Thursday, March 6, 2025
Dr. Sid O'Bryant is the principal investigator of the Health & Aging Brain Study – Health Disparities (HABS-HD), which is the most comprehensive study of Alzheimer’s disease among the three largest racial/ethnic groups in the U.S. ever conducted – African Americans, Hispanics, non-Hispanic whites.
Research on Alzheimer’s disease biomarkers is often limited by the lack of diversity in study participants, resulting in a significant gap in understanding how the disease progresses across different racial and ethnic groups. Studies have shown that all-cause dementia is most prevalent among Black and Hispanic individuals, yet these groups make up only about five percent of all clinical trial participants.
Dr. Sid O’Bryant is principal investigator of the Health and Aging Brain Study-Health Disparities project (HABS-HD) at The University of North Texas Health Science Center at Fort Worth. HABS-HD is ongoing, with more than 5,000 people enrolled and given two-year follow-ups.
“HABS-HD is the most comprehensive ongoing study of brain aging among representative communities in U.S. history,” O’Bryant said. “The study is designed to understand the earliest signs of brain disease with the ultimate goal of the generation of a precision medicine model for treating and preventing Alzheimer’s disease.”
O’Bryant recently spoke at the Human Amyloid Imaging conference, held Jan. 15-17 in San Juan, Puerto Rico where he discussed in his keynote address how disparities in dementia research arise from recruitment challenges and unequal access to health care. However, he highlighted that emerging data is revealing biological differences in how dementia develops across various populations.
Finding limitations
UNTHSC is a research site for the AHEAD Study, two clinical trials testing investigational treatment in people with risk for memory problems. A recent analysis of screening and recruitment data from the ongoing AHEAD clinical secondary prevention trial revealed that Black individuals were less likely to have brain amyloid, a protein that can lead to memory problems due to Alzheimer’s disease, compared to non-Hispanic white individuals, which led to their exclusion from the trial.
O’Bryant explained that these findings challenge scientists’ broader understanding of the causes and characteristics of Alzheimer’s disease and related dementias.
Most of the data used to design the amyloid, tau and neurodegeneration biomarkers in the recently created ATN research classification framework came from the Alzheimer’s Disease Neuroimaging Study, which features more than 90 percent white participants, and the Mayo Clinic Study of Aging, which began in 2004 in Minnesota’s Olmstead County and is 97 percent white. The ATN Framework is a research framework explicitly designed as a biological conceptualization of Alzheimer’s disease with the intent of advancing clinical trials.
“As was highlighted in many talks at HAI 2025, the ATN framework, as demonstrated by HABS-HD data, varies between racial/ethnic groups,” O’Bryant said.
HABS-HD study breakthrough
O’Bryant’s HABS-HD study has the statistical power to begin examining disease progression in diverse populations.
“Several studies have now shown that brain amyloid (i.e., plaques) is different among Hispanic and Black individuals as compared to non-Hispanic whites,” said O’Bryant. “Our data also shows that tau (i.e., tangles) is also different. Therefore, HABS-HD clearly demonstrates that representation in brain aging research is extremely important to have a comprehensive picture of the complexity of the disease.”
“HABS-HD is designed specifically to understand the disease progression and to determine how different biological, environmental, medical and social factors impact progression,” O’Bryant added. “By understanding these things, we can progress to true precision medicine for Alzheimer’s disease.”
Recognition for the HABS-HD study
During a presentation at the HAI conference, Dr. Annie Cohen from the University of Pittsburgh School of Medicine discussed one of the initial efforts to quantify these differences on a broad scale, using data from the HABS-HD cohort. Her team analyzed data from MRIs, tau and amyloid PET scans from 1,082 non-Hispanic white participants, 1,079 Mexican American participants and 605 non-Hispanic Black participants from the HABS-HD study, all of whom had varying degrees of cognitive impairment.
The researchers analyzed the patterns of amyloid, tau and neurodegeneration in each group. For white participants in the HABS-HD cohort, the patterns of disease followed the ATN framework. In contrast, in both the Black and Hispanic groups, all three pathologies were detectable simultaneously and progressed at roughly the same rate. Meanwhile, in the white group, the three pathologies progressed at different rates. Among subgroups of Black individuals, the sequence of these biomarkers also varied.
Dr. Reisa Sperling, who co-directs the Harvard Aging Brain Study, finds the Texas HABS-HD data compelling in showing that amyloid cannot be the only target when studying diverse populations with dementia.
Cohen told Alzforum, a news website dedicated to Alzheimer’s disease and related disorders, that multiple processes contribute to cognitive decline.
Future trials, she said, should study combinations of factors across diverse populations, such as the Alzheimer Plasma Extension observational study which studies biomarkers in people who did not qualify for the AHEAD trial. More than half of those in the study belong to racial minority groups.
At the HAI conference, Dr. Lindsey Kuchenbecker and Dr. Minerva Carrasquillo from the Mayo Clinic analyzed plasma biomarkers in the Florida Consortium of African American Alzheimer’s Disease Studies. Their goal was to identify proteins related to immune response or vascular disease, particularly in non-white populations. Carrasquillo emphasized the need for more research on diverse risk factors in these groups. Kuchenbecker noted that while disease-related brain proteins may not appear in plasma, the predictive power of these markers suggests they can distinguish Alzheimer’s disease from controls. The team is now investigating these markers in other diverse cohorts.
These findings outline that late-onset dementia may be influenced by different biological factors and causes based on a person’s racial and ethnic background. To effectively prevent dementia, it’s important to understand the social factors that contribute to these differences.
As we begin studying individuals who have historically been excluded from research for various reasons, it’s important to be more cautious when interpreting how effectively the ATN framework will apply.
“I’m thrilled to see the field taking on these challenges,” O’Bryant said. “The ATN Framework, and trials that have resulted, was built on data that is not reflective of our community. The scientific field now realizes that where you come from matters. By having the data to point to these differences, we are now truly on the path for precision medicine.”
From HSC Newsroom - Research by Cindy Vasquez