A new study from Washington University School of Medicine in St. Louis shows that three experimental blood tests used to identify people in the early stages of Alzheimer’s disease perform differently in black individuals compared to white individuals.
The study showed that the fourth blood test -; PrecivityAD test, commercially available in the US and Europe through C2N Diagnostics -; They were equally effective in detecting early Alzheimer’s disease regardless of the gender of the person being tested. Because the intervals between normal and abnormal test scores are typically determined based on predominantly white volunteers, tests that perform differently in black than in the white population put black patients at a disproportionate risk of misdiagnosis and receiving inappropriate medical care.
The study was published April 21 in the journal Neurology.
Most people are not diagnosed with Alzheimer’s disease until they become disoriented and confused. Such cognitive symptoms appear relatively late in the course of the disease, a decade or more after the onset of brain alteration. Scientists are working to identify people early using blood tests that detect proteins linked to Alzheimer’s disease in the blood, also known as biomarkers. But the field of Alzheimer’s biomarker research relies on data collected from groups of predominantly white participants, raising concerns about whether tests based on these biomarkers are equally valid in diverse populations.
When using a limited study population – ; As scientists, unfortunately, have traditionally done in Alzheimer’s disease research -; Then try to apply the findings to everyone, including people from diverse backgrounds, as it may exacerbate health inequalities. I hope this paper helps clarify the need to increase the diversity of participants in Alzheimer’s studies. My colleagues and I are developing a much larger, multicenter study to better assess racial differences in blood biomarkers associated with Alzheimer’s disease. This is a top priority for us.”
Susan Schindler, MD, PhD, lead author, associate professor of neurology
The study was not designed to find out why certain biomarkers of Alzheimer’s disease lead to different outcomes in black individuals than in white individuals, but the presence of other health conditions could play a role. In this study, black participants were more likely than white participants to have high blood pressure (67% vs 45%) and diabetes (28% vs 5%). Both conditions are linked to Alzheimer’s disease and may affect the performance of biomarker tests, the researchers said.
The PrecivityAD test uses high-resolution mass spectrometry to measure the proportion of the Alzheimer’s proteins amyloid beta-42 and amyloid-beta-40, as well as apolipoprotein E (APOE), a protein that influences the risk of Alzheimer’s disease. The underlying technology behind the PrecivityAD test was developed at the University of Washington in the lab of Randall J. Bateman, MD, Professor Charles F. C2N, the manufacturer of the PrecivityAD test, is a Washington University start-up headquartered in St. Louis.
The researchers analyzed the accuracy of PrecivityAD and blood tests for two other proteins -; Neurofilament light protein and two forms of tau protein -; In 76 pairs of white and non-white participants. Pairs were created by opting out of a group of volunteers who participate in research studies through the Charles F. risk of genetic variant APOE. More than 90% of individuals do not have cognitive impairment.
The researchers determined whether each individual had brain changes due to Alzheimer’s disease using brain scans, analysis of the cerebrospinal fluid that surrounds the brain and spinal cord, or both. High levels of amyloid plaques found on brain scans or certain changes in cerebrospinal fluid are standard evidence of Alzheimer’s disease.
Only the PrecivityAD test accurately categorized people by Alzheimer’s status regardless of specific race. The other three blood tests were not accurate in classifying people by Alzheimer’s status. Worse, they also performed differently in black individuals than in white individuals.
said co-author Thomas Karicari, PhD, assistant professor in the Department of Psychiatry and Neurochemistry at the University of Gothenburg in Gothenburg, Sweden. Karikari is originally from Ghana. “for example, APOE It is a very good predictor of Alzheimer’s disease in people of European ancestry, but for people of non-European ancestry, it may not be a good indicator. We have to study these risk models in a diverse group of people to understand where they work, where they don’t, and what factors influence the performance of these models.”
Schindler and Karicari said that “race criteria,” or the calibration of tests separately for each race, is not a satisfactory solution to the problem of differences in biomarkers across ethnic groups. Such a practice can create or increase racial disparities. For example, through 2021, the NFL routinely used standardized sprint cognitive tests to assess former players for cognitive impairments associated with field injuries. Such tests have consistently underestimated the degree of vulnerability of black players, making it difficult for them to obtain adequate compensation. John C. Morris, MD, the Harvey A. and Dorisma Hacker-Friedman Professor of Neurology, said University of Washington clinicians do not use the criteria for race when assessing cognitive function. Morris is Knight ADRC Director and co-author of the paper.
“Rather than trying to adjust to race in some way, it would be better to use tests that perform equally well in all individuals,” Schindler said. “Instead, we can try to understand the underlying factors that create these apparent racial differences and adapt to those underlying factors rather than race. What we don’t want to do is use these tests without evaluating their performance in diverse groups, because then we would fail in our duty to deliver The best possible care for everyone.”
University of Washington College of Medicine
Schindler, SE, et al. (2022) Effect of race on prediction of brain amyloidosis with plasma Aβ42/Aβ40, phosphorylated tau, and neurofilament light. Neurology. doi.org/10.1212/WNL.0000000000200358.