Objective: The aims of the current study were to determine whether children with the 6 different APOE ϵ genotypes show differences in gray matter maturation, particularly for those with ϵ4 and ϵ2 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 ϵ 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 ϵ4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in ϵ2ϵ4 children, the lowest hippocampal fractional anisotropy in younger ϵ4ϵ4 children, the largest medial orbitofrontal cortical areas in ϵ3ϵ4 children, and age-dependent thinning of the entorhinal cortex in ϵ4ϵ4 children. Younger ϵ4ϵ4 children had the lowest scores on executive function and working memory, while younger ϵ2ϵ4 children performed worse on attention tasks. Larger parietal gyri in the younger ϵ2ϵ4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger ϵ4ϵ4 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 ϵ4-carrier children. The ϵ4ϵ4 and ϵ2ϵ4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE ϵ polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia.
ASJC Scopus subject areas
- Clinical Neurology