A number of studies have explored the relationships of apolipoprotein E (APOE) genotype and education with dementia over the last decade. However, observations concerning the possible modifying effect of education on the APOE-dementia association are limited. The objective of this study was to test the hypothesis that education may decrease the risk of APOE ε4 on dementia. Pooled data from 3 major population-based studies in Northern Europe were used in this study, with a total of 3436 participants aged 65 and older derived from the Kungsholmen project and the Gothenburg Birth Cohort studies in Sweden, and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project in Finland. The main outcome measure was dementia, which was diagnosed in 219 persons according to standard criteria. APOE ε4 was associated with increased risk of dementia independent of the effect of education (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.4 for 1 ε4 carrier and OR, 3.7; 95% CI, 1.8-7.2 for 2 ε4 carriers). High education (8 years and more) was related to a lower dementia risk (OR, 0.5; 95% CI, 0.3-0.6). An interaction between education and APOE ε4 was observed. Compared with those with less education and no ε4, the odds of dementia among persons with low education who carried any ε4 allele was 2.7 (95% CI, 1.9-3.9), and 1.2 (0.7-1.8) if they had higher education. This study suggests that genetic (APOE ε4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE ε4 on dementia occurrence.
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