In six massive laboratory freezers at the University of Utah, nearly 40,000 blood samples wait in frozen stasis.
They represent four years of data from one of the largest studies of hypertension in the U.S.: an intensive blood pressure intervention study called the SPRINT trial. And hidden in many of these blood samples are subtle chemical signals that point to their donors’ current and future brain health conditions-among them Alzheimer’s disease and related dementias, the most common cause of disability among adults over 65.
Now, powered by a $21.6M, five-year National Institutes of Health grant, researchers are poised to unlock this informational treasure trove and uncover the connections between hypertension, Alzheimer’s disease, and dementia.
Linking blood pressure to brain health
High blood pressure is one of the biggest modifiable risk factors for dementia-progressive problems with memory and thinking that interfere with daily life. The most common kind of dementia is Alzheimer’s disease, caused by protein buildup in the brain, but dementia can also be caused by problems with the blood vessels in the brain. It’s unknown exactly how high blood pressure harms the brain, or how blood pressure management strategies might help.
The project will analyze the vault of blood samples for molecules that specifically herald either Alzheimer’s disease or other forms of cognitive decline. The project is funded by the National Institute on Aging, a division of the National Institutes of Health. Adam Bress, PharmD, professor of population health sciences at University of Utah Health, investigator at the VA Salt Lake City Healthcare System, and a principal investigator on the study, explains that the project aims to answer a few big questions:
- “How does lowering blood pressure more intensively affect brain health?
- Does [hypertension treatment] affect brain health through pathways around Alzheimer’s disease-protein plaques and tangles-or is it through the blood vessels themselves?
- How does having Alzheimer’s pathology in your brain impact how we treat your high blood pressure?”
New technology to find new connections
Key to answering these questions will be the researchers’ use of a new technology: a recently discovered blood biomarker that diagnoses Alzheimer’s-related brain changes nearly as well as the gold standards of a brain PET scan or cerebrospinal fluid sample.
The blood biomarkers will be cross-referenced with comprehensive health information to determine how the effectiveness of blood pressure treatment can change based on genetics, demographics, and existing health conditions. For instance, the study aims to find out whether intensive hypertension treatments still reduce dementia risk for people with genetic susceptibilities to dementia. Answering these questions will help doctors provide targeted interventions to help each patient.
Rachel Hess, MD, associate vice president for research at U of U Health, emphasizes the value of the unique U of U-based biobank that makes this study possible. “The University of Utah is proud to be the home for the SPRINT biospecimens, which are a legacy of all of the SPRINT participants and researchers across the country,” Hess says. “This biobank lets us query samples that could be over a decade old and answer new questions with new biomarkers to gain novel insights into how hypertension control can change the course of aging for millions of Americans.”
Helping patients and driving science forward
We hope that the results of the study will help people by contributing to our understanding of how and in whom hypertension confers the highest risk for dementia, guiding more individualized treatment for hypertension, and ultimately lowering dementia risk in those individuals using medicines for blood pressure.”
Jeremy Pruzin, MD, behavioral neurologist at Banner Alzheimer’s Institute in Phoenix and a principal investigator on the funded study
Bress adds, “The other thing that’s crucial about this grant, which is probably one of the biggest things, is we’re going to post all the data publicly.” Data on five different blood biomarkers will be matched with clinical cognitive outcomes and dementia diagnoses-a detailed resource to power future studies. “This is going to be one of the largest repositories of its kind in the world.”
Jasmeer Chhatwal, MD, PhD, behavioral neurologist at Mass General Brigham and Harvard Medical School and a principal investigator on the study, says, “The advent of blood-based biomarkers for neurodegenerative disease will change the landscape for screening, diagnosis, and treating cognitive impairments in older adults. The results from this study will be crucial to understanding how we might implement these new tools in a ‘real world’ population.”
“This innovative research uses novel-blood based biomarkers and clinical trial data to decode dementia pathology and, in doing so, will provide answers about how blood pressure affects brain health and how we can best treat people living with both Alzheimer’s Disease and hypertension. Ultimately, this work can help protect people’s memory, independence, and well-being,” says Angela Fagerlin, PhD, chair of population health sciences at U of U Health.
This work will be funded by the National Institute on Aging of the National Institutes of Health (grant number 1R01AG096179-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
This project was made possible by a strategic investment from the office of the associate vice president for research, the Departments of Population Health Sciences and Internal Medicine at University of Utah Health, and the Utah Diabetes and Metabolism Research Center (UDMRC) office. Other researchers who contributed to the success of the grant include Angela Fagerlin, Scott Summers, John Inadomi, Rachel Hess, Alfred Cheung, Tom Greene, and Yizhe Xu.
Source:
University of Utah Health