Apolipoprotein E (APOE) ε4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the ε4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 ± 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examination (MMSE), we examined the effects and interactions of the ε4 allele and education on the MMSE score. First, we coded education as three levels: low, middle, and high based on the formal educational levels (analysis 1). Second, to clarify the modifying effect of education, we adopted a new coding for education into two levels, considering a periodical background (around 1900) of gender differences in educational attainments (analysis 2). In analysis 1, the main effects of the ε4 allele and education on the MMSE score were significant after adjusting for age. Further, there was a significant three-way interaction effect between the ε4 allele, education, and gender on the MMSE. Analysis 2 showed that the modifying effect of the ε4 allele by education was observed only in women with the ε4 allele. These findings suggest that both the APOE ε4 allele and education appear to be associated with cognitive function even in centenarians, but the interaction between the ε4 allele and education might depend on gender in this cohort.
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