Race, APOE ε4, and Long-Term Cognitive Trajectories in a Biracial Population Sample

Background: The association of the APOE epsilon 4 allele with incident Alzheimer's dementia is higher among European Americans (EAs) than African Americans (AAs), but similar for the rate of cognitive decline. Objective: To examine the racial differences in the association of the APOE epsilon 4 allele with incident Alzheimer's dementia and cognitive decline. Methods: Using a population-based sample of 5,117 older adults (66% AAs and 63% females), we identified cognitive trajectory groups from a latent class mixed model and examined the association of the APOE epsilon 4 allele with these groups. Results: The frequency of the APOE epsilon 4 allele was higher among AAs than EAs (37% versus 26%). Four cognitive trajectories were identified: slow, mild, moderate, and rapid. Overall, AAs had a lower baseline global cognition than EAs, and a higher proportion had rapid (7% versus 5%) and moderate (20% versus 15%) decline, but similar mild (44% versus 46%), and lesser slow (29% versus 34%) decline compared to EAs. Additionally, 25% of AAs (13% of EAs) with mild and 5% (<1% of EAs) with slow decline were diagnosed with incident Alzheimer's dementia. The APOE epsilon 4 allele was associated with higher odds of rapid and moderate decline compared to slow decline among AAs and EAs, but not with mild decline. Conclusions: AAs had lower cognitive levels and were more likely to meet the cognitive threshold for Alzheimer's dementia among mild and slow decliners, explaining the attenuated association of the epsilon 4 allele with incident Alzheimer's dementia among AAs.