A study suggestions that Asian, Black, and Hispanic patients are less likely to develop beta-amyloid plaques — a key Alzheimer's biomarker — alongside cognitive impairment. That's a big problem, considering these plaques are typically a screening requirement for participation in clinical trials for the drugs that slow Alzheimer's progression.
The majority of Alzheimer’s research to date has been conducted in white participants. For example, the first FDA-approved anti-amyloid drug to treat Alzheimer’s, Aduhelm, may or may not actually work, and some of this uncertainty ties back to its overwhelmingly white clinical trials: Only 3.6 percent of participants were Black or Hispanic, despite higher risk in these populations. And because Alzheimer’s unfolds differently in people of different races, that means the safety and efficacy of the drug was barely tested in some of the groups that need it most.
The realization of this lack of diversity in the Aduhelm trials prompted calls more non-white participants in future drug trials. Last week, Aduhelm’s manufacturers Eisai and Biogen announced the successful trial of the next drug in their pipeline, lecanemab. They also celebrated that this drug trial series succeeded where Aduhelm’s failed: one in four lecanemab trial participants were Black or Hispanic — as opposed to a little more than three in 100.
However, according to a new study published in JAMA Neurology, the issue of clinical trial participation is a little more complex than simply improving recruitment practices getting more Black, Hispanic, Asian and indigenous participants involved.
Matching up white participants with mild cognitive impairment to Asian, Black, or Hispanic patients with similar risk factors, the researchers who conducted this recent study concluded that that non-white patients were less likely to test positive for amyloid plaques on a PET scan — and often, that disqualifies them from Alzheimer’s clinical trials where carrying this biomarker of the disease is a prequesite.
“Lack of access to diagnosis and care at an early stage of disease could further exacerbate disparities in dementia care and outcome,” said Dr. Gil Rabinovici from the UCSF Memory and Aging Center, who led the research.
To help solve for this pitfall, researchers must find ways to ensure that they are appropriately and equitably measuring Alzheimer’s disease across multiple demographics, taking into account non-white groups that may have differences in presentation, risk or disease trajectory, Jackson wrote to Being Patient in an email.
Alzheimer’s biomarkers vary by race
Not all risk factors for Alzheimer’s accurately map across all racial populations.
For example, while APOE4 is the greatest genetic risk factor for Alzheimer’s disease for white people, it doesn’t seem to be the case for American Indians. Many blood-based biomarkers are less accurate in detecting Alzheimer’s disease in Black and Hispanic individuals. Meanwhile, cognitive tests are still grappling with their racist roots, in which some practitioners apply “race-norming” adjustments based on prejudice.
Beta-amyloid is another one of these potentially race-specific biomarkers. Scientists have yet to reach agreement on the role this problematic protein plays in Alzheimer’s disease. The same goes for the question of whether the plaques themselves are indicative of cognitive decline. Many cognitively healthy older individuals develop beta-amyloid plaques in the brain, and yet, they never experience cognitive impairment.
Why is this the case? More research is needed to fully understand all the factors: Another study author, Dr. Consuelo H. Wilkins from the division of geriatric medicine at Vanderbilt University Medical Center, believed the lack of amyloid positivity in Black and Hispanic people suggested vascular dementia may be to blame. “These populations have higher rates of hypertension and diabetes, which are associated with vascular diseases of the brain,” Wilkins said. But questions remain unanswered: Wilkins’s theory about higher risk for vascular diseases in Black and Hispanic populations doesn’t explain the low rates of amyloid positivity in the Asian population.
If we can’t diagnose Alzheimer’s according to the presence of beta-amyloid plaques, what about cognitive testing?
While many now associate the amyloid plaques with an Alzheimer’s disease diagnosis, this is a relatively recent development. In 2018, the National Institute on Aging and the Alzheimer’s Association worked toward updating the definition of the disease, focusing on the neuropathology — like the appearance of these plaques in the brain — rather than the symptoms, like memory loss and dementia.
Beyond the fact that pathology differs by race, the cognitive tests developed to help diagnose Alzheimer’s and other dementias also don’t necessarily map accurately across all races. Some of them were even developed with racist beliefs at their very foundation. Ultimately, experts say, these diagnostic practices that only apply to white populations will make it harder for Black and Hispanic patients to access resources or a timely diagnosis. And that’s especially problematic, Rabinovici pointed out, when considering that these cutting-edge therapies are developed to work best in the disease’s earliest stages.
“A higher proportion of Black and Hispanic patients presented to specialists at the dementia stage, rather than at the mild cognitive impairment stage,” Rabinovici said. “But the benefit of these new therapies is expected to be greater in earlier stages of the disease.”
Meanwhile, addressing these diagnostic discrepancies will go a long way to ensuring equitable access to clinical trials and treatments for non-white patients. Presently, multiple blood tests, retinal scans, and other diagnostic tools for detecting early-stage Alzheimer’s pathology are in trials.
“Public health efforts to better diagnose and treat non-amyloid variants of dementia will be critical if we are to reduce disparities in dementia care,” Rabinovici said.
UPDATED 11:59 a.m., 7 October 2022: This article was updated to include helpful additional insights from Washington State University Alzheimer’s researcher Astrid M. Suchy-Dicey, who provided comments to Being Patient after publication.