging, obviously something we want to avoid. So here’s the kicker. The study found that brain aging is not the same everywhere. And they analyzed data from over 5,000 people in 15 countries, including Latin American countries and places like the U.S., Japan, China. They discovered people in Latin American countries have larger gaps between the brain age and chronologic age, meaning that they’re aging faster. And their supposition is that this is really about the environment, that several key factors probably are contributing to this. Well, there’s a lot more socioeconomic inequity and maybe higher levels of stress but also higher levels of air pollution, poor access to healthcare. And what they’re suggesting is, it’s creating this kind of brain stress that wears down the brain over time, and that living in areas with these unhealthy environment and context of lives can make it more difficult.

Now look, this is all predicated on, were those representative samples in those places around the globe and what kind of inferences can you make? But this tool of being able to now be able to look at the brain, be able to make some sort of assessment, not just for people who get all the way to dementia, but just to say, is your brain aging faster than you are? Or are there things you can do to make it age slower? And of course we’ve seen a lot of other things. Another point in this program, I’ve talked about the alcohol.

Howard Forman: That’s what I was going to ask you.

Harlan Krumholz: There continues to be a drumbeat of momentum around saying there’s no safe level of alcohol.

Howard Forman: That’s right.

Harlan Krumholz: And one of the things that’s also aging the brain faster is exposure to alcohol.

Howard Forman: That’s what I was going to wonder about.

Harlan Krumholz: They weren’t able to really pull that out in this study. But I think increasingly we’re going to be seeing what can you do to maximize your brain health in the same way we’ve been seeing this for around cardiovascular health. Because nobody wants to just live longer if you don’t have your wits about you. I think we’re going to see more and more of this. I’m not saying this is an authoritative definitive study, but I was interested in it and the way that they’re talking about these exposures. I’ll just say one last thing. There is, in cardiology, a growing area of environmental cardiology talking about how pollution, stress, noise, things in our environment that we’re exposed to are also accelerating cardiovascular disease and unhealthy aging of our hearts. I’m sort of seeing these parallels between heart and brain.

Howard Forman: I will say, I don’t know how well it correlates, but when we read head CTs, which I’m probably reading about 20 of them every shift, or 15 to 20 every shift, we always—

Harlan Krumholz: Do you notice this, that sometimes people say like, “Oh, this person looks like they’re—”

Howard Forman: We frequently will say, “This is a young-looking brain for someone who’s 80.” Or sometimes you look at somebody and you’re like, “This person’s 45 and their brain looks like they’re 85 years old.”

Harlan Krumholz: And what are you keying off of when you say that?

Howard Forman: It’s the size of the ventricles, the atrophy… How much the brain has shrunk.

Harlan Krumholz: Oh really?

Howard Forman: Yeah. I mean you see it, and look, there’s a huge range of normal. So we’ll see 40-year-olds that will look very old. We’ll also see 80-year-olds that look young. And I don’t know how well that correlates with dementia and other real outcome measures of aging, but we do see an enormous variation.

Harlan Krumholz: Yeah. Wow. That’s amazing. All right, what else have you got?

Howard Forman: So I wanted to ask you really quickly, I got a question from a guest last week about the AirPod hearing aid issue. And I just wanted to know from you, we talked about it a little bit, here’s what I came up with, and I’m just curious if you know differently. From what I understand, there’s a software part of it and then there’s a hardware part of it. Apparently there are some individuals that say even the existing AirPods, the ones that I have in my pocket right now, can use software to adjust hearing so that you can turn it into a hearing aid. The new thing that Apple is introducing, these AirPods Pro 2s, I think, are a different level with new software. Do you have any sense about what is making these different? What is the advance that Apple has made here?

Harlan Krumholz: Well, I think there are two things. One is that they went through regulatory approval.

Howard Forman: You mentioned that.

Harlan Krumholz: Authorization. I think that they went through and produced the evidence. But to me, the thing that was interesting was that they have the capacity to do a hearing test on you. So they are customizing the hearing aid for what you need based on how well you did on the test. I don’t want to say “how well you did.” It’s not like you pass or fail. People have different deficits.

Howard Forman: They have losses in different ranges.

Harlan Krumholz: So that this thing is able to make those kind of adjustments. But I thought that that was pretty cool.

Howard Forman: It is cool. I mean, the idea of actually having an input from you and a test and then applying that input back to augment your hearing in one frequency range or another, or multiple, is really impressive to me. But it was a question that was posed, and I’m still trying to wrap my head around it. I think in the next month or so, we’ll start to see the actual product out.

Harlan Krumholz: Well, it wouldn’t surprise me to have other people follow suit. I mean, the thing is Apple’s got deep pockets so they could spend. It takes a fair amount of investment to be able to pull the data together and present it to FDA and so forth. But I think what we’re seeing on the horizon is a lot of this kind of—

Howard Forman: Yeah. The future is really exciting.

Harlan Krumholz: It is exciting.

Howard Forman: What do you have to wrap this up, Harlan?

Harlan Krumholz: Well, there was just one other thing. We’ve talked a lot about these efforts to pull together large-scale primary care initiatives, you know companies that have... Oak Street’s one of them.

Howard Forman: Which is CVS Aetna, so it’s our theme for the day.

Harlan Krumholz: There were companies that formed that said, “We can deliver primary care more efficiently. We can be able to provide higher patient satisfaction. We can bring technology to bear on this.” But they were struggling a little, by the way, they’ve all sort of struggled. That Walmart has given up on this, Walgreens is having difficulty, VillageMD and so forth. And Oak Street, CVS Caremark bought them.

Howard Forman: Yep.

Harlan Krumholz: What came out this week was the Department of Justice leveled a $60 million penalty to them to settle kickback allegations. And I guess it’s called “allegations” because they sort of end up settling—

Howard Forman: They settle it without admitting guilt.

Harlan Krumholz: But what happened was that Oak Street in Illinois, I mean where they were doing this, was sort of working with agents and paying them $200 if they could bring someone to them with a warm welcome. I was trying to figure this out, Howie, because obviously when you go to an agent, you figure they’re going to benefit from selling you a certain kind of insurance, for example, or bring you to a certain kind of place. But I guess the idea here was that the patients really weren’t aware that there was this thing happening in the background and it tripped on federal regs around kickbacks. And by the way, it probably worked out really well for them because they grew tremendously by providing this kind of incentive to people to deliver people to them. But I think that patients, people when they were talking with an agent, were expecting the agent to be representing their best interests and weren’t aware necessarily that they were going to also benefit financially from—

Howard Forman: This is the chronic principal-agency issue in economics. You’re going to somebody who’s supposed to be an agent for you, but instead they’re a principal for the firm. And you’re just describing it perfectly.

Harlan Krumholz: Yeah. So anyway, I thought it was interesting. To me, it just told me how much they’re struggling to get people in and needing to do things like this rather than being able to say, “We’re providing better care” and having people flock to them on their own.

Howard Forman: Yep. No, I hear you.

Harlan Krumholz: As we know, they’re all having—

Howard Forman: It’s frustrating.

Harlan Krumholz: Howie, this has been a lot of fun.

Howard Forman: It is a lot of fun.

Harlan Krumholz: I always love being with you.

Howard Forman: Me, too.

Harlan Krumholz: And I hope the listeners have enjoyed this too. You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, email us at health.veritas@yale.edu or follow us on any of multiple social media.

Harlan Krumholz: Yeah, and we very much want to hear your feedback. Let us know how you feel about this episode or the episodes in general, or if you have questions. As you can see, Howie’s already asking questions about this. When you do that, it helps people find us. And we always appreciate knowing that there are people out there listening.

Howard Forman: We sincerely do. We look for the feedback. We love trying to answer your questions. And if you have questions about the MBA for Executives program at the Yale School of Management, reach out via email for more information or check out our website at som.yale.edu/emba.

Harlan Krumholz: Yeah, and you know we’re here in the Yale Studio, so I want to give a shout out to Ryan McAvoy—

Howard Forman: That’s right.

Harlan Krumholz: ... who does such a terrific job here and we so appreciate.

Howard Forman: We really do.

Harlan Krumholz: And thanks for our researchers, Ines Gilles and Sophia Stumpf, and to our producer, Miranda Shafer. Everyone should know that Health & Veritas is produced with Yale School of Management and the Yale School of Public Health, and we’ve got a great team.

Howard Forman: We certainly do. We really appreciate it. We appreciate them. Thanks very much, Harlan. Talk to you soon.

Harlan Krumholz: Talk to you soon, Howie.

Howard Forman: Thank you.