Abstract P330: The Association Between APOE Genotype and Dementia in the Dementia Risk Pooling Project

Introduction: Apolipoprotein E ( APOE ) is a glycoprotein that mediates and regulates lipid transport and uptake. The APOE e4 allele is associated with increased risk of mortality and Alzheimer’s Disease and related dementias. It has been suggested that the APOE e2 allele is associated with increased survival and serves as a protective factor for cognitive decline and dementia. However, due to the rarity of the e2 allele, this association is not fully understood. Furthermore, the association between APOE genotypes and dementia may differ by race/ethnicity. Methods: Data from six large, community-based, prospective cohort studies from the Dementia Risk Pooling Project (DRPP) were used. Cumulative incidence estimates for dementia and mortality by race and APOE genotype (combining one or two e2 or e4 alleles: 24, 22/23, 33, 34/44 ) were estimated. Cox regression models were used to estimate the APOE genotype ( 22, 23, 33, 34, 44 ) cause-specific hazard ratios (HRs) for dementia and mortality adjusting for age, sex, and cohort. Results: The sample consisted of 43,404 participants (average age 54, 52% female, 16% Black participants). Overall, the 5-year cumulative incidence of dementia was higher in White participants across different genotypes, while mortality rate was higher in Black participants (Figure 1). The 5-year cumulative incidence of dementia was higher among both Black and White participants with one or two e4 alleles. Using the APOE e2/e4 genotype as a reference, the dementia HRs for the e2/e2 and e2/e3 genotypes were 0.73 (95% CI 0.51-1.06) and 0.64 (95% CI 0.53-0.76), respectively. e3/e4 and e4/e4 genotypes were associated with higher HRs of 1.32 (95% CI 1.12-1.56) and 2.68 (95% CI 2.20-3.27), respectively. There was no association between APOE genotypes and mortality. Conclusion: In this large, pooled cohort, the presence of an e2 allele was associated with lower risk of dementia, while the presence of an e4 allele was associated with higher risk in both Black and White adults. APOE genotype was not associated with mortality.