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Undetectable gadolinium brain retention in individuals with an age-dependent blood-brain barrier breakdown in the hippocampus and mild cognitive impairment

  • Axel Montagne
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Mikko T. Huuskonen
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Gautham Rajagopal
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Melanie D. Sweeney
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Daniel A. Nation
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Department of Psychology, University of Southern California, Los Angeles, CA, USA
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  • Farshid Sepehrband
    Affiliations
    Laboratory of Neuro Imaging (LONI), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Lina M. D'Orazio
    Affiliations
    Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Michael G. Harrington
    Affiliations
    Huntington Medical Research Institute, Pasadena, CA, USA
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  • Helena C. Chui
    Affiliations
    Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Meng Law
    Affiliations
    Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Arthur W. Toga
    Affiliations
    Laboratory of Neuro Imaging (LONI), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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  • Berislav V. Zlokovic
    Correspondence
    Corresponding author. Tel.: 323.442.2722; Fax: 323.666.2184.
    Affiliations
    Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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      Abstract

      Introduction

      Blood-brain barrier (BBB) breakdown is an early independent biomarker of human cognitive dysfunction, as found using gadolinium (Gd) as a contrast agent. Whether Gd accumulates in brains of individuals with an age-dependent BBB breakdown and/or mild cognitive impairment remains unclear.

      Methods

      We analyzed T1-weighted magnetic resonance imaging (MRI) scans from 52 older participants with BBB breakdown in the hippocampus 19-28 months after either cyclic or linear Gd agent.

      Results

      There was no change in T1-weighted signal intensity between the baseline contrast MRI and unenhanced MRI on re-examination in any of the studied 10 brain regions with either Gd agent suggesting undetectable Gd brain retention.

      Discussion

      Gd does not accumulate in brains of older individuals with a BBB breakdown in the hippocampus. Thus, Gd agents can be used without risk of brain retention within a ∼2-year follow-up to study BBB in the aging human brain in relation to cognition and/or other pathologies.

      Keywords

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