Article Archive
July/August 2018

Fighting Racial Health Disparities in Alzheimer's Disease: How Biology and the Social Environment Put Blacks at Risk for Alzheimer's Disease
By Ian McDonough, PhD
Today's Geriatric Medicine
Vol. 11 No. 4 P. 10

In 1932, the US Public Health Service conducted a study, now known as the infamous Tuskegee Syphilis Study, to investigate the natural progression of an infection caused by the bacterium Treponema pallidum. About 600 black men living in Alabama were recruited with the promise of receiving free medical care, meals, and burial insurance for participating in the study. Some of these men had already been infected by the bacterium while others served as a control group of individuals who had not been infected. Understanding this infection was important because it could help scientists understand the various stages and impacts of the infection, potentially leading to differential cures depending on the stage of the infection. This particular bacterium started out causing lesions—sometimes painful—and rashes. Later on, those lesions could become further infected and cause other maladies, including fever, liver inflammation, and even kidney disease, to name a few.

However, the participants enrolled were not told the whole truth about the purposes of the study. It wasn't revealed to them what infection some of them had, and they were told only that they were being treated for having "bad blood"—a condition that didn't exist. Because scientists withheld critical information regarding the study, participants had no way to provide fully informed consent to be in the research. Not only were participants not told what the actual infection was but they also were not being treated at all. Remember, the true goal was to investigate the natural progression of the infection. Participants also were not told how long the study would last. Unbeknownst to the participants, the scientists intended to continue the study until all the men had died and required that the men undergo an autopsy after death in order to receive those funeral benefits that were promised. About 15 years later, an accepted treatment for the infection was widely available (penicillin), but it was not given to the participants. Treatment was not the goal of the study.

Thirty years after the start of the study, only 74 of the "participants" were alive. In the process, 40 spouses of the men were infected with the bacterium and 19 of their children were born with a life-threatening infection.1 The Tuskegee Syphilis Study lasted 40 years total (1932 to 1972); only in 1972 when an Associated Press story caused a public outcry did the Assistant Secretary for Health and Scientific Affairs appoint an Ad Hoc Advisory Panel to review the study. Thus, for 40 years, blacks were taken advantage of, lied to on many levels, denied available treatment, and unknowingly passing on the sexually transmitted infection to their loved ones.

The social memory of this horrific and unethical study is alive and well in black communities, especially in the Deep South.2-4 The unethical nature of this study, in part, has resulted in severe distrust in medical research, especially by minorities.5 This distrust is not limited to blacks, but extends to other vulnerable underserved groups including Hispanics and Native Americans.

While many important changes have been made in overseeing the ethical administration of research studies, many minorities still do not want to participate in medical or psychological research. As a result, the majority of research has been conducted in non-Hispanic whites because of convenience sampling. Perhaps because non-Hispanic whites were not targeted in such unethical studies, they do not have the social memory and negative associations with research and so are more willing to take the chances of participating in new studies in the name of science and medicine.

Unfortunately, the hesitance among minorities has had a large negative impact on advances in medicine and health care for their communities. While we are all humans, sometimes differences matter. Women have a different psychological perspective on the world than do men, behave differently than men, and react differently to medical treatments than men. Likewise, different races and ethnicities also bring with them unique perspectives, behaviors, and reactions to the world. In terms of health disparities, chronic kidney disease disproportionately affects minority men compared with white men.6 Lung cancer disproportionately affects blacks and Native Hawaiians compared with non-Hispanic whites, even after adjusting for critical factors such as smoking behaviors.7

Because our aging population is growing quickly, another critical health issue is the increase in age-related neurodegenerative diseases such as Alzheimer's disease (AD). Yet again, minorities, including blacks, appear to be disproportionately affected by AD, with some estimating a two to four times greater likelihood of getting the disease compared with non-Hispanic whites.8-10

Supporting this risk assessment, a recent meta-analysis investigated six population studies that followed both blacks and non-Hispanic whites over time to see the rate at which each group was diagnosed with AD.11 The analysis found a 64% higher incidence rate of AD for blacks than for non-Hispanic whites but also concluded that the reasons for this greater risk are unknown.

The researchers speculated that the risk might be related to biological, psychological, and socioeconomic factors. This conclusion boils down to the notion that anything and everything might put blacks at greater risk than non-Hispanic whites.

As scientists, we have so many unanswered questions about these health disparities because when vulnerable groups do not have access to health care and research, we also cannot acquire answers to the origins of these health disparities. The legacy that the Tuskegee Syphilis Study left has created a divide between minorities and scientists (including minority scientists) that remains to this day. At the University of Alabama and other universities in the Deep South, we experience these difficulties firsthand, and, in response, regional and national programs have been developed to help bridge this historical and attitudinal gap between community members and scientists and, ultimately, help reduce these health disparities such as the increased risk for AD.12,13

A New Framework for Health Disparities
As an ongoing aim to increase awareness and understanding of health disparities, the National Institute on Aging recently developed a framework highlighting the multiple factors that may cause a variety of racial health disparities.14 They too proposed that these populationwide health disparities might be caused by biological, behavioral, sociocultural, and environmental factors. In their framework, they went into further detail and outlined 62 specific factors within 12 general categories that might influence health disparities in hopes of guiding researchers to better understand these risks.

Thirty-five of these 62 specific factors were either directly or indirectly related to psychological or physical stressors. These stressors ranged from elevated exposure to toxins, residential segregation, access to and quality of health care, prejudice and racism, more smoking and alcohol usage, greater cardiovascular disease and inflammation incidence, and different cellular responses to stress and senescence. Could it be the case that these stressors, often experienced to a greater extent by minorities than non-Hispanic whites, contribute to accelerated aging and increase the risk of being diagnosed with AD?

Stressors on the Brain
AD is a neurogenerative disease that targets critical brain structures involved in learning and memory. Do stressors impact these same brain regions?

Research has shown that chronic stress can cause direct structural damage to neurons and initiates inflammation and oxidative structural damage (both of which are evidenced in AD).15 On MRI scans, the effects of stress can be seen by shrunken brains in key areas of the brain responsible for memory such as the hippocampus.16,17

The hippocampus is one of the earliest regions to show neurodegeneration before overt AD symptoms appear, known as preclinical AD.18 Studies investigating brain activity using functional MRI have shown that chronic stress reduces brain activity in the hippocampus and in the prefrontal cortex (responsible for attention).19,20 It has even been proposed that chronic stress reduces the brain's ability to resist subtle brain damage and increases the brain's vulnerability to pathological toxins.21,22 If these toxins build over time, they can lead to cell death.

Therefore, stress might lead to forming a brain environment that is vulnerable to AD pathology and accelerates declines in attention and memory known to be impacted first in AD.

Early Signs of Racial Health Disparities in Preclinical AD
Recently, my lab proposed that any or all of the aforementioned stressors could create a selective neurobiological vulnerability among blacks.23 This vulnerability could take the form of greater accumulation of AD-related pathology—in the form of a sticky, toxic protein known as beta-amyloid—or take the form of greater neurodegeneration (eg, smaller brain volumes or a thinner cortex). A group of cognitively normal older adults participated in a study that measured brain structure, AD pathology (beta-amyloid), and cognition. A group of blacks were matched with a group non-Hispanic whites on various factors including age, sex, years of education, mental status, verbal IQ, and white matter damage.

We found that cognitively normal older blacks in the sample did not have higher levels of beta-amyloid deposition than did non-Hispanic whites. This finding suggests that blacks might not be more likely to develop AD pathology. However, the story was different when comparing blacks and non-Hispanic whites who had abnormally elevated levels of beta-amyloid, thus being classified as being in the preclinical stage of AD. Blacks with elevated beta-amyloid deposition exhibited greater neurodegeneration in the majority of brain regions known to decline in AD compared with non-Hispanic whites who also had elevated beta-amyloid deposition.

This finding suggests that blacks might have more or faster neurodegeneration than do non-Hispanic whites. Neurodegeneration in these brain regions also were associated with an older age, which is a known risk factor of AD.24 This pattern might indicate that blacks are farther along in the AD process than are non-Hispanic whites.

Since blacks and whites were matched on a variety of basic factors, why might blacks show accelerated neurodegeneration?

To answer this question, it might be helpful to look at the amount of white matter damage present in the same group of participants. This link is critical because white matter damage is often due to cardiovascular disease risks, and blacks often have higher rates of untreated hypertension and diabetes than do non-Hispanic whites.25,26 Moreover, studies have found that cardiovascular disease risks have a stronger relationship with the severity of white matter damage among blacks than among non-Hispanic whites, suggesting that race can be a critical factor that moderates how external factors such as stress affect the brain.27

In our study, greater white matter damage was associated with smaller brains (ie, more neurodegeneration). Therefore, our findings point to the likelihood that comorbid cardiovascular disease in blacks might accelerate the AD process. One limitation to the study is that it did not measure any of the various forms of physical or psychological stressors that are known to lead to both cardiovascular risk and other brain vulnerabilities.

While many more links need to be made between stressors, the cardiovascular system, the brain, and various stages of AD, our working hypothesis is that race-related adversities are major contributing factors that make key brain regions more vulnerable to brain atrophy and may contribute to advanced biological aging.

Our hope is that scientists and minority members of the community can open a dialog about the important role that minorities have in advancing research and medicine. As scientists, we must learn from experiences such as the Tuskegee Syphilis Study to approach vulnerable groups with sensitivity, compassion, and honesty to ensure that members of the community and scientists can be partners in future research to help reduce and eliminate health disparities such as the elevated risk for being diagnosed with deadly diseases like AD.

— Ian McDonough, PhD, is an assistant professor in the psychology department at the University of Alabama and an associate of the Alabama Research Institute on Aging. He received his PhD from the University of Chicago and did a postdoc at the Center for Vital Longevity at the University of Texas at Dallas. In his first year as faculty, he received the Matilda White Riley Early Stage Investigator Honors from the National Institutes of Health and was accepted into the highly competitive Butler-Williams Scholars Program at the National Institute on Aging. McDonough's current research focuses on the neural correlates of memory and how they differ with old age. More recently, he's begun investigating how the brain differs in middle-aged and older adults at risk for Alzheimer's disease, with a particular focus on racial/ethnic health disparities. This work has garnered him the 2017 Charles Barkley Health Disparities Research Investigator Award.

References
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