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Abstract
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.
GLOSSARY
- AD=
- Alzheimer disease;
- FA=
- fractional anisotropy;
- GAF=
- genetic ancestry factor;
- GAM=
- general additive model;
- PING=
- Pediatric Imaging, Neurocognition, and Genetics;
- ROI=
- region of interest;
- SES=
- socioeconomic status;
- WM=
- working memory
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
PING Study Consortium coinvestigators are listed on the Neurology® Web site at Neurology.org.
Supplemental data at Neurology.org
Editorial, page 558
- Received September 17, 2015.
- Accepted in final form March 28, 2016.
- © 2016 American Academy of Neurology
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