Abstract
Apolipoprotein E (APOE) is an important risk factor for cognitive decline and Alzheimer’s disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer’s and dementia, while the e2 allele has a positive effect on longevity, and possibly on preservation of cognitive function. Education also has an important effect on cognition and longevity but the interplay between APOE and education is not well-characterized. Previous studies of the effect of APOE on cognitive decline often used linear regression with the normality assumption, which may not be appropriate for analyzing bounded and skewed neuropsychological test scores. In this paper, we applied Bayesian beta regression to assess the effect of APOE alleles on cognitive decline in a cohort of centenarians with longitudinal assessment of their cognitive function. The analysis confirmed the negative association between older age and cognition and the beneficial effect of education that persists even at the extreme of human lifespan in carriers of the e3 allele. In addition, the analysis showed an association between APOE and cognition that is modified by education. Surprisingly, an antagonistic interaction existed between higher education and APOE alleles, suggesting that education may reduce the positive effect of APOE e2 and increase the negative effect of APOE e4 at extreme old age.
Highlights
Declines of certain cognitive abilities are common complications of aging and identifying risk factors for cognitive decline is essential to search for therapeutic interventions
The three alleles differ in two amino acids and result in proteins produced by the e2 and e3 alleles that bind to high-density lipoprotein cholesterol (HDL) while e4 binds to very-low-density lipoprotein (VLDL)
In this work, we examined the association of e2 and e4 alleles of apolipoprotein E (APOE) with cognitive function in centenarians enrolled in the New England Centenarian Study (NECS) (Sebastiani and Perls, 2012), who are enriched for carriers of the e2 allele, have varying levels of education, and for whom we have longitudinally collected assessments of cognitive function
Summary
Declines of certain cognitive abilities are common complications of aging and identifying risk factors for cognitive decline is essential to search for therapeutic interventions. Known risk factors for cognitive decline include older age, lower education, and genes such as apolipoprotein E (APOE) that plays an important role in the risk for Alzheimer’s disease (Fan et al, 2019). Examining the interaction between education and APOE alleles could help to better characterize the long term effect of education on cognition and the interplay between genetic and environmental risk factors. In this work, we examined the association of e2 and e4 alleles of APOE with cognitive function in centenarians enrolled in the New England Centenarian Study (NECS) (Sebastiani and Perls, 2012), who are enriched for carriers of the e2 allele, have varying levels of education, and for whom we have longitudinally collected assessments of cognitive function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
