The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades

Neuroimaging shows brain-functional differences due to apolipoprotein E (APOE) polymorphisms may exist decades before the increased risk period for Alzheimer's disease, but little is known about their effect on cognition and brain function in children and young adults. This study assessed 415 healthy ɛ2 and ɛ4 carriers and matched ɛ3/ɛ3 controls, spanning ages 6–65, on a range of cognitive tests. Subjects were also compared on a new dynamical measure of EEG activity during a visual working memory task using alphabetical stimuli. ɛ4 subjects had better verbal fluency compared to ɛ3, an effect that was strongest in 51–65 year-olds. No ɛ4 deficits in cognition were found. In 6–15 year-olds, there were differences in total spatio-temporal wave activity between ɛ3 and ɛ4 subjects in the theta band, approximately 200 ms post-stimulus. Differences in brain function in younger ɛ4 subjects and superior verbal fluency across the entire age range suggest that the APOE ɛ4 allele is an example of antagonistic pleiotropy.