Gray matter maturation and cognition in children with different APOE ε genotypes
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Nicole Sur and Dr. Mausaminben Hathidara
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Article
Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive declineRui Wang, Laura Fratiglioni, Erika J. Laukka et al.Neurology, February 11, 2015 -
Article
Cerebral microbleeds are related to loss of white matter structural integritySaloua Akoudad, Marius de Groot, Peter J. Koudstaal et al.Neurology, October 30, 2013 -
Article
Apolipoprotein E genotype and in vivo amyloid burden in middle-aged HispanicsPriya Palta, Brady Rippon, Christiane Reitz et al.Neurology, August 26, 2020 -
Articles
Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriersR.J. Caselli, A.C. Dueck, D.E.C. Locke et al.Neurology, April 18, 2011