Axel Montagne1, Mikko T Huuskonen1, Gautham Rajagopal1, Melanie D Sweeney1, Daniel A Nation2, Farshid Sepehrband3, Lina M D'Orazio4, Michael G Harrington5, Helena C Chui4, Meng Law6, Arthur W Toga3, Berislav V Zlokovic7. 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.
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.
Authors: Alexander Radbruch; Lukas D Weberling; Pascal J Kieslich; Johanna Hepp; Philipp Kickingereder; Wolfgang Wick; Heinz-Peter Schlemmer; Martin Bendszus Journal: Invest Radiol Date: 2016-11 Impact factor: 6.016
Authors: Maria Camilla Rossi Espagnet; Bruno Bernardi; Luca Pasquini; Lorenzo Figà-Talamanca; Paolo Tomà; Antonio Napolitano Journal: Pediatr Radiol Date: 2017-05-19
Authors: Janelle Drouin-Ouellet; Stephen J Sawiak; Giulia Cisbani; Marie Lagacé; Wei-Li Kuan; Martine Saint-Pierre; Richard J Dury; Wael Alata; Isabelle St-Amour; Sarah L Mason; Frédéric Calon; Steve Lacroix; Penny A Gowland; Susan T Francis; Roger A Barker; Francesca Cicchetti Journal: Ann Neurol Date: 2015-04-09 Impact factor: 10.422
Authors: Matthew R Halliday; Sanket V Rege; Qingyi Ma; Zhen Zhao; Carol A Miller; Ethan A Winkler; Berislav V Zlokovic Journal: J Cereb Blood Flow Metab Date: 2016-01 Impact factor: 6.200
Authors: Hazel I Zonneveld; Jeroen D C Goos; Mike P Wattjes; Niels D Prins; Philip Scheltens; Wiesje M van der Flier; Joost P A Kuijer; Majon Muller; Frederik Barkhof Journal: Neurology Date: 2014-01-29 Impact factor: 9.910
Authors: Axel Montagne; Samuel R Barnes; Melanie D Sweeney; Matthew R Halliday; Abhay P Sagare; Zhen Zhao; Arthur W Toga; Russell E Jacobs; Collin Y Liu; Lilyana Amezcua; Michael G Harrington; Helena C Chui; Meng Law; Berislav V Zlokovic Journal: Neuron Date: 2015-01-21 Impact factor: 17.173
Authors: Clifford R Jack; David A Bennett; Kaj Blennow; Maria C Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P Rankin; Christopher C Rowe; Philip Scheltens; Eric Siemers; Heather M Snyder; Reisa Sperling Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Philipp Eisele; Angelika Alonso; Kristina Szabo; Anne Ebert; Melissa Ong; Stefan O Schoenberg; Achim Gass Journal: Medicine (Baltimore) Date: 2016-09 Impact factor: 1.889
Authors: Giuseppe Barisano; Axel Montagne; Kassandra Kisler; Julie A Schneider; Joanna M Wardlaw; Berislav V Zlokovic Journal: Nat Cardiovasc Res Date: 2022-02-07
Authors: Axel Montagne; Samuel R Barnes; Daniel A Nation; Kassandra Kisler; Arthur W Toga; Berislav V Zlokovic Journal: Geroscience Date: 2022-04-25 Impact factor: 7.581
Authors: Xingfeng Shao; Kay Jann; Samantha J Ma; Lirong Yan; Axel Montagne; John M Ringman; Berislav V Zlokovic; Danny J J Wang Journal: Front Neurosci Date: 2020-11-30 Impact factor: 4.677
Authors: Axel Montagne; Daniel A Nation; Abhay P Sagare; Giuseppe Barisano; Melanie D Sweeney; Ararat Chakhoyan; Maricarmen Pachicano; Elizabeth Joe; Amy R Nelson; Lina M D'Orazio; David P Buennagel; Michael G Harrington; Tammie L S Benzinger; Anne M Fagan; John M Ringman; Lon S Schneider; John C Morris; Eric M Reiman; Richard J Caselli; Helena C Chui; Julia Tcw; Yining Chen; Judy Pa; Peter S Conti; Meng Law; Arthur W Toga; Berislav V Zlokovic Journal: Nature Date: 2020-04-29 Impact factor: 49.962