Reduced brain activity during a working memory task in middle-aged apolipoprotein E ε4 carriers with overweight/obesity.

Objective: The apolipoprotein E ε4 (APOE ε4) allele and midlife obesity are independent risk factors for Alzheimer's disease (AD). Both of these risk factors are also associated with differences in brain activation, as measured by blood oxygenation level-dependent (BOLD) responses, in the absence of detectable cognitive deficits. Although the presence of these risk factors may influence brain activity during working memory tasks, no study to date has examined whether the presence of the ε4 allele explains variation in working memory brain activity while matching for levels of overweight/obesity. The primary aim of this study was to determine whether the presence of the ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation in adults with overweight/obesity. We predicted that ε4 carriers would have greater brain activation in regions that support working memory. Methods: This ancillary study included 48 ( Results: Compared to non-ε4 carriers with overweight/obesity, ε4 carriers with overweight/obesity had lower fMRI brain activity in the middle frontal gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, lateral occipital cortex, and angular gyrus ( Conclusion: These results indicate that presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is related to altered brain activity during a working memory paradigm, which may confer risk for accelerated neurocognitive decline in late adulthood. Future research is needed to clarify the clinical implications of these findings in the context of risk for AD.