Delayed Amyloid Onset May Help Explain Racial Differences in Alzheimer’s Biomarker Positivity

A multicenter longitudinal cohort study of 2,653 US adults found that Black participants had a later estimated age of mean amyloid onset than White participants. The findings suggest that time relative to estimated amyloid onset, rather than chronological age alone, may help researchers analyze racial differences and improve representation in Alzheimer disease trials.

Estimated amyloid onset was about 12.5 years later in Black participants.
Overall amyloid positivity was lower among Black participants.
Amyloid accumulation rates did not significantly differ between groups.
Time relative to estimated onset may inform trial analyses.

Researchers conducted a retrospective, multicenter longitudinal cohort study using harmonized amyloid PET and cognitive data from 2,653 middle-aged and older adults at five US academic institutes. Participants included 406 self-identified Black and 2,247 White individuals. The study assessed amyloid burden, cognition and the estimated age of mean amyloid onset (AMAO), including analyses matched for major covariates.

Estimated AMAO was about 12.5 years later for Black than White participants in both unmatched and matched analyses. Overall amyloid positivity was lower among Black participants (24.1% vs 31.7%), but within almost every interval relative to group-specific expected years to onset, positivity was higher among Black participants. Adjusted longitudinal rates of amyloid accumulation did not significantly differ between groups before or after AMAO. Black participants had more vascular comorbidities (56.9% vs 39.3%) and showed cognitive decline before AMAO, unlike White participants.

The authors suggest expected years to amyloid onset may be useful when analyzing racial differences and setting Alzheimer trial eligibility criteria. These observational findings do not establish a clinical threshold or show that changing trial criteria improves representation; estimates may also be affected by cohort selection and the study’s model-based onset measure.

In practice

For researchers designing or interpreting Alzheimer disease prevention and treatment trials, these findings suggest that chronological age alone may not adequately account for group differences in amyloid positivity. In this cohort, Black participants had an estimated mean amyloid onset about 12.5 years later, and their overall amyloid positivity was lower, despite higher positivity than White participants in most intervals measured relative to expected onset. Expected years to onset may merit evaluation as an analytic or eligibility measure, but this retrospective cohort does not validate a threshold or demonstrate that using it improves trial representation.

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Source

JAMA Network Open: Simpson’s Paradox, Amyloid Paradox, and Racial Differences ↗

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