New analysis of biomarker data from the AHEAD study shows that amyloid levels differ across ethnic groups, which may affect participant diversity in clinical trials

17/04/2024

A new study, published in the Alzheimer’s & Dementia journal, shows that people from certain ethnic groups may be ineligible for Alzheimer's disease clinical trials because they have lower levels of amyloid protein at early stages of the disease – underscoring the importance of adapting eligibility criteria to maximise inclusion and diversity. 
It has long been recognised that some of the groups most likely to get dementia, such as people from minority ethnic groups, are greatly underrepresented in clinical trials.  Underrepresentation of these groups in trials can limit the translation of study findings in the real world, as interventions may not benefit all populations at risk. Amyloid biomarker measurements are increasingly being used to determine eligibility for clinical trials, however differences in levels of amyloid biomarkers between ethnic groups could contribute to the inadvertent exclusion of these groups from studies. To understand this issue in the context of a real-world clinical trial, researchers turned to the AHEAD 3-45 study, which is designed to assess the safety and efficacy of lecanemab in preclinical (presymptomatic) Alzheimer’s disease. Biomarkers play a particularly prominent role in recruitment for these studies, at a stage of Alzheimer’s disease when symptoms are not yet present. 
Researchers from the Keck School of Medicine (Los Angeles, USA) collected blood tests and brain scans from 4,905 participants, ages 55 to 80, from a wide range of ethnic groups. Based on blood tests designed to detect levels of amyloid, non-hispanic Caucasian groups were most likely to meet eligibility cutoffs for clinical trials. People who identified as Hispanic Black, Hispanic white, non-Hispanic Asian and non-Hispanic Black were significantly less likely to be eligible for studies based on amyloid levels in the blood when compared to non-Hispanic white counterparts. Participants who were eligible based on blood tests also underwent brain PET scans that are used to directly measure amyloid buildup in the brain. Among those who met the blood test cutoff, individuals from all ethnic groups were equally likely to be eligible to participate based on PET scan data. According to the authors, This suggests that the cutoffs for eligibility are adequate, but also point to a paradox where some groups may have a higher risk of dementia but lower levels of amyloid. As a result, treating those groups may require a different approach.