Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ε4 allele
Justin Remer,
Douglas C. Dean, III,
Kewei Chen,
Rebecca A. Reiman,
Matthew J. Huentelman,
Eric M. Reiman,
Sean C.L. Deoni
Affiliations
Justin Remer
Advanced Baby Imaging Lab, Rhode Island Hospital, Providence, RI, USA; Department of Pediatrics, Warren Alpert Medical School at Brown University, Providence RI, USA; Corresponding author at: Advanced Baby Imaging Lab, Rhode Island Hospital, Providence, RI, USA.
Douglas C. Dean, III
Department of Pediatrics, University of Wisconsin–Madison, Madison WI 53705 USA; Department of Medical Physics, University of Wisconsin–Madison, Madison WI 5305 USA; Waisman Center, University of Wisconsin–Madison, Madison WI 53705 USA
Kewei Chen
Arizona Alzheimer's Consortium, University of Arizona School of Medicine, Tucson and Phoenix AZ, USA; Banner Alzheimer's Institute, Phoenix, AZ, USA; University of Arizona College of Medicine, Phoenix, AZ, USA; Arizona State University, Phoenix, AZ, USA
Rebecca A. Reiman
Banner Alzheimer's Institute, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
Matthew J. Huentelman
Banner Alzheimer's Institute, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
Eric M. Reiman
Arizona Alzheimer's Consortium, University of Arizona School of Medicine, Tucson and Phoenix AZ, USA; Banner Alzheimer's Institute, Phoenix, AZ, USA; University of Arizona College of Medicine, Phoenix, AZ, USA; Arizona State University, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
Sean C.L. Deoni
Advanced Baby Imaging Lab, Rhode Island Hospital, Providence, RI, USA; Department of Pediatrics, Warren Alpert Medical School at Brown University, Providence RI, USA; Maternal, Newborn, and Child Health Discovery and Tools, Bill and Melinda Gates Foundation; Seattle WA, USA
We have previously demonstrated cross-sectional differences in magnetic resonance imaging (MRI) measurements of white matter myelin and gray matter in infants with or without the apolipoprotein ε4 allele, a major genetic risk factor for late-onset Alzheimer's disease (AD). In this study, we sought to compare longitudinal MRI white matter myelin and cognitive-behavioral changes in infants and young children with and without this allele. Serial MRI and cognitive tests were obtained on 223 infants and young children, including 74 ε4 carriers and 149 non-carriers, 2–68 months of age, matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated brain mapping algorithms and non-linear mixed models were used to characterize and compare trajectories of white matter myelin and cognitive-behavioral test scores. The APOE ε4 carriers had statistically significant differences in white matter myelin development, in the uncinate fasciculus, temporal lobe, internal capsule and occipital lobe. Additionally, ε4 carriers had a slightly greater rate of development in early learning composite a surrogate measure of IQ representative of expressive language, receptive language, fine motor, and visual skills, but displayed slightly lower non verbal development quotient scores a composite measure of fine motor and visual skills across the entire age range. This study supports the possibility that ε4 carriers have slightly altered rates of white matter and cognitive development in childhood. It continues to raise questions about the role of APOE in human brain development and the relevance of these developmental differences to the predisposition to AD.
