What Population Research Can Tell Us about Alzheimer’s Disease Risk

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Show Notes

You can read about Dr. Rachel Whitmer's research work at the Whitmer Lab website. Her Current Studies page describes the studies she discussed during the podcast interview.

Dr. Whitmer also mentioned the MIND diet for healthy brain aging, created by Dr. Martha Clare Morris. You can learn about the MIND diet in the Dementia Matters episode featuring Dr. Morris.

Transcript

Intro: Welcome to Dementia Matters, a podcast, presented by the Wisconsin Alzheimer's Disease Research Center. Our podcast is here to educate you on the latest research, caregiver strategies, and available resources for fighting back against Alzheimer's disease. I'm your host, Nathaniel Chin. Thanks for joining us.

Dr. Nathaniel Chin: Today's guest on Dementia Matters is Dr. Rachel Whitmer, a professor and chief of epidemiology at the University of California-Davis and the associate director at the UC-Davis Alzheimer's Disease Center. Dr Whitmer studies population science to understand brain health and identify ways people can lower risk for dementia. Dr Whitmer, welcome to Dementia Matters, and thank you for being here.

Dr. Rachel Whitmer: Thank you so much for having me. It's really great to be here.

Chin: You're an epidemiologist. For our listeners who might not know what that is, can you explain what is epidemiology and how you use it to study dementia and Alzheimer's disease risk?

Whitmer: That's a great question because often in epidemiology, people sometimes assume that someone is studying skin. They think of the epidermis. So no, I'm not a skin doctor. Although certainly someone could do epidemiologic work on skin disease. One of the things that's a big trigger is people think of the word "epidemic," and then they think epidemiology. So when you think of an epidemic that's a outbreak, so that's a sudden increase in a disease. The nice thing about epidemiology is that it is not set up to only study infectious disease, it's also set up to study chronic disease. And so our lab is really interested in cognitive aging, brain aging, brain health, dementia and Alzheimer's disease. And so epidemiology is really a toolbox where you take a population-based approach. So you're looking at changes in a population of risk factors or protective factors, which are things that could lower risk. And you're looking at the number of people who are getting a certain disease or a certain condition. And so often you will look at new cases over a certain time period or you might, at a time period, just look at current number of existing cases, which is what we would call prevalence. So it's really taking a population-based approach to understand what might drive a certain disease.

Chin: Scientists and doctors are talking about modifiable risk factors for Alzheimer's disease. These are characteristics of a person's health or lifestyle or even details about their life that could potentially change. So for instance, for our listeners, a person's weight can change or a person can take blood pressure medication. And what are some of the modifiable or protective risk factors that you're studying?

Whitmer: Yeah, so we like to focus a lot on what we call modifiable risk factors. And what we mean by modifiable is first off, we like to look at things that happened really retrospectively. So we don't always like to look at things that are happening late in life, but we like to look at things early in life. So young adulthood or midlife or even in childhood. It sounds somewhat trite, but the adage what's good for your heart is good for your brain really does hold true. And you know, I hate to overuse a certain expression, but it really sums it up. If you look at the bulk of the work, it really shows that the things that you think about that you can do to help your heart and be heart healthy really also help the brain. So I can dig in a bit more. So there's a lot of work coming from our lab but has also been seen really around the world in multiple other studies is in midlife it's really important to have good vascular risk factors. So what do I mean by saying good vascular risk factors? Sounds sort of like a oxymoron, but you know, having good blood pressure; if one does have hypertension, having adequate control. Trying to avoid diabetes or if you have diabetes having really good glycemic control and following your targets. Having a healthy weight in midlife. We've also looked at smoking. So of course, you know, it might sound quite obvious that of course smoking is bad for the heart. Why wouldn't it be bad for the brain? But a really interesting thing was there were studies at one point that were case control studies where you take a group of older people with Alzheimer's and a group without, and those studies seem to suggest that smoking was good for you, that it would actually lower risk of Alzheimer's disease. There were also some studies done where they were following older people just over a short time period. And this is one of those sorts of interesting epidemiologic choice where you can imagine if you're a heavy smoker and you didn't succumb, you know, first of all you live to age 70 or 80. You didn't get a stroke, you didn't get a heart attack. You're very unique, and that is what we call sort of selective survival. So of course you're also at lower risk of Alzheimer's disease. But this is where Epi really comes in, that it's also important to follow people over time. So we published actually the first and kind of the longest followup looking at pack years and heavy smoking and found that it was a very robust risk factor. Of course, it sounds quite obvious now, but at the time it was the first paper, you know, showing that heavy smoking does elevate risk of dementia and Alzheimer's disease. It makes sense; it's linked with stroke -- that has been also replicated several times. We've also looked at high cholesterol. And then we've also been very recently in the last few years focusing on what we call sort of social epidemiologic questions. We're very interested in racial ethnic differences in rates of aging and how much of that can be explained by differences in some of these psychosocial exposures. We've been looking at not only years of education but also looking at state of birth. We've published some work looking at if you were born in a state that has a very high stroke mortality risk or a state that at the time had exceedingly high infant mortality rates, you are subsequently at higher risk of dementia. And these studies were all done with our cohort from northern California. So these people were all living in northern California by their sixties and seventies. Yet simply being born in one of these states significantly elevated risk, and it seemed to play a really big role for our African American community. A lot of them had come from the South. We're now doing some follow-up studies and really trying to dig into what was the educational system like for these people. What was the access to healthcare. So trying to really understand, you know, early life exposures to adversity or social deprivation, how does that set up your brain sort of long-term for risk for dementia.

Chin: So not only are you working to understand this very complicated disease, but in essence your findings could affect public policy and how do we take care of our citizens? How do we take care of people knowing that these factors happen from the state in which you were born?

Whitmer: Yeah, absolutely. And we are doing some, you know, follow-up studies where we're really gonna dig in and look at, you know, segregation, number of days that schools were open, you know, really digging into that educational component because we know that that sets up the brain for either elevated or lower risk of accelerated brain aging. But absolutely these things have big implications for policy and really speak to the fact that if we did have really great access to good medical care and equal access to high quality education, it's not just about improving the quality of life, you are actually protecting your brain. It's actually linked to better brain health.

Chin: Now you're involved in many fascinating research projects, including as you've mentioned, the racial and ethnic differences in the development of Alzheimer's disease and healthy aging in African Americans. Now we don't have time to cover all of your research in our podcast, but I encourage our listeners to visit your lab website and read more about your work. Now we'll include the link to your website in our show notes for the episode, which will be posted on our website. But one study I did want to discuss is the POINTER study, for which you are one of the leading investigators. Could you tell us about that?

Whitmer: Sure. Yes. We are the second site for US POINTER. US POINTER is funded by the Alzheimer's Association. It is a lifestyle intervention study. So we've been talking today about epidemiology and about observational studies. And thank you for bringing up my website. I do have three really awesome studies, CANDLE, Life after 90, and Star, that you can read about. But this is not an epidemiologic observational cohort study. This is a lifestyle intervention. So this is a clinical trial where people will be enrolled in one of two interventions. One is a very structured intervention, which includes four days a week of physical activity. It also includes subscribing to the MIND diet, which is a combination of the Mediterranean and the DASH Diet, by Professor Martha Clare Morris, who's at Rush. It also includes some cognitive brain training games, social support, and more clinical oversight of one's risk factors. And so someone could have any number of risk factors. The other group is a self-guided intervention, which will be health education materials about how to make one's lifestyle better, and clinical oversight as well of risk factors. But none of the other things, no adhering to a diet, no cognitive brain training, and no physical activity. This trial is modeled after the FINGER trial. So the FINGER trial was done in Finland by Professor Miia Kivipelto. It ended a few years ago, and it was a lifestyle intervention study set up the same way, and found a positive association between lifestyle changes and less cognitive decline. What's fascinating about FINGER and US POINTER is that we really haven't in the U.S. had a large scale, multiple domain, multiple behavior changes, lifestyle intervention trial yet. We've had some really exciting smaller trials. We've had trials that have focused on one thing like physical activity, but no one has done something that's looked at all these different things. So as I said, I am the PI at UC Davis along with Doctor Sarah Farias. We are site number two. Site number one is Wake Forest. They are also the coordinating center. And Rush to site number three and we'll be announcing sites four and five soon. The study will enroll 2,000 people, so 400 at each site, 200 in each arm. And these are elderly people who cannot be a super physically active. So they have to be a bit sedentary, and they can't, for example, already be following the MIND diet. So, they have to have somewhat of an of an unhealthy lifestyle, which unfortunately isn't hard to find in the U.S. just because the way our infrastructure is set up -- folks sometimes have trouble getting access to healthy food and finding time to exercise. What's so exciting about this is that, you know, the FINGER trial was successful. It was done in Finland, which is a very different place than the U.S. But we are all part of this World Wide FINGERS, which is a network, and really an infrastructure, funded by the Alzheimer's Association to encourage sites around the world to try to emulate the FINGER study. So we have SINGER in Singapore, there's going to be Canadian in Canada, there's MIND-CHINA in China. So it's quite exciting. And of course, none of these places can deliver the exact prescription that was delivered in Finland. So for example, the diet that they did in Finland, would that make sense in Singapore or China? No, it wouldn't. So it's really the same recipe, but kind of different ingredients. So what's so wonderful about it is when you're doing lifestyle interventions, you have to think about what makes sense in that culture, in that country, in that socio cultural context.

Chin: And how long will the study be?

Whitmer: It is a two-year followup. It is a five-year study. We're assuming it will take about a year and a half to enroll people once they're enrolled. They're seen every six months, over two years. And the primary end point is cognitive change. So looking at, do those people in one group versus the other have a different pattern of cognitive change over the followup.

Chin: And speaking of one group versus the other, more and more research is showing that Alzheimer's affects different groups of people differently. From your work, what do you find when it comes to modifiable risk factors and protective risk factors and the different groups of people that you study?

Whitmer: Yeah. So we do see disparities. We do see differences by certain racial ethnic groups in just rates of dementia. And we're really seeking to uncover why, and we really approach race as a psycho social construct. And we do see huge differences and just exposures to things. We see huge differences in who was born in the U.S. We have certain racial ethnic groups where over half of them were not born in the U.S. We see enormous differences in access to education. We see really large differences in the level of education of the parents. So there was all these really big differences in sort of what happened earlier in the life course over these groups. So I think it's really important when we're looking at differences in just the epidemiology of dementia or Alzheimer's disease. You know, it's important to quantify what those differences are. But the next question is why?

Chin: For people who are interested in learning more about what you're doing, they can go to your website. And again, we'll have that on our podcast and on our website. And for people who are interested in the mind diet that you talked about, Dr. Martha Clare Morris to an interview with us earlier last year. And so that episode is also available earlier in our series. And again, thank you for being on our podcast, and the next time you are in town we'll ask you to join again.

Whitmer: Thank you. Thank you for having me.

Outro: Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health, and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private, university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's disease centers. This episode was produced by Rebecca Wasieleski and edited by Bashir Aden. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.