The effect of the ApoE genotype on the association between head circumference and cognition

The aim of this study was to examine the effect of the ApoE genotype on the association between head circumference (HC) and cognition. Design: Cross-sectional factorial design in which Korean version of Mini Mental State Examination (K-MMSE) score was the dependent variable with ApoE4 status as one factor and HC as the other. Settings: A longitudinal cohort study of the Korea Health 21 R&D Project Clinical Research Center for Dementia. Participants: A total of 1,902 Koreans (599 men and 1303 women) aged over 60 years. Measurements: Cognitive function was assessed by the K-MMSE. HC and ApoE genotyping were carried out on all subjects. Results: The HC was correlated with the K-MMSE scores (r = 0.22, df = 1,525, p < 0.01), age (r = -0.11, df = 1,521, p < 0.01), educational level (r = 0.30, df = 1,525, p < 0.01), height (r = 0.50, df = 1,384, p < 0.01), and weight (r = 0.49, df = 1,445, p < 0.01). On analysis of covariance, the interaction of ApoE with HC on K-MMSE was observed after adjusting for the age, sex, educational level, height, and weight (F = 2.527, df = 4, 1, 364, p = 0.039). A test of simple main effect according to ApoE status showed that, in the ApoE epsilon 4(-) group, the mean of K-MMSE between HC quintile was not different (F = 0.517, df = 4, 1,148, p < 0.723). But in the ApoE epsilon 4(+) group, the mean of K-MMSE between HC quintile was significantly different. (F = 4.163, df = 4, 211, p < 0.003). Conclusion: All these findings suggest the possibility that the presence of ApoE epsilon 4 affects cognitive function only when the brain reserve is low. In other words, these findings support the structural brain reserve hypothesis, and the effects are more pronounced in genetically predisposed individuals.