Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
The role of polygenic risk in Alzheimer's disease prediction for African Americans.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Hutten Christina G, Beck Todd, Evans Denis, Rajan Kumar B
Аннотация
INTRODUCTION: African Americans (AAs) face a higher risk of Alzheimer's disease and related dementias (ADRD) than European Americans (EUs), yet the utility of polygenic risk scores (PRS) in AAs remains underexplored.
METHODS: A standardized dementia PRS was evaluated in the Chicago Health and Aging Project (n = 4336; 61% AA) for associations with ADRD and cognitive trajectories over 8.4 years.
RESULTS: PRS predicted ADRD more strongly in EUs (c-index 0.86) than AAs (0.77); however, it conferred higher risk in AAs (hazard ratio [HR] = 1.36, 95% confidence interval [CI]: 1.04-1.78) compared to EU (HR = 1.13, 95% CI: 0.88-1.44). The PRS remained predictive among AAs after apolipoprotein E (APOE) ε4 adjustment (HR = 1.53, 95% CI: 1.03-2.27). Higher PRS associated with lower baseline cognition and faster decline (p < 0.05).
DISCUSSION: PRS conferred greater ADRD risk in AAs and comparable rates of cognitive decline, despite stronger discrimination in EUs, adding to the limited knowledge of genetic contributions to ADRD risk among AAs beyond APOE ε4 alleles.
METHODS: A standardized dementia PRS was evaluated in the Chicago Health and Aging Project (n = 4336; 61% AA) for associations with ADRD and cognitive trajectories over 8.4 years.
RESULTS: PRS predicted ADRD more strongly in EUs (c-index 0.86) than AAs (0.77); however, it conferred higher risk in AAs (hazard ratio [HR] = 1.36, 95% confidence interval [CI]: 1.04-1.78) compared to EU (HR = 1.13, 95% CI: 0.88-1.44). The PRS remained predictive among AAs after apolipoprotein E (APOE) ε4 adjustment (HR = 1.53, 95% CI: 1.03-2.27). Higher PRS associated with lower baseline cognition and faster decline (p < 0.05).
DISCUSSION: PRS conferred greater ADRD risk in AAs and comparable rates of cognitive decline, despite stronger discrimination in EUs, adding to the limited knowledge of genetic contributions to ADRD risk among AAs beyond APOE ε4 alleles.