Gray matter maturation and cognition in children with different APOE ε genotypes

Objective: The aims of the current study were to determine whether children with the 6 different APOE epsilon genotypes show differences in gray matter maturation, particularly for those with epsilon 4 and epsilon 2 alleles, which are associated with poorer outcomes in many neurologic disorders. Methods: A total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE epsilon genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3-tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox). Results: Among APOE epsilon 4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in epsilon 2 epsilon 4 children, the lowest hippocampal fractional anisotropy in younger epsilon 4 epsilon 4 children, the largest medial orbitofrontal cortical areas in e3e4 children, and age-dependent thinning of the entorhinal cortex in epsilon 4 epsilon 4 children. Younger epsilon 4 epsilon 4 children had the lowest scores on executive function and working memory, while younger epsilon 2 epsilon 4 children performed worse on attention tasks. Larger parietal gyri in the younger epsilon 2 epsilon 4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger epsilon 4 epsilon 4 children, predicted poorer performance on attention or working memory. Conclusions: Our findings validated and extended prior smaller studies that showed altered brain development in APOE epsilon 4-carrier children. The epsilon 4 epsilon 4 and epsilon 2 epsilon 4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE epsilon polymorphisms in young childrenmay provide the earliest indicators for individuals whomight benefit fromearly interventions or preventive measures for future brain injuries and dementia.