ArticleNeurology2016
Gray matter maturation and cognition in children with different APOE ε genotypes.
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In one paragraph
Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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60citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 3% of its field
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.Biological psychiatry · 2023Pooled it
- Shared genetic architecture between Alzheimer's disease and brain morphology.Alzheimer's research & therapy · 2026Article
- Case Report of Dual Variants inClinical case reports · 2026Article
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
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- A physically and mentally active lifestyle relates to younger brain and cognitive age.GeroScience · 2026Article
- Human Apolipoprotein E ε4 Allele Modulates Energy Substrate Availability, Seizure Burden, Mortality and Hippocampal Injury, Cell Death, and Inflammation after Neonatal Hypoxic-Ischemic Brain Injury.Developmental neuroscience · 2026Article
- ModelingFrontiers in genetics · 2026Article
- Dynamic functional connectivity and transcriptomic signatures reveal stage-dependent brain network dysfunction in Alzheimer's disease spectrum.Alzheimer's research & therapy · 2025Article
- Apolipoprotein E (APOE) Genotype and Cognitive Outcomes of Snoring in a Large Cohort of Adolescents.The Laryngoscope · 2025Article
- APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.Stem cell reports · 2025Article
- Childhood Trauma andmedRxiv : the preprint server for health sciences · 2025Article
- First establishment of population-specific brain volume reference standards for Chinese children and adolescents: an AI-based segmentation study.Frontiers in pediatrics · 2025Article
- Low premorbid IQ may exacerbate the cognitive effects of apolipoprotein ε4 (APOE ε4): a multi-ethnic cross-sectional study from HABS-HD.Frontiers in neurology · 2025Article
- Apolipoprotein-E4: risk of severe malaria and mortality and cognitive impairment in pediatric cerebral malaria.Pediatric research · 2024Article
- Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure.Translational psychiatry · 2024Review
- A comprehensive analysis of APOE genotype effects on human brain structure in the UK Biobank.Translational psychiatry · 2024Article
- A lifetime perspective on risk factors for cognitive decline with a special focus on early events.Cerebral circulation - cognition and behavior · 2024Article
- Independent and combined effects of methamphetamine use disorders and APOEε4 allele on cognitive performance and brain morphometry.Addiction (Abingdon, England) · 2023Article
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 1 country.
Linda ChangFrom 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.
Vanessa DouetFrom 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.
Cinnamon BlossFrom 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.
Kristin LeeFrom 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.
Alexandra PritchettFrom 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.
Terry L JerniganFrom 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.
Natacha AkshoomoffFrom 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.
Sarah S MurrayFrom 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.
Jean FrazierFrom 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.
David N KennedyFrom 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.
David G AmaralFrom 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.
Jeffrey GruenFrom 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.
Walter E KaufmannFrom 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.
B J CaseyFrom 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.
Elizabeth SowellFrom 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.
Thomas ErnstFrom 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.
Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium
Cornell University · USUniversity of Hawaii System · USQueen's Medical Center · USUniversity of California, Davis · USUniversity of Massachusetts Chan Medical School · USUniversity of Southern California · USUniversity of Hawaiʻi at Mānoa · USBoston Children's Hospital · USHarvard University · USUniversity of California, San Diego · USYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MRESEARCH DESIGN, BIOSTATISTICS AND RESEARCH ETHICS COREG12MD007601 · NIMHD · UNIVERSITY OF HAWAII AT MANOA · PI BERRY, MARLA J · 2012 to 2016
$13.0MCreating a Pediatric Imaging-Genomics Data ResourceRC2DA029475 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, LINDA, DALE, ANDERS M · 2009 to 2011
$9.1MImaging Studies in Neurotoxicity and NeurodevelopmentU54NS056883 · NINDS · UNIVERSITY OF HAWAII AT MANOA · PI CHANG, LINDA · 2007 to 2011
$8.4MExposing the Deep Content of the Publication: Knowledge Extraction for Neuroimaging in Child PsychiatryR01MH083320 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FRAZIER, JEAN A, KENNEDY, DAVID NELSON · 2009 to 2020
$6.3MNeuroimaging and Mentoring in Drug Abuse ResearchK24DA016170 · NIDA · UNIVERSITY OF HAWAII AT MANOA · PI CHANG, LINDA · 2003 to 2013
$1.8MNCATS NIH HHS UL1 TR001863NIDA NIH HHS K24 DA016170NIDA NIH HHS RC2 DA029475NIMHD NIH HHS G12 MD007601NIMH NIH HHS R01 MH083320NINDS NIH HHS U54 NS056883
Abstract
objectiveThe 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.
methodsA 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).
resultsAmong 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.
conclusionsOur 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.
Indexed as
CognitionAdolescentAgingAnisotropyApolipoprotein E4BrainChildChild, PreschoolCross-Sectional StudiesFemaleGenotypeGray MatterHumansMagnetic Resonance ImagingMaleNeuropsychological TestsApolipoprotein E4
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