Article In Brief
MRI showed that people who were of White and Latinx backgrounds had different levels of white matter hyperintensity and cortical thickness than those who identified as Black.
Black people are more likely to show earlier signs of brain aging compared with White or Latino persons, according to an analysis of nearly 1,500 brain scans from two community-based studies examining factors of aging and Alzheimer disease (AD).
Researchers used MRI to look at two measures of cerebrovascular disease and neurodegeneration—white matter hyperintensity (WMH) and cortical thickness—and found differences among people of different racial and ethnic backgrounds.
“In this study, racial and ethnic disparities in small vessel cerebrovascular disease were apparent in midlife,” the researchers reported Nov. 14 in JAMA Neurology. “In Latinx and White adults, brain aging was more pronounced in late life than midlife, whereas Black adults showed accelerated patterns of brain aging beginning in midlife.”
The new study did not provide any definitive explanation for potential causes underlying the racial and ethnic disparities in brain aging, but it suggested that “the cumulative impact of social, physical, and economic adversities,” including racism, may account for why Black people seem to age more quickly.
“Different groups of people have different lived experiences, and we have to understand what those experiences are and how they contribute to brain aging,” said the study’s senior author, Adam M. Brickman, PhD, a professor of neuropsychology at Columbia University. He said the study results should not be interpreted to suggest genetic or biologic differences result in the disparities in brain aging, but rather that life circumstances may result in the brain aging sooner, on average, in Black people.
“I think the labels of race and ethnicity capture a number of social factors that go hand in hand. You can list institutional racism, structural racism, personal racism, economic and educational opportunities, access to health care, etc.,” Dr. Brickman said.
Background information in the current study describes what researchers call “the weathering hypothesis,” which suggests that “repeated exposure to stress, suboptimal environments, and social disadvantage contributes to wear and tear on the body, leading to a faster rate of aging in Black and Latinx people.”
The paper noted that while previous research found racial and ethnic differences in brain health in later life, not much is known about what occurs at middle age.
Community Participants
The new study included participants from two diverse New York City-based studies that enrolled older and middle-aged adults: the Washington-Heights-Inwood Columbia Aging Project (WHICAP) and the Offspring Study of Racial and Ethnic Disparities in Alzheimer Disease (known as the Offspring study).
The WHICAP participants were residents of northern Manhattan, aged 65 or older, and fluent in England and/or Spanish. They were recruited in three waves, beginning in 1992, 1999, and 2009. The current analysis included people from the 2009 cohort who received brain scans with 3-T MRI beginning in 2011.
Participants in the Offspring study were adult children of WHICAP participants who were 25 or older and fluent in English and/or Spanish. The current analysis included Offspring participants enrolled through January 2021 who received MRI scans.
All participants were asked to self-report their race and ethnicity as Black, African American, or African and non-Latinx (all categorized as Black in the analysis); Hispanic or Latino, Latina, or Latinx of any race (categorized as Latinx in the study); or White and non-Latinx (categorized as White).
Participants underwent an MRI and also had their medical history taken for diabetes, hypertension, heart disease, and clinical stroke. Neuropsychological tests evaluated cognition; none of the participants had dementia when scanning was conducted.
The final sample included 1,467 people, 497 from Offspring and 970 from WHICAP. The mean age in the Offspring group was 55, and participants had 13 years of education on average. The group comprised 23.5 percent Black adults, 70 percent Latinx adults, and about 6 percent White adults. WHICAP participants had a mean age of 75 and 12 years of education on average. The group was comprised of nearly 35 percent Black adults, 40 percent Latinx adults, and 25 percent White adults.
MRIs were analyzed for cortical thickness, a standard biomarker for neurodegeneration in AD-related regions of the brain, and WMH volume, a marker for small vessel disease that is associated with risk of stroke, cognitive decline, and AD.
The researchers found no differences in cortical thickness in midlife among people of different racial or ethnic backgrounds but did observe that Black participants had greater WMH volume in midlife, suggesting that their brains aged sooner than their White or Latinx counterparts. In late life, Blacks fared worse than Whites or Latinx by both measures of brain health.
“In middle-aged White and Latinx participants, the relationship between age and WMH was relatively weak but then got much stronger in late life,” Dr. Brickman said. “But in African American participants, the relationship between age and WMH was already strong in middle age, similar to what it was in late life.”
“We concluded that there is accelerated brain aging (on average) among African Americans beginning in middle age,” said Dr. Brickman, who noted traditional cardiovascular risk factors, such as hypertension and diabetes, don’t explain the disparities found in the study.
First author Indira Turney, PhD, an associate research scientist at Columbia, said it is well documented that people who identify as Black or Hispanic are two to three times more likely, respectively, to be more at risk for AD, but it isn’t fully understood why these disparities in brain health exist. She said the Columbia research team plans to explore the relationship between brain aging and social determinants of brain health using participants from the same community-based cohorts.
The researchers plan to assess “a series of life course factors including wealth, discrimination, neighborhood segregation, etc. to determine the various structural racism-related factors that may influence brain aging,” Dr. Turney said. “At the end of the day, the goal is to reduce brain health disparities by developing interventions that address these differences and also understand the factors that contribute to brain equity.”
Evolving Methodologies
Some scientists say caution is needed when drawing conclusions about social determinants of health because research methodologies related to understanding it are still evolving. Neuroimaging may show differences in brain aging, for example, when comparing race and ethnicity at a group level, but it is not clear how to interpret the findings, said Rhoda Au, PhD, professor of anatomy and neurobiology, neurology, and epidemiology at Boston University Chobanian & Avedisian School of Medicine and the School of Public Health.
Researchers have begun to recognize the importance of social determinants of health, but it is a complex issue that has not been adequately studied, Dr. Au said.
“I think we need to be very careful about oversimplifying the factors that account for these differences,” she said. “We tend to do that in research—we use reductionistic approaches that make things more easily understandable to ourselves. I’ve been advocating for embracing the full complexity of the problem; instead of fitting our science into the methods we know, we need to develop new methods that actually fit the science.”
Dr. Au, one of the principal investigators of the Framingham Heart Study Brain Aging Program, said that project has shown the pitfalls of oversimplifying the findings, such as saying a particular food is good or bad for the heart. While findings at a group level can be useful for tailoring community- and population-based interventions, Dr. Au contends that the future of dementia and AD prevention and treatment lies in the same personalized “precision medicine” approach used increasingly in cancer care.
Beau M. Ances, MD, PhD, FAAN, Daniel J. Brennan MD Professor of Neurology at Washington University in St. Louis, said the two community-based cohorts used for the Columbia brain aging study are among the better-designed community-based brain health studies.
“A unique aspect of the [current] study is that they looked at brain aging at midlife and later life, finding a different rate of decline,” he said, with the downward slope starting sooner for Black people. “It is a really good paper,” he said, but noted that one limitation was that it only provided a look at neurodegeneration of the A/T/N (amyloid, tau, and neurodegeneration) framework used in AD research, so the full perspective on the brain status of participants was not complete.
Dr. Ances, who conducts research with some members of the Columbia team on the relationship between Down syndrome and AD, has used a community-based study of memory and aging ongoing at his center to also look at potential racial and social factors in brain aging using the A/T/N measures. The study, published in Annals of Neurology in 2021, found that area-level socioeconomic status may contribute to observed racial differences in the degree of neurodegeneration.
He said the new findings from Columbia will help “set the stage for further research” into “not just the biology but also the environment or the lived experiences” that influence brain health.
“In middle-aged White and Latinx participants, the relationship between age and WMH was relatively weak but then got much stronger in late life. But in African American participants, the relationship between age and WMH was already strong in middle age, similar to what it was in late life.”—DR. ADAM M. BRICKMAN
“I think where science is going is that it isn’t an either/or scenario, assessing medical factors versus social or environmental factors. What influences brain health is multifactorial and may differ for different groups.”—DR. ROBERT W. TURNER II
“You just can’t look at individuals and not look at the context in which they live. What we don’t know yet is if there is a sensitive period or a critical period [that especially influences brain aging].”—DR. ANDREA WEINSTEIN
Andrea Weinstein, PhD, a clinical neuropsychologist and assistant professor of psychiatry at University of Pittsburgh, said the most important finding of the Columbia study is that brain aging seems to begin by middle age on average for Black people, which could help better tailor and time intervention projects. Often, brain-health programs are targeted at older people, but “you don’t want to wait until it’s too late,” she said.
Dr. Weinstein, a researcher with a study called Think PHRESH that is based in two Pittsburgh neighborhoods, studies the relationship between physical and mental health and neighborhood factors such as housing value and safety. (One of the Columbia researchers, Jennifer Manley, PhD, also is involved in the project.)
“You just can’t look at individuals and not look at the context in which they live,” Dr. Weinstein said. “What we don’t know yet is if there is a sensitive period or a critical period” that especially influences brain aging.
While societal factors, such as racism or the condition of a neighborhood, are hard to prove in a cause-and-effect manner, “in the US, you can’t rule out that White people and Black people are having different cumulative experiences,” Dr. Weinstein said.
Robert W. Turner II, assistant professor in the department of clinical research and leadership at George Washington University School of Medicine & Health Science, agreed that the science of social determinants of health currently relies on quite basic and incomplete tools that are likely to be refined over time, but he said the new study from Columbia is a step toward “helping us to get at the root causes, the pathology” of racial and ethnic health disparities.
Dr. Turner, who studies concussion in football players using social determinants of health as well as traditional measures of injury and recovery, said he is interested in the concept of accumulated stress when it comes to brain health and that what happens upstream may influence outcomes downstream.
“At the end of the day, the goal is to reduce brain health disparities by developing interventions that address these differences and also understand the factors that contribute to brain equity.”—DR. INDIRA TURNEY
“I think we need to be very careful about oversimplifying the factors that account for these differences. We tend to do that in research—we use reductionistic approaches that make things more easily understandable to ourselves. I’ve been advocating for embracing the full complexity of the problem; instead of fitting our science into the methods we know, we need to develop new methods that actually fit the science.”—DR. RHODA AU
“I think where science is going is that it isn’t an either/or scenario, assessing medical factors versus social or environmental factors,” Dr. Turner said. “What influences brain health is multifactorial and may differ for different groups.”
Disclosures
Dr. Brickman reported personal fees from Cognition Therapeutics for scientific consulting and serving on the scientific advisory board of CogState outside the submitted work and had a patent issued for technologies for WMH intensity quantification. He also received fees from Regeneron. Drs. Turner, Weinstein, and Ances had no disclosures.
