title: Gray matter maturation and cognition in children with different APOE ε genotypes.
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.
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA. lchang@hawaii.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Douet
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Cinnamon
authors.initials: C
authors.lastname: Bloss
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Lee
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pritchett
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Akshoomoff
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Jean
authors.initials: J
authors.lastname: Frazier
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: David N
authors.initials: DN
authors.lastname: Kennedy
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: David G
authors.initials: DG
authors.lastname: Amaral
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gruen
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sowell
authors.affiliation: From the Department of Medicine (L.C., V.D., K.L., A.P., T.E.), John A. Burns School of Medicine, University of Hawaii and The Queen's Medical Center, Honolulu; Department of Psychiatry, School of Medicine (C.B.), Departments of Psychiatry and Cognitive Science (T.L.J., N.A.), and Department of Pathology (S.S.M.), University of California San Diego, La Jolla; Department of Psychiatry (J.F., D.N.K.), University of Massachusetts Medical School, Boston; Department of Psychiatry and Behavioral Sciences (D.G.A.), University of California, Davis; Departments of Pediatrics and Investigative Medicine (J.G.), Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT; Boston Children's Hospital (W.E.K.), Harvard Medical School, Boston, MA; Sackler Institute for Developmental Psychobiology (B.J.C.), Weil Cornell Medical College, New York, NY; Department of Pediatrics (E.S.), University of Southern California, Los Angeles; and Children's Hospital (E.S.), Los Angeles, CA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
mesh_terms: D000293:Adolescent; D000375:Aging / Q000235:genetics / Q000473:pathology; D016880:Anisotropy; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4