Variation in Neurodegeneration‐Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Possible pleiotropic effects of apolipoprotein E4 (APOE E4) in individuals with congenital brain malformations are relatively unknown. Our goal was to determine if neurodegeneration‐linked brain region volumes differ significantly between E4 carriers and noncarriers in young adults with spina bifida (SB).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Eleven individuals ( > 18 years), genotyped for APOE, underwent neuroimaging and neurocognitive evaluation. Primary analysis: Magnetic resonance imaging (MRI) data from 10 a priori neurodegeneration‐risk regions of interest were compared between E4 carriers and noncarriers, adjusting for age, sex, and total intracranial volume (FDR‐adjusted <jats:italic>p</jats:italic> < 0.05). Secondary analyses: Age‐adjusted neurocognitive standard scores were compared between groups (<jats:italic>p</jats:italic> < 0.05). Post hoc analyses of NeuroQuant‐derived regional brain volumes were examined for combined group differences in young adults with SB.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Comparison of a priori risk region volumes revealed significantly lower left amygdala volumes (FDR‐adjusted <jats:italic>p</jats:italic> = 0.04) in young adult E4 carriers (<jats:italic>n</jats:italic> = 4) relative to noncarriers (<jats:italic>n</jats:italic> = 7). Neurocognitive data were not significantly different between the groups. A possible trend was detected for enlarged parietal volumes in E4 carriers (<jats:italic>p</jats:italic> = 0.07), while volumetric extremes ( > 95% or < 5%) were detected for the anterior cingulate (100% of cases; <jats:italic>p</jats:italic> = 0.001), frontal cortices (90% of cases), hippocampus (80% of cases), and entorhinal cortices (70% of cases).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Early left amygdala volumetric reduction was found in E4 carriers; combined group volume comparisons revealed frontal and temporal lobe differences in young adults with SB relative to age‐ and sex‐matched volumetric estimates. This pilot investigation does not appear to support E4 conferring a pleiotropic benefit in young adults with SB but rather supports further investigation of MRI volumetrics as a possible biomarker for this population.</jats:p></jats:sec>
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Jasien, Joan M, Jacques A Stout, Mohamad A Mikati, Robert J Anderson, Brittany G Nave, Herbert E Fuchs, Brian Smith, Alexandra Badea, et al. (n.d.). Variation in Neurodegeneration‐Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida. Annals of the Child Neurology Society. 10.1002/cns3.70016 Retrieved from https://hdl.handle.net/10161/33105.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Joan Mary Jasien
Dr. Joan Mary Jasien is a Med‑Peds–trained child neurologist and neurodevelopmental disabilities specialist with board certification in Internal Medicine, Pediatrics, and Neurology. She completed her Med‑Peds residency followed by fellowship training in Child Neurology and Neurodevelopmental Disabilities before joining Duke University Medical Center.
She co‑founded and co‑directs the Children’s Cerebral Palsy–Related Conditions Clinic, the Adults with Cerebral Palsy–Related Conditions Clinic, and the Adults with Spina Bifida Clinic, and also serves as Co‑Director of the Children’s Spina Bifida Clinic. Together, these four programs form Duke’s multidisciplinary clinics for children and adults with spina bifida and cerebral palsy–related conditions. Her clinical expertise focuses on hyperkinetic movements and hypertonia in individuals with cerebral palsy and related conditions, as well as the overall cognition and functioning of individuals with spina bifida and cerebral palsy and related conditions.
Dr. Jasien’s research centers on neurological aging in individuals with spina bifida and on community engagement in research, with the goal of improving long‑term health outcomes across the lifespan.
Mohamad Abdul Mikati
Mohamad A. Mikati M.D., is the Wilburt C. Davison Professor of Pediatrics, Professor of Neurobiology, and the 2008-2025 Chief of the Division of Pediatric Neurology. Dr. Mikati’s clinical research has centered on characterization and therapy of pediatric epilepsy and neurology syndromes, describing several new pediatric neurological entities with two carrying his name (POSSUM syndromes # 3708 and 4468), developing novel therapeutic strategies for epilepsy and related disorders particularly Alternating Hemiplegia of Childhood, and applying cutting edge genetic and Magnetic Resonance Imaging techniques to drug resistant pediatric epilepsy. In the laboratory he has elucidated mechanisms of seizure related neuronal injury, particularly those related to the ceramide pathway, and demonstrated neuroprotective effects of several agents including erythropoietin. Most recently he has concentrated his laboratory research on the pathophysiology of ATP1A3 dysfunction in the brain as model for epilepsy and of Alternating Hemiplegia of Childhood. He has more than 290 peer reviewed publications, 400 abstracts 41 chapters one book and two booklets. He also has more than 10,497 citations in the literature with an h-index of 58 and an i-10index of 190. Dr. Mikati has written chapters on epilepsy and related disorders in the major textbooks of Pediatrics and Pediatric Neurology including Swaiman’s Pediatric Neurology and Nelson’s Pediatrics. Before joining Duke in 2008 he had completed his M.D. and Pediatric training at the American University of Beirut, his Neurology at the Massachusetts General Hospital, his Neurophysiology at Boston Children’s Hospital and had been on the Faculty at Harvard as Director of Research in the Epilepsy Program at Boston Children’s Hospital and then as Professor and Chairman, Department of Pediatrics, Founder and Director of the Adult and Pediatric Epilepsy Program at the American University of Beirut. Dr. Mikati has had several international leadership roles including being President of the Union of the Middle Eastern and Mediterranean Pediatric Societies, on the Standing Committee of the International Pediatric Association (IPA), Chair of the Strategic Advisory Group on Early Childhood Development of the IPA, Officer of the International Child Neurology Association, Consultant to UNICEF, WHO, and the American Board of Pediatrics. He was selected to organize and chair the American Epilepsy Society's Merritt-Putnam Symposium and was one of only two Pediatric Neurologists, initially chosen worldwide, on the WHO advisory committee for the International Classification of Disease. He has received several national and international honors including, among others, Merritt Putnam American Epilepsy Society Fellowship Award, Harvard Community Health Plan Peer recognition Award, Debs Research Award, Hamdan Award for contributions to Medicine, Hans Zellweger Award for contributions to Pediatric Neurology, Patient Choice Award and the Michael Frank Award for research and lifetime contributions to the field of Pediatric Neurology.
Alexandra Badea
I have a joint appointment in Radiology and Neurology and my research focuses on neurological conditions like Alzheimer’s disease. I work on imaging and analysis to provide a comprehensive characterization of the brain. MRI is particularly suitable for brain imaging, and diffusion tensor imaging is an important tool for studying brain microstructure, and the connectivity amongst gray matter regions.
I am interested in image segmentation, morphometry and shape analysis, as well as in integrating information from MRI with genetics, and behavior. Our approaches target: 1) phenotyping the neuroanatomy using imaging; 2) uncovering the link between structural and functional changes, the genetic bases, and environmental factors. I am interested in generating methods and tools for comprehensive phenotyping.
We use high-performance cluster computing to accelerate our image analysis. We use compressed sensing image reconstruction, and process large image arrays using deformable registration, perform segmentation based on multiple image contrasts including diffusion tensor imaging, as well as voxel, and graph analysis for connectomics.
At BIAC my efforts focus on developing multivariate biomarkers and identifying vulnerable networks based on genetic risk for Alzheimer's disease.
My enthusiasm comes from the possibility to extend from single to integrative multivariate and network based analyses to obtain a comprehensive picture of normal development and aging, stages of disease, and the effects of treatments. I am working on multivariate image analysis and predictive modeling approaches to help better understand early biomarkers for human disease indirectly through mouse models, as well as directly in human studies.
I am dedicated to supporting an increase in female presence in STEM fields, and love working with students. The Bass Connections teams involve undergraduate students in research, providing them the opportunity to do independent research studies and get involved with the community. These students have for example takes classes such as:
BME 394: Projects in Biomedical Engineering (GE)
BME 493: Projects in Biomedical Engineering (GE)
ECE 899: Special Readings in Electrical Engineering
NEUROSCI 493: Research Independent Study 1
Jeffrey Nicholas Browndyke
Dr. Browndyke is an Associate Professor of Behavioral Health & Neurosciences in the Department of Psychiatry & Behavioral Sciences. He has a secondary appointment as Assistant Professor of Cardiovascular & Thoracic Surgery.
Dr. Browndyke's research interests involve the use of advanced neurocognitive and neuroimaging techniques for perioperative contributions to delirium and later dementia risk, monitoring of late-life neuropathological disease progression, and intervention/treatment outcomes. His research also involves novel telehealth methods for remote neurocognitive evaluation and implementation of non-invasive neuromodulatory techniques to assist in postoperative recovery and dementia risk reduction.
Dr. Browndyke's clinical expertise is focused upon geriatric neuropsychology with an emphasis in the assessment, diagnosis, and treatment of dementia and related disorders in adults and US veteran patient populations.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.