Article
Interaction between APOE ε4 genotype and educational attainment and its impact on mild cognitive impairment in the Heinz Nixdorf Recall Study
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Published: | February 26, 2021 |
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Background: Studies have identified the apolipoprotein E (APOE) ε4 genotype to be a genetic risk factor for mild cognitive impairment (MCI), an early stage of Alzheimer's disease. Research further indicated that environmental factors might modify the genetic effect on MCI, with high education being the most studied protective factor for MCI. The aim of this study was to investigate possible interaction of APOE ε4 status and educational attainment on MCI.
Methods: Information on education, MCI and APOE status was available for 3829 participants (50% female; aged 50-80 years) from the first follow-up examination of the prospective population-based Heinz Nixdorf Recall study. MCI was defined according to the current International Working Group on MCI criteria [1]. Logistic regression models were fitted to estimate sex- and age-adjusted odds ratios (OR) and 95% confidence intervals (95%-CI). Next to separately assessing the association of education (<14 years vs. ≥14 years of formal education; according to the International Classification of Education [ISCED-97]) and APOE status (carrier vs. noncarrier) with MCI, the effect of APOE on MCI was additionally stratified by educational groups. Interaction terms were included to assess APOExeducation interaction on the multiplicative scale. To consider interaction on the additive scale, the relative excess risk due to interaction (RERI) was calculated.
Results: In the study population, 559 participants were defined as having MCI (prevalence: 14.6%). A higher chance of MCI was observed for reporting <14 years of formal education (OR: 1.37 [95%-CI: 1.11, 1.69]) and having a positive APOE ε4 status (OR: 1.27 [95%-CI: 1.04, 1.55]). Stratified analysis showed a stronger genetic effect of APOE ε4 status on MCI in participants with <14 years of formal education (OR: 1.42 [95%-CI: 1.12, 1.79)], compared to participants with ≥14 years of formal education (OR: 1.00 [95%-CI: 0.67, 1.45)]. An indication for positive interaction between education and APOE ε4 status on MCI was found on the additive scale (RERI: 0.52 [95%-CI: 0.01, 1.03]), while no interaction on the multiplicative scale was observed.
Conclusion: Study results gave indication for positive interaction on the additive scale of APOE ε4 status and educational attainment, showing stronger genetic effects on MCI in groups of low education. Socioeconomically disadvantaged environments and health behaviors related to low educational attainment may be responsible for an altered APOE ε4 expression.
The authors declare that they have no competing interests.
The authors declare that an ethics committee vote is not required.
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