Ep 80: George Vradenburg and the Global Impact of Alzheimer's (part 1)

Alzheimer’s is not just an aging issue, but a lifelong brain health challenge that has major global, economic, and societal implications. George Vradenburg, Chairman and Founder of UsAgainstAlzheimer’s, who has incubated satellite organizations globally to address these issues, debriefs BrainStorm host Meryl Comer on the recent launch of “Brain House” at the Davos World Economic Forum. Together they explore the potential role of AI in enhancing brain capacity, the fragile state of Alzheimer's research funding, and the business case for diverse representation in clinical trials. You don’t want to miss this leadership episode.

Produced by Susan Quirk and Amber Roniger.

Transcript

George Vradenburg (00:01):

Depending on how you think artificial intelligence is going to develop, it either can be seen as an extension of the human brain and an extension of our own power to be creative and to think of problems. Much like when I was going into high school, I changed from slide rules to a little handheld calculator, right? So all of these little devices can potentially enable the human brain to focus on more creative things, more empathic things, a variety of social things, or it could be our enemy because it's attempts to substitute for the human brain.

Introduction (00:38):

Welcome to Brainstorm by US against Alzheimer's, a patient-centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver and Emmy award-winning journalist and the author of the New York Times bestseller, slow Dancing With a Stranger.

Meryl Comer (00:54):

This is Brainstorm and I, Meryl Comer. Joining us is George Vradenburg, Chairman and Founder of UsAgainstAlzheimer's, convener of CEOI, the global CEO initiative against Alzheimer's DAC, the Davos Alzheimer's Collaborative and Chair of GAP, the Global Alzheimer's Platform Foundation. And just for transparency, we've been in the trenches together for decades. Welcome, George. Always great to catch up. You've just returned from Davos and the successful launch of the Brain House. What's that about? How was it received?

George Vradenburg (01:32):

I'll tell you who decided to put an annual meeting on the side of a mountain in January when it's ice and snow and miserable. I'll tell you this man, Klaus Schwab was either a genius or a devil. I have a real love hate relationship with this conference because it's such a challenging environment. Davos this year was really quite interesting. Obviously in the world there's a lot of disruption because of the election of Trump political instability in Korea, political instability potentially, or change in Canada, in France, in Germany, potential trade wars. So a lot of that was clearly on Davos agenda. But this year, the Brain House was something that the Davos Alzheimer's Collaborative put together with a number of partners to try and draw the world's attention to the challenges that we're facing with brain health around the world. Brain disorders are now the number one disability creating health problem around the world, and there are estimates that vary between five and $8 trillion of lost productivity.

George Vradenburg (02:34):

As a result of that, it's simply going to be impossible to maintain global wealth that we have been able to sustain because we'll have fewer people trying to support older populations and larger populations. So we are trying to bring attention to this challenge of brain health in both of its scopes, both in terms of health and the absence of brain disorders, but more importantly potentially in terms of the resilience of the workforce. So whether we are now turning from brain health and including within that scope, brain productivity, brain capital, brain economy, it turned out that this year Davos brought forth this unique and distinct and very impactful message about the importance of brain health. So

Meryl Comer (03:15):

George, has brain health become an economic and societal imperative and not just a health issue? And do you see this as a critical pivot and a forecast of how the global response to Alzheimer's will be evolving in the next decade?

George Vradenburg (03:31):

I think Davos this year is a critical turning point, a critical pirouette in terms of putting together a wide variety of converging challenges and mega trends and centering it on the importance of the brain for Alzheimer's. We've learned over the last several years that Alzheimer's is the culmination of a wide variety of risk factors that occur during your course of your entire life, from a lack of childhood education to mental illness in your teens and twenties and mental illness in midlife, cardiometabolic factors in midlife. All of those accumulate through your lifespan and risk your health later in life. Because we are living longer, our lifespan is longer, but our brains span is not rising at the same rate as our lifespan. So we're finding that there are all these factors during the course of life that are critical to whether or not you get Alzheimer's and whether or not your brain can resist it. So Alzheimer's is a movement now, not just of that little old lady in our rocking chair in the corner

Meryl Comer (04:33):

Listening to you. It sounds more like a holistic shift in focus to a brainspan lifespan connection.

George Vradenburg (04:40):

It is a cumulation of everything from fetal neurology to first thousand days of life when all of your synapses are put together except for the frontal cortex, which is your judgment and your emotions, which as we know from teenagers, doesn't really get formed appropriately until your late teens and twenties. So those kinds of social media impacts on young people's minds at a time when their frontal cortex is developing is critical to their future brain health and potentially their risk of Alzheimer's. So yes, Alzheimer's is pivoting from just a problem of aging to a real life course challenge to maintaining and enhancing brain health

Meryl Comer (05:23):

On that point, brain health is influenced by culture, diet, lifestyle that varies across the globe. So how does the Brain health movement adapt its strategies to meet unique needs of different regions without imposing a one size fits all?

George Vradenburg (05:39):

As you know, the Davos Alzheimer's Collaborative is doing a lot of work in Africa, and Africa is the most diverse continent on the face of the earth, and by 2050 will be 40% of the world's population. So here we have a population in Africa where there's a big bowl of young people as well as a rapidly growing aging population. So as we look at Africa and its differential genetics, its biomarkers of aging and development, its social markers of social and brain resilience, they'll be different in Africa, and indeed they'll be different in the five different regions of Africa. So the need to understand how best to look at the populations of the world is going to be not only important, but critical to brain health.

Meryl Comer (06:23):

George, how do you see the brain health movement intersecting with the explosive growth in AI and the longevity movement?

George Vradenburg (06:31):

We are living longer, but our health is not increasing at the same rate and same pace as our lifespan. So healthy longevity is becoming a movement around the world, but healthy longevity is based upon many, many factors that occur during the course of your life and not just at the end of your life. Artificial intelligence is another fascinating set of developments. Depending on how you think artificial intelligence is going to develop, it either can be seen as an extension of the human brain and an extension of our own power to be creative and to think of problems. Much like when I was going into high school, I changed some slide rules to a little handheld calculator, right? So all of these little devices can potentially enable the human brain to focus on more creative things, more empathic things, a variety of social things and less on calculations and paperwork, and could be enormous extension of the human brain, or it could be our enemy because it's attempts to substitute for the human brain. So how this develops is vitally important, but I see artificial intelligence through an optimistic lens. I think it is going to be an extension of human capacity, human intelligence, and indeed our ability to increase the human productivity of the smaller workers in the workforce supporting larger populations may require us to use artificial intelligence techniques to enhance our own productivity in the workforce.

Meryl Comer (07:58):

George, the amyloid hypothesis continues to remain under debate by the critics. It also has challenged the issue of scientific integrity and quite frankly, just further confuses the public perception of Alzheimer's research. What opportunity or challenge does this present for advocacy organizations like UsAgainstAlzheimer's?

George Vradenburg (08:22):

Well, there's the challenge to make sure that people understand that in fact, the United States Congress ought to continue to invest in Alzheimer's research and that those investments are wisely made and productive to true medicines that improve the lives of people. So we have to understand where that scientific misconduct occurred, whether it is infected, the ongoing research of the space, and whether it's infected in any way, the drugs that have been developed in this space. And the answer to the latter question is absolutely not. I mean, sort of the gold standard of whether or not a amyloid hypothesis work is a clinical trial of an amyloid lowering drug, which actually demonstrates benefit in randomized clinical trials, which are approved, reviewed closely by the Food and Drug Administration. So the proof of the pudding here that this is not a hypothesis based upon some scientific misconduct, is the fact that we do have clinical trials of multiple drugs.

George Vradenburg (09:20):

Many of them have failed. But now we're beginning to see, as we hone in on precisely what it is in the amyloid protein that we need to hit, we're seeing drugs that actually work and it produce clinical benefit of importance to patients. Some will dismiss the clinical benefit of these drugs as modest and maybe even insubstantial. But if in fact, these drugs are demonstrating that in fact it delays the progression to moderate disease by up to two years, that additional time with families is vitally important to patients. And while you may poo poo, it is not a cure. Poo pooh it. It hasn't stopped the disease. That two year delay in progression to moderate disease is vitally important to patients. So we have to both look at the bottom line results of actually amyloid lowering drugs and how they work, and at the same time, make sure that people understand that whatever scientific misconduct has occurred and it has occurred, that we isolate it, understand it, condemn it, police for it going forward, but make sure that people understand that that was 10 and 15 years ago and the trials that were conducted that produced those false results couldn't be replicated so that that particular thesis was not pursued.

George Vradenburg (10:32):

So the scientific misconduct is cabined to where it should be in history, but hopefully continues to be policed, something that clearly is important to avoid.

Meryl Comer (10:42):

George, the National Institute of Health's bypass budget for fiscal 2025 calls for an additional 318 million in Alzheimer's research funding. How does that align with the NAPA goals for the development of prevention and effective treatments? 

George Vradenburg (11:01):

Every year, the National Institute of Aging estimates what additional funding it needs in order to advance to the goals which we had of a disease modifying drug by 2025, of which we now have too. But we now have extended the NAPA strategic plan process to 2035. So every year, NIA presents a professional judgment budget to Congress directly and says, this is how much more we need in order to continue to achieve progress in this space. And so Congress has been responsive to those professional judgment recommendations and have consistently increased year over year the amount of funding allocated to Alzheimer's research at NIA that will continue this year. Before the change in administration, one would've said that there was going to be an additional budget for Alzheimer's research in this fiscal year between 100 and $300 million, depending on when you're talking about the House or the Senate.

George Vradenburg (11:56):

But that whole thing has been hung up in what is called a continuing resolution, which means that everything is sort of frozen until Congress acts, and it has been frozen now for six months, and we will see where that comes out in this year. There is clearly a movement because of the change in administration and the <inaudible> sentiment that budgets are out of control. Our government annual deficit now being approximating a trillion and a half to 2 trillion, that there will have to be cost savings. And as a consequence, there's no question that the NIH budget as a whole and NIA budget for Alzheimer's is going to be under pressure. We can't predict what the budget is for 2025 or 2026 and beyond. It is a challenge because we're running such government deficits. There is a strong sentiment, and I think in both parties that we have to do something to cut back either on spending or increase in taxes or a combination of those two things right now, lot of things on the table, and we don't know where all of that is going to play out, but it will be very public and very messy.

Meryl Comer (12:57):

The current research initiative supported by the NIA emphasizes the importance of studying different geographic, racial, ethnic, and socioeconomic groups. Why is this ongoing focus on diversity and equity in Alzheimer's research critical regardless of the administration in power?

George Vradenburg (13:17):

Well, American population is approaching the 50 50 population of whites on the one hand, and so-called ma racial minorities, blacks, Latinos, native Americans, Asian Pacific Islanders in the aggregate. And one of the concerns that I think in the Alzheimer's community is that it appears as if some of the diagnostic tests that we have been using to sort people into clinical trials may not work the same way with the same effect in racially distinct populations. And we don't know exactly yet why. It could be because different racial populations have a different mix of pathologies of dementia, more mixes of vascular dementia than pure Alzheimer's dementia. Or it could be there's some slight genetic differences which produce dementia at the same level, but with different genetic factors, which is causing these diagnostic tests that have differential performance. So I think there's a real concern. Concern is probably not the right but definite interest in understanding why and how this disease may be operating differently in different populations. And that of course goes to recruitment to clinical trials and assuming clinical trials are representative, you want them representative so that in fact, you can study the differential impact of a particular medicine in different subgroups. And this is a real challenge going forward, and I think there's a lot of effort to try and make sure that we understand those differences. We understand how to make clinical trials representative, we understand the different diagnostic tests that can be used to make sure that we can detect this disease in different racial populations with equal effectiveness.

Meryl Comer (14:53):

George, as a businessman, do you feel there's a roadmap for advocacy that makes equity a business imperative rather than a regulatory requirement?

George Vradenburg (15:03):

Well, if I were a businessman and I had a medicine that I thought was going to be attractive to and benefit populations, I want to make sure that it gets to, I have my maximum market, so to speak, that I have proven that in fact therapy actually works in whites and blacks in Native Americans in Pacific Islanders effectively so that the population who has presented with these potential medicines has confidence that the medicine has been tested in people that look like me. Well, certainly from a patient advocate's point of view, we represent all patients, white, black, Latino, and men and women, which is another distinct subset of people that should be getting access to these medicines. So we as a patient advocate, want representative clinical trials. We want as much assurance as we can obtain economically that in fact, these drugs work for all subpopulations of the United States and that Medicare will cover these drugs for all populations in the United States.

Meryl Comer (16:00):

George, when I introduced you, I mentioned a number of multiple satellite organizations that you've spun off from us against Alzheimer's. Was that part of the innovation needed to address the complexity of trying to find a cure for Alzheimer's?

George Vradenburg (16:15):

This happened organically because we started us against Alzheimer's really as a political organization because Congress was not allocating very much money to Alzheimer's research. And indeed the common thinking at the time among the larger Alzheimer's associations, basically, you can't start a war. You can't try and ask Congress to ask for more money for Alzheimer's than for cancer or for other diseases. You're simply setting off a disease war. And you and I, as co-founders of this organization, didn't accept that premise. So we started as a political organization to try and get Congress's attention to the then large and increasingly growing numbers of people that are experiencing this disease and the families that suffer with them. So we started there, but as you look into this, and you started to say to yourself, as we did in those, some of those early convenings that we did back in 20 11, 20 12, what are the big problems confronting this disease?

George Vradenburg (17:07):

The second one, beyond funding was clinical trials. They were slow and they were sluggish, and they were difficult, they weren't representative. And hence, we spun off the global Alzheimer's Platform Foundation in 2016 in order to address that issue. Well, the next issue is how do patients talk to industry to understand what industry's problems are in innovating more rapidly and greater volume? So we created the global CEO initiative on Alzheimer's to bring together all the biopharmaceutical companies that indeed had an interest in the Alzheimer's indication. And now there are a number of biopharmaceutical companies there as well as diagnostic companies. And that particular corporate round table, we call it, is deeply involved in blood tests, understanding their qualifications, how to use them, how to get them more widely adopted in primary care, how to get digital cognitive assessments, new digital technologies into consumer's hands, as well as in clinician's hands.

Meryl Comer (18:01):

George, there's a growing segment of the population in both the US and globally that are anti-vaccine. Why does the CEOI have a work group focused on the challenge of developing an Alzheimer's active immunotherapy or vaccine in the next five to 10 years.

George Vradenburg (18:19):

We got called, as you know, fried Klaus Schwab of the World Economic Forum, who said he had incubated these large global mechanisms called Gavi and cepi and the Global Fund to Attack infectious diseases. And he basically said, you know, those are epidemics of an infection, and Alzheimer's is basically an epidemic of demography, but it's an equal kind of impact around the world of an infectious diseases having, so would you come work with me? And we accepted to try and bring in the global south and to understand this challenge at a global level. So this has evolved not with any particular rationale, but in response to the growing perception of the ever increasing impact of this set of diseases, these brain disorders around the world, and the increasing recognition that in fact, this is a life course disease and the recognition that this is not just a science matter.

Meryl Comer (19:12):

George, what are the projected global costs of Alzheimer's care if a preventative vaccine is not developed?

George Vradenburg (19:20):

Well, we have an estimate of 150 million families by 2050, and I think now they've just recently increased that estimate to 155 million at a cost today of a trillion, at 200 million a year doubling every 10 years. So we're looking at an annual cost to the world of eight to $10 trillion by 2050. And one of the things that persuaded our Congress to increase the investment in Alzheimer's research was the estimate that in fact, the cost of Medicare and Medicaid alone in the United States was going to equal the Defense Department budget by 20 42, 20 43. So just the cost of care for those with Alzheimer's globally is going to really potentially bankrupt some governments or simply they'll just have to put this back on their people and not provide any government assistance, which means huge amount of suffering, large losses in the workforce, and huge economic impact beyond the cost of care.

Meryl Comer (20:19):

What are the unique challenges when trying to ensure the global public health effort also protects middle and low income countries?

George Vradenburg (20:27):

I go to the World Health Summit every year, and all of the conversation all the time is about infectious disease and about vaccines. The rest of the world knows how to administer vaccines. And those vaccines have become not only safe and effective, but affordable. And the challenge is simply getting people to take those vaccines and to have people have access to those vaccines. The current crop of Alzheimer's drugs and the projected crop of Alzheimer's drugs absent a vaccine, means that most of the world is not going to get access to a medicine for Alzheimer's for decades. Decades. So the notion of trying to drive to a vaccine is an effort to try and get a low cost accessible means of treatment to people around the world. It's a critical effort, and the initial clinical trials have been positive. The vaccines seem to work, and they seem not to have any safety issues, but the large clinical trials that you need in order to demonstrate this with confidence, they're only now beginning. We'll start seeing results from those really in the next couple of years. And if in fact, they are as safe and effective as we think they may be, we will head our target of having something on market by 2030.

Meryl Comer (21:38):

You've been listening to George Vradenburg, Chairman and Founder of UsAgainstAlzheimer's, whom as you've heard used his business acumen and personal philanthropy to seed a nimble and collaborative advocacy organization that today connects globally and a quest to promote brain health and prevent Alzheimer's disease.

George Vradenburg (21:58):

Now, will people take a drug when they're seemingly healthy on the hope that in fact, it will prevent their progression to full-blown dementia by four or five years? We don't know the answer to that. If we make it simple enough, I think there's a significant percentage of the population that is sufficiently fearful of this disease, particularly if they've had it in their family, or particularly if they have genetic risk, that they'll take it.

Meryl Comer (22:22):

That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.

Closing (22:28):

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