Alzheimer’s risk is shaped by genetics, environment, and lifestyle, according to emerging research. Dr. Sid O’Bryant’s groundbreaking Health & Aging Brain Study – Health Disparities (HABS-HD) is paving the way for specialized treatments tailored to diverse communities.
Growing evidence shows that Alzheimer’s risk is shaped not only by genetics but also by culture, environment, and lifestyle — and researchers say these differences may hold the key to better prevention and treatment.
Dr. Sid O’Bryant, professor of pharmacology and neuroscience at the University of North Texas, is the principal investigator of the Health & Aging Brain Study – Health Disparities (HABS-HD), the most comprehensive Alzheimer’s study ever conducted across African American, Hispanic, and non-Hispanic white communities. His approach brings research into diverse communities often left out of large-scale studies, ensuring that findings reflect the populations most at risk.
In this conversation with Being Patient’s Mark Niu, O’Bryant explained how factors like diabetes, hypertension, environment, and even social support networks shape brain health. He explained that these findings show why Alzheimer’s cannot be treated with a “one size fits all” model. Instead, precision medicine — tailoring prevention and treatment strategies to an individual’s genetic, cultural, and lifestyle background — could transform how we approach brain health and Alzheimer’s treatments.
Being Patient: The Health and Aging Brain Study (HABS-HD) is the most comprehensive Alzheimer’s study across diverse populations. First, tell me, how does this study work? What tests do you perform?
Dr. Sid O’Bryant: We have enrolled over 5,000 people, and it’s extremely robust. We do interviews, testing of memory and thinking, blood work, clinical labs, a brain scan for an MRI, as well as two more brain scans for looking at specific things associated with Alzheimer’s disease. People come in every 24 months, and they normally spend about four visits with us.
We give back so much to our community and our participants. One of the things that I love so much about it is the data is actually freely available to the global scientific community. So it’s out there to help people.
Being Patient: Tell me about the various races you’re studying.
O’Bryant: We’ve enrolled over 1,600 Hispanic Americans, 1,600 Black Americans, and 1,600 non-Hispanic white Americans.
We enroll in both English and Spanish. We don’t yet have the capacity to do assessments in other languages. One thing that’s important to note is we actually do not exclude based on race or ethnicity. Anyone can come into the study age 30 and above. We’re trying to make it very representative and reflective, since we’re in Texas, of the Texas population.Texas is already where the United States will [be] in the next 20 years, so we’re trying to [represent] what the United States looks like. We want brain health for everybody.
Being Patient: What makes this study different from past large-scale Alzheimer’s research efforts?
O’Bryant: In the Alzheimer’s space and brain aging in general, often the recruitment is done at specialty clinics, and those are normally accessible only to well-educated white individuals or people with means.
What’s unique about this study is we don’t recruit from clinics. We go to the community. Our study, in the last five years, has provided more brain scan data than any study in history.
That’s not a limitation to the field, per se. It’s more that people didn’t get out into the communities. They thought they understood what Alzheimer’s looks like. What we said was, okay, now we’re taking the next step, and we’re going to get out there and see how we can meet everyone’s brain health needs.
Being Patient: What are some of the most striking differences you’ve uncovered so far between African American, Hispanic, and non-Hispanic white participants in terms of Alzheimer’s risk factors?
O’Bryant: Most studies have not enrolled people with uncontrolled diabetes. We don’t really care what someone’s diabetes is in order to come into the study. We have such a range that now we’re finding diabetes has a very strong impact on brain health, and we’re seeing that impact more among the Hispanic community, which is not surprising given the increased risk for diabetes. The important thing is we can do something about diabetes. There are ways to intervene. That’s a huge entry point in the future for prevention.
Same thing with vascular issues in the brain, like uncontrolled hypertension. We’re finding those vascular issues [are] more common among the Black community and more strongly associated with brain aging.
We’re finding that some of these medical comorbidities that we already know impact communities differently are also differentially impacting brain health over time, which means we can [intervene] — but we need to be careful who we’re doing what with. That’s where precision medicine comes in.
Being Patient: When you’re looking at diabetes, as one example, are some of those factors more genetic or more from social determinants?
O’Bryant:First of all, what I want everyone to realize is that Alzheimer’s is not just some genetic disease where if you have some gene, you’re going to have Alzheimer’s — with very rare exceptions. But there’s this genetic risk factor called APOE4, which increases risk for Alzheimer’s disease. What we’ve now learned is that there’s genetics and then there’s ancestry. Where we come from matters. Now we’re looking at it and [saying] that APOE4 risk is important for people coming from this area of the globe, historically, but not this area of the globe. Even genetics are modified by social context over time.
On top of that, the environment you live in impacts how your genes function. So it’s complicated. I don’t think one can pull it apart and say there are certain things that are just genetically related in terms of causal factors. Brain aging and Alzheimer’s are more complicated than that. There are sociocultural constructs, like our normal diet. I grew up in the South, in south Louisiana, [we ate] gumbo, soft pecan, étouffée — not great for diabetes and heart disease. That absolutely increases the risk. We have to think in terms of how the environment, the social, and the biology come together.
“Even genetics are modified by social context over time.”
Being Patient: Are there other things outside of diet that you’re seeing?
O’Bryant: Recently, one of the studies came out and showed that lifestyle interventions are capable of slowing or changing the profile and risk over time. We have some data looking at physical functioning. Even someone’s physical functioning right now, like a Timed Up and Go [test] — how fast you get up to walk in 60 seconds — we’re finding that is related to the biology of Alzheimer’s disease itself.
One of the other things we’ve done, and others have as well, is use this thing called the Area Deprivation Index, which is this measure of the environment you live in. What we can show is that those communities themselves and those geographic areas may also have different risks, which could be due to quality of education, living in an area with high traffic, or different environmental conditions.
Being Patient: How is your study advancing biomarker research?
O’Bryant: I’ve spent my entire professional career working on building blood tests to increase access to care. We’ve had a big impact there because we want representation. Our people look like the community. Now people are getting access to our blood samples, running their studies, and realizing they need to look at other things in order to better interpret results.
Even mild kidney disease, for example, impacts blood levels. With brain scans, the big thing is the ATN BrainNet Framework. We’ve shown that amyloid plaques, tau tangles, and even neurodegeneration are differentially associated with outcomes. We’ve probably impacted the biomarker space more than anything at this point.
Being Patient: I thought I had read in one of your findings that the levels were lower in Hispanics in at least some pilot research in some areas.
O’Bryant: People say a brain is a brain is a brain. No, it’s not. You’ll hear in the news about amyloids. Amyloid is a plaque, a protein in the brain that sticks together and over time kills the brain cells. That’s all amyloid is. But amyloid is a key thing for the biology of Alzheimer’s disease — a defining characteristic.
We have now found that if we take, say, 100 Hispanic, 100 Black, and 100 non-Hispanic white participants — all with memory loss that looks like Alzheimer’s disease — the non-Hispanic whites are going to have much higher values of amyloid in their brain than the Blacks and the Hispanics. So even though clinically it may look like Alzheimer’s, the underlying biology is different.
Being Patient: Is there any difference with tau tangles in the different groups?
O’Bryant: Tau is a tangle — another protein that gets dysfunctional and kills the brain cells. Tau is what people think of as causing memory loss, not amyloid. You have amyloid, and then once tau is there, memory goes down. What our data is now saying is not necessarily.
When amyloid is there and tau is there among non-Hispanic whites, yes, that is consistent with other findings. What we’re seeing is that when amyloid is there among the Hispanic community, it’s neurodegeneration — brain shrinkage associated with diabetes. That tau link looks different, even among Blacks.
Another cool thing that we’ve found is tau is related to diabetes. If tau is driving memory loss, if we can find the subgroup of people where it’s diabetes doing it, you now have a multimodal therapy.
Being Patient: What are those precision treatments? Because we don’t have so many treatments right now for Alzheimer’s. What would be an example of precision medicine?
O’Bryant: The entire point of HABS-HD is to get us to precision medicine. I want to help doctors treat your [individual] Alzheimer’s, your brain loss. That’s how cancer is treated. They treat your specific tumor. It’s not about whether it’s breast cancer versus prostate cancer — it’s about what the tumor looks like. That’s where Alzheimer’s needs to be, and I think that’s where we’re headed.
Saying someone has amyloid in their brain isn’t precision medicine, in my opinion. Of those with amyloid, there is a subgroup where amyloid is aggressive. In that subgroup, amyloid rapidly changes memory. Get them on a therapy and pull it out of their brain. There’s another group where it’s amyloid plus depression, or amyloid plus diabetes, or something else.
A lot of people say Alzheimer’s is too complicated, there’s so much going on. What I tell people all the time is that’s the key to beating it — the complexity itself. I was the kid who loved pulling apart everything. I wanted to see the pieces. If we say your brain aging and memory loss is associated with depression, that’s where we’re headed.
“A lot of people say Alzheimer’s is too complicated, there’s so much going on. What I tell people all the time is that’s the key to beating it — the complexity itself.”
Being Patient: You’ve already shared a couple of fascinating findings, but are there any others that really surprised you?
O’Bryant: Yeah. There’s a group of early career scientists down in Austin. One of them is a rising superstar. She created this way of looking at our data that’s just amazing. She looked at the community within which someone lives — high stress, low stress. Then she created this resiliency [measure] of social support.
She found that in the presence of high stress and low social support, the biology of the disease looks different. But in a high stress area with resources, the biology looked like those in a low stress area. If you live in a high stress area but have a support system, ways to cope, and a positive outlook, it actually changes the biology of the disease. That was one of those moments when I looked at the data and thought, wow, that’s cool — and inspiring.
Being Patient: What’s next for your Health and Aging Brain Study? I think there are some other studies you’re involved in too, but what are some of the key areas you’re hoping to connect the dots?
O’Bryant: The next big space for this study that I’m hoping to move into — it always depends on funding — is movement issues, [such as] Parkinson’s. Alzheimer’s disease is related to Parkinson’s and Lewy body [dementia], but all of the Alzheimer’s studies exclude movement disorders, and movement disorder [studies] exclude Alzheimer’s. We have those brain scans associated with Lewy body and Parkinson’s that no one has ever looked at among these represented communities. That is a huge area that we’ve got a whole working group on. Precision medicine not just for memory loss but for movement disorders as well. Once you start combining those things, we’ll get even closer to precision medicine.
Being Patient: Anything else you’d like to wrap up with here that offers advice for people?
O’Bryant: What I want everyone to understand is: own your brain health. This is not outside of your control. I’ve already said things you can do. You can work on physical activity to help protect your brain. You can work on keeping diabetes and hypertension under control. You can work on your mental outlook on life.
Own it. Take control of it. Don’t sit as a passenger in a car. Grab the wheel and steer your own brain into a healthy life as you age. If I could leave everyone with one thing, it’s this: Don’t be afraid — be empowered.