Studying Alzheimer’s from a Sociocultural Perspective: UNTHSC-TCOM’s NIH Grant Breaks Brain Biology Barriers

Sid O’Bryant, PhD, executive director of the Institute for Translational Research at HSC, TCOM professor

Frank Filipetto, DO, Everett Endowed Professor, TCOM dean

The answers below have been edited for brevity and clarity.

Q: Dr. O’Bryant, how did you become interested in studying Alzheimer’s and other neurodegenerative diseases?

Dr. O’Bryant: This is a personal journey for me. I grew up in south Louisiana in a very open household, but a very divided environment. Even as a child, I knew the health disparities I was seeing were inappropriate. Later, in the middle of my neuropsychologist training at a VA in Albany, New York, I saw a lot of patients being referred for memory loss. This was pre-Gulf War, and these patients had to wait a long time to see a specialist or get a diagnosis. At the same time, I got a call from my parents in Louisiana who told me that my grandmother (pictured left) was having health issues. After working with my family to get therapeutics initiated for my grandmother, I saw how difficult and incredibly expensive it was just to get a diagnosis. I remember the day I walked into my family's house, visiting, and my grandmother looked at me and started crying. I was the grandbaby, the youngest grandchild. I was very close to my grandmother, and she knew that she knew me, but she didn't know who I was. From that point on, I decided that this was going to be my life's journey. Anyone who walks into my office sees her picture. I display it and keep it near me as a reminder of why I do this work. Many of the people who have joined this team have also experienced either Alzheimer's, Parkinson’s or some other neurodegenerative condition in their family, so this research is very personal for me and my team.

Q: Dr. Filipetto, as the largest grant the University of North Texas System has received, what does this funding mean for the institution?

Dr. Filipetto: This is a transformational opportunity. This grant is going to change the trajectory of Alzheimer's research, but more importantly, it will address health disparities. It will link the two together. This project gives us a great opportunity to change the way we look at Alzheimer's disease and, really, change the world.

Q: Dr. O’Bryant, how did you hear about this grant opportunity and what motivated you to apply for funding?

Dr. O’Bryant: This project began when I moved to TCOM in 2012, so we've been doing this work for a decade now. Before this grant, we received $60 million in NIH funding for the cohort. The new funding is an expansion and continuation of that project. We’ve been publishing Mexican American brain aging research for a very long time, and I've personally been doing health disparities work since 1996. Through this new project, we can continue to demonstrate that race, ethnicity, culture and where you grow up are very important factors to consider in brain aging. To date, there has never been a large-scale comprehensive study of the biology of Alzheimer's disease across diverse communities within a health disparities framework. Oftentimes, the biological studies do not consider sociocultural factors and don't include diverse communities, while the sociocultural, environmental studies that incorporate underserved communities don’t cover the biology. We have done a lot of both. This equipped us to approach the NIH about our capacity to build the most robust, comprehensive study ever conducted anywhere on the planet in a community that already reflects the demographics of where the United States will be in the next 20-30 years. I spent almost a year negotiating with the National Institute on Aging, because any study that’s more than $500,000/year in direct costs requires permission from the NIH to even apply, and the whole process took almost 24 months. It took some time because of our scope and size, we have 17 participating institutions, but now we can spend the next 20-30-40 years really understanding the life course of how the brain ages among diverse communities.

Q: Dr. Filipetto, how does TCOM support students who are interested in academic medicine and medical research?

Dr. Filipetto: A large majority of TCOM students participate in some form of research during their time here. We're fortunate to have several graduate schools as well as our medical school, and our students have access to excellent faculty researchers. Students can spend a summer or their entire four years doing research across specific specialties. For example, our Departments of Pediatrics, Geriatrics, Family Medicine and OMM all have research projects. We do our best to match students with their interests and with faculty here on campus, as well as with our adjunct faculty in the community. Students can also participate in dual degree programs. We have a dual degree PhD program, and recently created a research micro credential, which is a more sophisticated opportunity to conduct and present research both locally and nationally. Students can declare that on their CVs or in their portfolios, and it makes them more competitive when they seek residency opportunities. We're very proud of our faculty, and a grant like the one Dr. O’Bryant just received expands the ability for him and his team to further collaborate with our students.

Q: Dr. O’Bryant, how will you investigate the social and cultural factors that may be contributing to Alzheimer’s disease and why is it so important to research this from a sociocultural perspective?

Dr. O’Bryant: For the longest time there has been this general assumption that a wall exists between the central and peripheral nervous systems, that what happens in the brain is independent of what happens in the rest of the body and that the exterior is not related to the interior. Our research pushes back on these general assumptions. Our work, as well as that from others, has shown that environmental and sociocultural factors play a role in Alzheimer's disease. For example, we’ve used the area deprivation index, which is based on U.S. census data and is an aggregate measure of where one lives and one’s access to resources, to help demonstrate how living in a high-deprivation area relates to cognition. In this project, we will look at life-course residential history in both the U.S. and Mexico to expand on this work.  We also study perceived racism, social support, discrimination and whether participants have health insurance, a primary care provider and access to medical resources. When you think about it, if you don't have insurance, you have less access to medical care, so your medical comorbidities are probably uncontrolled, and we know that uncontrolled diabetes is horrible for your brain. That’s just one line that can be very clearly drawn to cognitive functioning and may explain why we see people who clinically present with Alzheimer's disease, but don’t have the expected biomarkers. This causes a dilemma where people who are experiencing memory loss, language issues and a decline in executive functioning, but who don’t have amyloid in their brains, aren’t being classified as having Alzheimer's disease. We’re seeing cognitive loss at younger ages and these sociocultural factors may be the underlying cause. We know that policy interventions can help address this, and we’re sharing data with some of the world’s largest pharmaceutical companies designing trials targeting underserved communities, so our approach is very broad-based.

Q: AACOM is actively working to  increase NIH osteopathic representation and research. What advice would you share with other colleges of osteopathic medicine that are interested in pursuing NIH funding?

Dr. O’Bryant: That's a great question. I know that colleges of osteopathic medicine are underrepresented in NIH portfolios, and I don't understand why. From my experience at TCOM, this is an amazing medical school with fantastic educators, clinicians and scientists. My first suggestion is to identify where you’re unique. What can you do to answer an important health question that isn’t currently being addressed? The second step is to find collaborators with existing infrastructure and funding. Team science is the name of the game. It’s the way you help patients, by working as a team to tackle big problems. Our Alzheimer's project is one of the largest in history. We have 17 institutions collaborating with us because we can't do everything alone. My third piece of advice is to lay the groundwork. You don't want to ask the NIH if you can build a cohort. You want to ask the NIH if you can expand and continue your cohort. It comes down to feasibility. You may have a wonderful idea, but the grant reviewer wants to know if you can pull it off. If you want to recruit 500 people from underserved communities, but you have no history of doing so, I’d question whether you can, because I know how hard that is. Fourth, be patient. Go after what's important and don't chase funding. You want to find the right teams and the right topics because at the end of the day, it's about helping patients. It's about strategic alignment of plans and vision, and persevering. Remember, the people with the most funding have the most rejections. If any schools ever need advice or assistance,  email me and I'll help you out.

Dr. Filipetto: I’d offer three suggestions, and these are all methods that Dr. O’Bryant employed and are similar to the strategies he shared. First, identify, focus on and invest strategically in a particular strength that you or your school have. Make sure this area is innovative and aligned with NIH priorities. Second, build a foundational framework and infrastructure. You’ll need institutional support to do that, and this will help you demonstrate to the NIH that you’re competent, committed and able to deliver. This may include developing cohorts of patients or data that you can share with the NIH to show them that you have a strong start and are ready to scale up. Third, learn to collaborate with groups and institutions that have NIH funding. If you can work collaboratively with successful institutions or colleges and share resources with each other, you’ll all rise to the top.

Q: AACOM recently launched a  critically important program dedicated to supplementing instruction around health equity and health disparities. Why is health equity so important from both an education and research perspective?

Dr. O’Bryant: I think this is the single most important topic that is being ignored. I love what AACOM is doing because if you don’t understand where your patient comes from, you can’t help them. Health inequities are the responsibility of the medical and scientific community. I feel very strongly that health disparities and health inequities are our fault. It's our job to deal with them. It's not the community's job to figure it out. Teaching this to the next generation of healthcare professionals is of tremendous importance. Historically, health professions students graduate with excellent training in medicine, but have never been taught anything about how sociocultural factors impact how a patient presents. I remember this one doctor we worked with who I just adored, he is a brilliant doctor, whose first line of prescription was Namenda, one of the more expensive Alzheimer's drugs. One of our participants came to me and said, “Dr. O’Bryant, I got a Namenda prescription, but I can’t afford it.” So, I called the doctor and we talked, and he didn’t realize the cost was so high. He’d been using this drug without knowing there were much more affordable alternatives. He was embarrassed and immediately fixed it. Understanding and being aware of these issues will make you a better and more empathetic health professional who has better relationships with patients.

Dr. Filipetto: Here at TCOM, we see health disparities in our communities. We have them in our own backyard, and as medical educators, we need to do a better job at not only explaining that to our students, but also empowering them with tools they need to address those disparities. We need to help our osteopathic medical students become innovative enough so that when they become healthcare leaders, they're able to fix the system. Social determinants of health have to be addressed, and that’s why we’re committed to teaching our students how to innovate and solve problems.