Decoding Dementia: What You Need to Know

Evan Banks

You're listening to Policy Minded, a podcast from RAND. I'm Evan Banks. Today we're joined by Peter Hudomiet and Jodi Liu, RAND experts who recently conducted a series of studies looking at ways to improve screening and treatment for Alzheimer's disease and other dementias. Peter is an economist, and Jodi is a policy researcher. Welcome, Peter and Jodi.

Peter Hudomiet

Thanks for having us.

Jodi Liu

Happy to be here.

Evan Banks

Let's start by talking a little bit about the medical conditions that you are looking at in this research, Alzheimer's disease and related dementias. Alzheimer's affects almost 7 million Americans and there's no cure. And even more people in the U.S., more than 12 million, are estimated to have mild cognitive impairment, which could be a sign of Alzheimer's or other illnesses. Could you give us a broad overview of the symptoms and conditions you are aiming to learn more about with this research?

Peter Hudomiet

Alzheimer's disease is the most common form of dementia taking up about two-thirds of all cases. But there are other dementia forms, as well. The most common is vascular dementia, which typically occurs after a stroke or other cardiovascular problems. And there are other types, as well. So, we're going to talk about four studies today. We looked at different things, but most studies looked at all-cause dementia. So, we did not differentiate between the subtypes, but sometimes we only focused on Alzheimer's disease, the most common form. And you mentioned mild cognitive impairment, that also came up in our research. Mild cognitive impairment usually means a state when people already developed some cognitive problems. We think that they are on the pathway to dementia, but they are not there yet. And of course, it's very important to identify people when they are in that state.

Jodi Liu

And I think it's important just to remember that dementia is—it's a slow-moving condition. It's a progressive neurodegenerative disease. And we looked at this sort of life course from normal cognition to some cognitive impairment to dementia, and we focused on different aspects across these different studies.

Evan Banks

Okay. Peter, you're an economist. Before we get into the findings, I'm curious, how does an economist approach the examination of a topic like this?

Peter Hudomiet

Are you asking that how do I dare studying a health topic as an economist? So, I'm a health economist. I'm primarily interested in the well-being of the older population, and that includes their financial well-being like retirement, pension, health care costs, but also other things like their health. And I've been working on dementia-related topics for over ten years now. Recently, for example, I had a study on trying to find job characteristics that predict dementia later on, and we had some interesting findings there. And then this research that we're going to talk about today, we looked at like more broadly about like other risk factors of dementia. But in general, how do economists do it? Well, we do it with good data. And economists love analyzing data. They love applying fancy statistics to the data. And, and we're pretty good at that. Now what we are not necessarily trained on is understanding the clinical implication of our statistical findings, and for that we have like other researchers with medical backgrounds who help us out.

So, here at RAND we tend to work in multidisciplinary teams and that's tremendously useful for a person like me who is mostly like a data geek. So, measuring dementia is actually not as easy as you might think. For example, many administrative data sets, such as data sets from the Medicare, they only have doctor-diagnosed dementia. But many people who have dementia actually don't get diagnosed because they don't interact with the healthcare system often enough. So, in those data sets we are worried about underdiagnosed and even misdiagnosed dementia. And in surveys—we use survey measures of dimension in our study— it's actually not so easy to measure that, as well. You can't just ask people that, hey, do you have dementia? Again, many people don't know about that, that they have it. And even bigger problem is that many people who have it, they cannot answer survey questions. So, they will just not participate in your survey. And if you want to reliably study these questions, then you have to account for these problems, and we did. So, we worked very hard to kind of fix these problems.

Evan Banks

Let's get into the research. We're going to be talking about multiple studies today. Taken together, they provide insights into risk factors for Alzheimer's and related dementias, screening for cognitive impairment and early detection treatment, and more. Can you outline the high-level questions you were trying to answer with this research?

Peter Hudomiet

So, the first study looked at risk factors for dementia and primarily focusing on early detection of dementia up to twenty years before the symptoms arrive. And for that we looked at both modifiable risk vectors of dementia, such as your behaviors, exercising, drinking, and so on, but also looked at other risk vectors that are harder to modify, like your education level and so on. In the second study, we looked at how people who already have an assessment for cognitive problems, what they can do. So, some actions that they could take to improve their well-being.

Jodi Liu

And the next two studies were really focused on the clinical care side. So, the next one looked at first what patients—what affects patients' decisions to go in to get a cognitive screening test, to go in for diagnosis, to go in for treatment. And then the last study looked at how the provider side, so how do healthcare providers and the amount of healthcare providers meet that patient demand and how do—what does it look like in terms of supply and demand to deliver the services needed.

Evan Banks

Let's rewind a little bit and talk about the risk factors. What were some of the strongest risk factors you identified that predicted who would be more likely to develop dementia?

Peter Hudomiet

The strongest risk factor, not surprisingly, was people's cognitive abilities at baseline. So, people who performed better on various cognitive tests at the age of 60, they were much less likely to have dementia 20 years later. And this may not be all that surprising, but maybe it's worth talking about it, why it might be the case. Economists like approach this question from the point of view of human capital theory. So, the idea is that as people invest into their human capital, their brain functions, once the brain function starts depreciating as you get older, you still have that human capital to maintain your function. In medical science they use a very similar theory, but they call it the cognitive reserve theory. And it's pretty much the same idea. So, people who have cognitive reserve, once their brain starts going through some neural degradation and they start losing these connections in their brain, they still have more connections. And that helped them to maintain function and they can take care of themselves. They don't need to rely on other people.

Evan Banks

Beyond cognitive ability, are there any other risk factors worth mentioning?

Peter Hudomiet

Yes, so in this study, we looked at 181 risk factors and we found many strongly predictive ones. Some of them were not that surprising and a few of them were quite surprising, at least to me. Among the non-surprising ones, the strongest one was basically good physical health. So, if you maintain a good physical health when you're middle-aged, you're much less likely to develop cognitive problems later on. And that included survey questions about please rate your health from full to excellent, but also things like exercising. People who never exercised, they had a much higher chance of having dementia later on. And actually, those who exercised a lot, that seemed to matter not as much. So basically, the big difference was between those who never exercised or exercised a little. We also found that severe obesity at midlife strongly predicted dementia later on. And already having a stroke or having diabetes were also very predictive of dementia later on.

And now let me talk about the more surprising ones. One of them was that people who were born in the southeastern part of the U.S., they were much more likely to have dementia later on. And that was true even when we controlled for a whole host of factors, for example, their health. And it still remained predictive, which I found fascinating. We also found that people who have private health insurance when they are 60, they were less likely to have dementia later on. And we don't fully understand why that is. But nevertheless, this is what we found. And we also found that those who never worked had a substantially higher chance of developing dementia. Working more also mattered, but the main difference was between those who never worked versus worked a little.

Evan Banks

One of the lifestyle factors that you looked into that really surprised me was never drinking alcohol or drinking excessively, which you would maybe expect or associated with cognitive impairment and dementia. But I was surprised that never drinking alcohol was associated with cognitive impairment.

Peter Hudomiet

Yes, so this is what everyone finds the most interesting result, and everyone always asks me about that. So yes, this also surprised me a little bit, and it's worth mentioning it here that we used observational statistical methods in this study. So, these are not randomized controlled trials, so we cannot really establish causality. We can find statistical associations that maybe future research can verify or not. However, this finding that excess alcohol consumption is bad for you is not surprising. Not drinking at all alcohol might look surprising, but if you go back a few decades, medical—the doctors tended to recommend people a little bit of alcohol a day, like one glass of wine may be good for you. Now, this recommendation more recently got dropped. And again, I'm only an economist. I'm not a medical scientist, but my understanding is that the main reason for that was because they found out that alcohol increases cancer risk and even a moderate amount of alcohol consumption increases cancer risk. But at the same time, a little bit of alcohol might still be good for your cardiovascular health.

So, when we're seeing this result, that a little bit of alcohol might be good for your cognitive health or later on, it might be because cognitive health is related to those cardiovascular health. So, overall, I would still not tell you, recommend you to start drinking alcohol. If you don't drink alcohol, don't start it. But probably a moderate amount of alcohol consumption is also not that bad for you. So, you don't need to be worried about it that much if you are worried about your cognitive health.

Jodi Liu

Peter, can I ask, is it also true that there might be some relationship with social aspects for people who are never drinking? Is it maybe a proxy for having social interactions with others?

Peter Hudomiet

That can very well be the case. And yes, it could be that people are more lonely, also never drink alcohol, and that's a signal of you being, get out, social interactions, yes.

Evan Banks

But I do want to add, not a medical recommendation. Jodi, you mentioned loneliness. Was that one of the risk factors you identified? And how do you measure loneliness?

Peter Hudomiet

So, we actually looked at loneliness and we did not find a strong association there. There are multiple ways of doing that, by the way. So, you could just ask people to rate how lonely they feel. That one was a little bit predictive. We also looked at, for example, how many people live in people's households. And there we found very little action again. But for example, if people are completely alone, so they are widowed, for example, or never married, again, we saw some some association there. So, there were some, but these were not among the strongest risk factors. The health-related risk factors were much more predictive of dementia than these social ones.

Jodi Liu

I think having hobbies though, maybe it was one that was perhaps more predictive.

Peter Hudomiet

Yes, we also looked at whether people engaged in cognitive tasks, for example, whether they play chess. And again, we found, again, the finding was that those people who just never engaged in such hobby activities, those were very predictive of dementia later on. And those who engaged in some of them, at least a little, they were already doing pretty well.

Evan Banks

Let's move to talking about screening and detection. I mentioned early detection at the top of this episode. Can you talk about how important it is and what kind of difference it can make for someone who may be diagnosed with Alzheimer's disease?

Peter Hudomiet

So, as we just discussed, there are modifiable risk factors of dementia and if you have an early detection of some cognitive problems, well, here you go, now you know that you should modify those risk factors. So, if you already are not exercising, if you are not eating healthy, then now is time to change that and hopefully you can at least delay the onset of Alzheimer's disease. But there are actually other factors, too. People, for example, can prepare for the inevitable. And one important aspect could be getting help with finances. For example, asking your children to help with your financial decisions and start involving them in your financial decisions so that they understand your preferences. But also, it may be a good idea to to have a will. And because now is the time to make good decisions on that. Now you're more capable of doing that that you will be in a few years. And also, it is time to think about the care arrangements that you want to do in the future. You need to get plans for that. So, do you want to move in with your children? Do you want to move in with other relatives? Or do you want to go to a nursing home? And if so, then how? How will you finance that? It's very expensive in the United States. So overall, I think delaying the onset and preparing for the inevitable.

Jodi Liu

Then on the clinical side, and we have these new therapies, these disease-modifying therapies, these are therapies that only work at the early stages of Alzheimer's disease. So, once someone has progressed to moderate or severe dementia, they're not eligible for these treatments, and also, it's thought that there's no way to really reverse that damage. So, in order to get the benefit from these types of therapies, you would need to intervene and get treatment at a really early stage. That early detection is key to identifying who can benefit from these treatments.

Evan Banks

What does this screening process look like right now, and what do we know about how many people are getting screened?

Jodi Liu

So, people will go and get screened for different reasons. I think the most common is someone might have a memory complaint, maybe they have a family member or a friend who has noticed them forgetting things and having some memory issues, so they might go in and ask their doctor about that. A cognitive assessment can be done by a primary care physician; it could be done by a nurse or even a trained social worker. So, for people on Medicare, there is an annual wellness visit that is supposed to have this check for cognitive impairment. But there's no standard way that it's done and it doesn't often get done. Surveys have found that maybe 15, maybe up to 30% of people actually get this cognitive assessment. People on Medicare Advantage might have a little bit higher rates than that.

Evan Banks

Why aren't people getting these assessments? Is it because they don't know to ask for them or you have surveyed results that have insight into this, right?

Jodi Liu

Yeah, so I think it's a combination of factors. The reality is a wellness visit is maybe 30, 40 minutes, and there's a lot of different issues people at these older ages will want to talk about. There's not a standard recommendation for one tool that's always used, so it can look pretty different. And it kind of depends on how much time is available from that provider at that visit, and how much is available from the healthcare system to pay for those visits. And, um, I think about whether to come and do it at that visit or to come in for another visit to talk about that. Then I think there's still a lot of hesitancy to talk cognitive issues. It's a sensitive topic for the patient and for the provider, too. There's been studies that have looked at the level of trust needed between the patient and provider and some thoughts on the provider side about whether to engage in the conversation at what point when there may not be something to do right away. So, I think that there's a lot we can do still to normalize the conversations in talking about brain health so that people can proactively start planning.

Peter Hudomiet

We also ran a survey, and we directly asked people what they think about that but what they think the main reason is to not get these cognitive assessments. And one of the top reasons that came out was the cost of it. So, people were much more likely to want those tests if they are free or at least they are moderately expensive. People also said that they were worried about confidentiality. So, they were worried that if they have like a positive result that they are at higher risk for Alzheimer's disease then maybe their health insurance would go up or their long-term care insurance would go up. So, they were worried about that. And people also mentioned that they were worried about how they will be treated by others at work or even at home. Maybe they will take away their freedoms and they were worried about that. These were the top reasons.

Evan Banks

Can these screenings be done by primary care providers as opposed to neurologists or specialists? And can you talk a little bit more about why that's important?

Jodi Liu

So, these cognitive assessments can be done by primary care providers. There's many different validated, standardized tests that can be used. Some of them are as few as two or three minutes. There are versions that are 10 to 15 minutes. And then there's a longer battery of neuropsychological testing that can be done for up to an hour or multiple hours. And so, it kind of depends on what type of cognitive assessment is done. The initial screen usually will be a shorter assessment. And that can be done by the primary care provider and can be a physician, it could also be a nurse. There are different programs that have trained social workers to do these assessments. The key part I think is familiarity with these tools and training. There's also digital cognitive assessments that are becoming more common. So, I think a lot of it is about engaging the primary-care practitioners to do it themselves, to do team-based care, because really there, the primary providers are the kind of entry point for a lot of people to start this process in talking about their cognitive health with the provider.

Evan Banks

On a personal note, my grandfather actually passed away from Alzheimer's and I remember he was brought to live with us when I was a little kid. And by the time that happened, he was already in the advanced stages of cognitive impairment. I do wish that if there was a screening around, then I don't know that he knew that it was possible to do that. So, I think it would have—it definitely would have been preferable for me and my family and my experience that that be identified earlier. It's just, it's a difficult thing to want to know, I guess, but also it does help the people that you love prepare, so.

Jodi Liu

Absolutely. It is a difficult thing to want to know, and I would say that, and this has been changing a lot over time and some things take time to change in terms of those perspectives. There are still perspectives out there that this is a normal part of aging. There's nothing that can be done. And so, this isn't necessarily something you think about intervening, even though there are things like you can do like the modifiable risk factors that Peter talked about, like some of these new therapies. And so, it's really important to engage people—individuals, families—in it, but also providers, right? Providers are people, too, and they also need to have familiarity and understand how there are new tools available. At the same time, you know, I think it's really important to engage primary care providers, but they're also being asked to do a lot already, and there's a lot of challenges in asking them to do even more. So, it's so important that the engagement really comes with making it as easy as possible for them to integrate it into their routine care, make sure that it's easy for them to do it, make sure they're familiar with the tools, and it's clear what kind of standardized tools they can use.

Evan Banks

Well, let's talk about some of those new therapies. We've talked about risk factors, screening, and detection. So, let's about treatment. What is the current treatment landscape for Alzheimer's disease and related dementias? There's no cure, but what options do people have and how well do they work?

Jodi Liu

Right, so there is no cure. There have been treatments out for many years to manage severe symptoms of dementia. What's changed a lot in the last few years is the availability of these disease-modifying treatments. So again, these are treatments that are for people at very early stages, and it slows the progression of the disease. So, it slows down the cognitive decline so you can stay in an earlier stage then progressing to a more advanced stage of dementia. So, there's been technically three therapies approved since about mid-2021. And they're pretty modest in terms of how well they work. They tend to keep people in an earlier stage of dementia for maybe two to eight months longer on average. And there's some more studies recently showing that people can live independently longer if they're on these therapies. But there's also risks. There are severe side effects for a small number of people on these therapies that involve brain swelling and brain bleeding. And if you have a certain type of two copies of the same gene, for example, like, you are at more risk. If people who have had a stroke or have been on blood thinners are also at more risk for that. So, there are a lot of benefits and risks to consider when thinking about going on these therapy.

Evan Banks

Do people who are diagnosed often receive these kinds of treatment, and if not, why not?

Jodi Liu

So, let me first say that diagnosis is not a quick and easy thing. Diagnosis takes time. It's multiple visits. It usually involves lab testing and imaging to rule out other causes of dementia. These therapies are for Alzheimer's disease and not for other dementias. So, usually when you're starting to assess this, you don't know what is the cause of the dementia. And so, then there's visits to do what's called biomarker testing to confirm that you actually have the Alzheimer's disease pathology. So, you have what is dementia caused by Alzheimer's disease. And then there also needs to be checks to see what's—there also need to be checks to see how severe the dementia is. Once your people are at a moderate or severe stage of dementia, then they're no longer eligible for these treatments since they're not thought to be effective.

Once people are diagnosed, you know, it's been changing over time. They're still relatively new. There was a lot of controversy over the first therapy that was approved. And all of them now have pretty modest effectiveness, and there has been a lot of concerns about those side effects. The side effects also require regular monitoring, so people need to go in at regular intervals to get checked, so it's not just you get a pill and take it home, and these are infusions, intravenous infusions. You go in once a month or once every two weeks and get an infusion, and then you have to go back to get MRIs on a regular basis. So, it does require quite a lot of time to get on these therapies and stay on them. And then there's also the cost. These are pretty expensive therapies.

Evan Banks

Speaking of costs and receiving treatment, one of your studies looked at the geographic variation in the U.S. of accessing these treatments. Peter, you mentioned the Southeast U.S. in particular. What did you learn about differences in treatment availability and wait times based on where someone lives?

Jodi Liu

So, the studies we did looking at the wait times really focused on not just the treatment itself, but the diagnosis. We've found that the kind of what causes the wait times really is getting that diagnosis, which requires time, and it typically now is done by a specialist, so a neurologist or a geriatric psychiatrist. And so, because there are relatively few specialists and in certain areas, like rural areas, there tend to be fewer specialists, that's where a lot of the wait times that we found occurred, and we found that in rural areas, on average, people waited about three times longer than in urban areas. Many studies have shown that dementia is underdiagnosed in certain groups. For example, racial and ethnic minorities tend to have lower rates of diagnosis for a variety of reasons, and that all contributes to having lower access to both the therapies that are available and also to any sort of advanced planning and different things you can do in advance of having more severe dementia.

Evan Banks

How about forthcoming treatments, so, treatments that aren't out yet, but may be on the way? Some have already been given FDA approval. Some are still in the clinical trials, and that's good. Given these sorts of wait times and barriers to treatment that we just talked about, what might happen when these new therapies become widely available? And will people be able to get them if they need them?

Jodi Liu

I hope that they will, and it depends a little bit on what these therapies look like. I think the barriers we talked about, just people going in for early detection, having those conversations with their providers, the process of getting the diagnosis and determining treatment eligibility, those all are things that can still be barriers that requires people and their families to have time to go through those steps. It requires providers to be engaged and deliver those types of services. And so, all of those things will still be barriers, and having also the provider payment that's adequate for the providers to do these diagnostic services is really important and the cost, of course, on the part of the patient's family matters, too.

Evan Banks

We covered a lot of ground today, but before we close out, what's the most important takeaway from this research?

Peter Hudomiet

Well, for example, that you should stay healthy and if you want to delay the onset of the disease then you should stay healthy. Also, do cognitive assessments early on so that you know what's ahead of you. And I think another one is that we need better drugs. So, the drugs that we currently have, they are just not not good enough and, and in our surveys, actually, people said that one reason, another reason they didn't want to do these cognitive assessments, because it's not worth it. There are no effective treatments. So, we need more research on that.

Jodi Liu

Yeah, and I would say we need to do all of these things and there are multiple points within all of this that we can work on to make outcomes better for people who have cognitive impairment and dementia.

Evan Banks

Peter and Jodi, thanks for joining us today.

Peter Hudomiet

Thank you.

Jodi Liu

Thank you.

Evan Banks

You can find more information about the research we discussed in today's show at rand.org/policyminded. Thanks for listening. And thanks again to our guests, Peter Hudomiet and Jodi Liu. This episode was produced by Deanna Lee and was recorded by me, Evan Banks, and Emily Ashenfelter. Emily also edited today's episode. RAND's Director of Digital Outreach is Pete Wilmoth. We'll see you next time on Policy Minded. RAND is a nonprofit institution that helps improve policy and decisionmaking through research and analysis.