Julie Steenhuysen, Reuters, July 31, 2023
Groundbreaking treatments for Alzheimer’s disease that work by removing a toxic protein called beta amyloid from the brain may benefit whites more than Black Americans, whose disease may be driven by other factors, leading Alzheimer’s experts told Reuters.
The two drugs – Leqembi, from partner biotech firms Eisai and Biogen, and an experimental treatment developed by Eli Lilly, donanemab – are the first to offer real hope of slowing the fatal disease for the 6.5 million Americans living with Alzheimer’s.
Although older Black Americans have twice the rate of dementia as whites, they were screened out of clinical trials of these drugs at a higher rate, according to interviews with 10 researchers as well as 4 Eisai and Lilly executives.
Prospective Black volunteers with early disease symptoms did not have enough amyloid in their brain to qualify for the trials, the 10 researchers explained.
Hispanics, who experience dementia at one and a half times the rate of whites, were also excluded at a somewhat higher rate due to low amyloid, though the issue was not as pronounced as for Black people, five of the researchers said.
The growing evidence of a disparity around amyloid, a defining characteristic of Alzheimer’s, is raising questions among some scientists about who will benefit from the two new treatments – the first ever proven to slow the rate of cognitive decline, the researchers said.
Referring to Leqembi, Dr. Crystal Glover, a social psychologist and expert in equity in aging research who leads clinical trial recruitment of the Rush Alzheimer’s Disease Research Center in Chicago, asked: “Is this even applicable to the groups that are most at risk?”
Some researchers are asking whether Black patients are experiencing dementia due to causes other than Alzheimer’s or whether the disease manifests differently in diverse populations who have higher rates of chronic conditions.
The disparity in beta amyloid is adding to evidence that some health metrics may not work the same in diverse populations as they do in white people.
Alzheimer’s researchers have moved away from using outward signs, such as memory loss, for identifying patients with the disease towards detecting Alzheimer’s-associated proteins in the body, including amyloid, that can occur long before dementia sets in.
Yet some tests that are used to identify these proteins may perform differently among Black and white patients.
Differences in the drivers of Alzheimer’s were noted in a small 2015 study comparing brains of Black and white individuals who died of the disease.
The study, led by Dr Lisa Barnes, who is also at the Rush Center, found that white people were more likely to carry Alzheimer’s associated proteins as the primary driver of their dementia. Among Black people who died of Alzheimer’s, their dementia was more likely to result from multiple causes, such as vascular disease.
Two researchers told Reuters one possible explanation for the differences in amyloid is APOE4, a variant of a gene that regulates amyloid deposits in the brain and that is associated with a greater risk of late-onset Alzheimer’s. The risk of developing the disease among people with the variant is higher in those of Asian or European ancestry and lower in people of African and Hispanic ancestry, according to the National Institutes of Health (NIH).
In the United States, more than 75% of Black Americans are overweight or obese, increasing their risk of hypertension, high cholesterol, type 2 diabetes and sleep apnea – factors that raise the risk of vascular dementia, according to US government data. Socioeconomic factors play a role in obesity, and may also play a role in dementia.
A number of recent studies are finding that racism, and resulting inequities in income, access to high-quality medical care and healthy food, exposure to pollution and chronic stress affect the health and possibly the underlying biology of different populations.