Racially and Ethnically Diverse Patients Less Likely to Have Amyloid Plaques Necessary for Alzheimer's Treatment

Fewer Black, Hispanic and Asian patients meet biomarker qualifications for landmark treatments that may slow the progression of Alzheimer’s disease by targeting amyloid plaques, according to new findings published in JAMA Neurology.

Anti-amyloid monoclonal antibodies break down amyloid plaques in the brain to potentially slow the progression of Alzheimer’s disease and offer patients and their providers an option for the elusive, debilitating disease, especially when the disease is diagnosed in earlier stages.

Yet a comprehensive study of 17,000 Medicare beneficiaries found Black, Hispanic and Asian patients are more likely than white counterparts to present with dementia rather than mild cognitive impairment (MCI), a disease which is often a precursor to more advanced cognitive decline. Additionally, these populations are less likely in either the MCI or dementia stages to have amyloid in their brains as confirmed by PET scans.

The disparity carries potentially significant implications for patients who begin the new therapies since the efficacy is expected to be most significant in earlier stages of cognitive decline, said first author Consuelo Wilkins, professor of Medicine and Senior Vice President for Health Equity and Inclusive Excellence at Vanderbilt University Medical Center. The study was led by VUMC, UC San Francisco and the Alzheimer’s Association. The higher rates of dementia, yet lower rates of amyloid positivity among Black and Hispanic people, may reflect differences in the causes of cognitive impairment.

“Our findings illustrate the urgency of understanding the underlying causes of memory loss in racially and ethnically diverse communities. These populations have higher rates of hypertension and diabetes, which are associated with vascular diseases of the brain. There are far-reaching implications on the patients and their families, if new treatments are less effective because they are less likely to have amyloid PET positivity,” said Wilkins. 

The cohort is thought to be the largest multisite study of differences in amyloid deposition among Asian, Black, Hispanic and white participants with dementia or MCI. The participants were enrolled in the Imaging Dementia — Evidence for Amyloid Scanning (IDEAS) study, which assessed the value of PET scans in diagnosing and treating dementia and MCI.

Minorities had lower odds of having amyloid PET positivity, with Asian people 53%, Hispanic people 32% and Black people 29% less likely than white people to have positive amyloid.

The researchers used two different analytic strategies because of the overall low number of Black, Hispanic and Asian people in the study — highlighting the need to ensure future studies are designed to boost the enrollment of people with highest burden of disease, Wilkins said.

These differences between racial and ethnic groups likely reflect social disadvantages, experiences with discrimination and racism and other social factors, not underlying differences in biology or genetics, Wilkins said.

“Lack of access to diagnosis and care at an early stage of disease could further exacerbate disparities in dementia care and outcome,” said senior author Gil Rabinovici, MD, of the  UCSF Memory and Aging Center and the Department of Neurology. “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.”

The prevalence of Alzheimer’s disease is projected to nearly triple in the coming decades. The disease impacts Black and Hispanic people at a higher rate than white counterparts. However, Asian Americans have lower age-adjusted rates of dementia of any cause.

The findings spotlight the well-documented disparity in incidence, and the complexity of discovering therapeutics to treat the disease rather than the symptoms. Other factors identified by the study as increasing the odds of amyloid PET positivity were older age, female sex and higher education. Living alone and a history of diabetes decreased the odds of amyloid PET positivity.

“Amyloid PET scans have established value in detecting amyloid plaques and contributing to an accurate and earlier Alzheimer’s diagnosis, as well as enrolling the right individuals in clinical trials,” said Maria Carrillo, Alzheimer’s Association chief science officer and co-author of this study. “However, this research is telling us that some individuals from underrepresented populations have been inaccurately diagnosed with Alzheimer’s and may have a different form of dementia, more likely vascular in origin.”

“We need more research, which is why the Alzheimer’s Association is leading a follow-up to the IDEAS study, known as New IDEAS, to study the use of amyloid PET scans in the diagnosis of Alzheimer’s for racially and ethnically diverse individuals with memory loss,” said Carrillo.

New medications for Alzheimer’s disease are rare. Clinical trials mostly focus on two hallmark protein abnormalities: amyloid plaques and tau tangles. The findings by Wilkins and colleagues underscore the necessity of identifying new pathways to treat the disease, which is the mission of the Vanderbilt Memory and Alzheimer’s Center.

“The impact of Alzheimer’s disease is on a growth trajectory in the coming years. Understanding the biological underpinnings of the disease, and the different ways it starts and develops is central to finding effective therapies that turn the tide in our ability to treat patients. The work of Dr. Angela Jefferson and our colleagues at the Vanderbilt Memory and Alzheimer’s Center is pivotal to the broader community of researchers, and of course the families we support,” said Wilkins.

The IDEAS trial was funded by the Alzheimer’s Association, the American College of Radiology, Avid Radiopharmaceuticals Inc (a wholly owned subsidiary of Eli Lilly and Company), GE Healthcare and Life Molecular Imaging (formerly Piramal Imaging).  Wilkins received funding from the National Institute on Aging (P20AG068082), the National Center for Advancing Translational Sciences (UL1TR002243 and U24TR001579) and the West End Home Foundation. Rabinovici reported receiving funding for this work from the National Institute on Aging (R35-AG072362) and the Alzheimer’s Association (ZEN-21-848216).