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

Axel Montagne; Mikko T Huuskonen; Gautham Rajagopal; Melanie D Sweeney; Daniel A Nation; Farshid Sepehrband; Lina M D'Orazio; Michael G Harrington; Helena C Chui; Meng Law; Arthur W Toga; Berislav V Zlokovic

doi:10.1016/j.jalz.2019.07.012

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

Alzheimers Dement. 2019 Dec;15(12):1568-1575. doi: 10.1016/j.jalz.2019.07.012.

Affiliations

¹ Zilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² 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.
³ Laboratory of Neuro Imaging (LONI), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ 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.
⁵ Huntington Medical Research Institute, Pasadena, CA, USA.
⁶ 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.
⁷ 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. Electronic address: zlokovic@usc.edu.

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: Blood-brain barrier; Gadolinium; Magnetic resonance imaging; Mild cognitive dysfunction; Normal aging.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Blood-Brain Barrier / drug effects*
Brain / pathology
Cognitive Dysfunction / pathology*
Contrast Media / administration & dosage
Female
Gadolinium* / analysis
Gadolinium* / therapeutic use
Hippocampus / pathology*
Humans
Magnetic Resonance Imaging*
Male
Neuropsychological Tests / statistics & numerical data

Substances

Contrast Media
Gadolinium

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding