@article{01effe2d0fc54052972b6b0a315344fd,
title = "Undetectable gadolinium brain retention in individuals with an age-dependent blood-brain barrier breakdown in the hippocampus and mild cognitive impairment",
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",
author = "Axel Montagne and Huuskonen, {Mikko T.} and Gautham Rajagopal and Sweeney, {Melanie D.} and Nation, {Daniel A.} and Farshid Sepehrband and D'Orazio, {Lina M.} and Harrington, {Michael G.} and Chui, {Helena C.} and Meng Law and Toga, {Arthur W.} and Zlokovic, {Berislav V.}",
note = "Funding Information: Authors' contributions: A.M. and B.V.Z. designed the research study and analyzed and interpreted the data. A.M., G.R., and F.S. performed the experiments and analyzed the data. L.M.D., M.G.H., H.C.C., M.L., and A.W.T. recruited the participants and performed and provided the imaging scans. M.T.H., M.D.S., D.A.N., M.G.H., H.C.C., M.L., and A.W.T. provided critical reading of the manuscript. A.M. and M.T.H. contributed to manuscript writing and B.V.Z. wrote the manuscript. This study was funded by the National Institutes of Health grants 5P01AG052350 (Zlokovic/Toga), and 5P50AG005142 (Chui), in addition to the Alzheimer's Association strategic 509279 grant (Zlokovic/Toga) and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Funding Information: Authors' contributions: A.M. and B.V.Z. designed the research study and analyzed and interpreted the data. A.M. G.R. and F.S. performed the experiments and analyzed the data. L.M.D. M.G.H. H.C.C. M.L. and A.W.T. recruited the participants and performed and provided the imaging scans. M.T.H. M.D.S. D.A.N. M.G.H. H.C.C. M.L. and A.W.T. provided critical reading of the manuscript. A.M. and M.T.H. contributed to manuscript writing and B.V.Z. wrote the manuscript. This study was funded by the National Institutes of Health grants 5P01AG052350 (Zlokovic/Toga), and 5P50AG005142 (Chui), in addition to the Alzheimer's Association strategic 509279 grant (Zlokovic/Toga) and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Publisher Copyright: {\textcopyright} 2019 the Alzheimer's Association",
year = "2019",
month = dec,
doi = "10.1016/j.jalz.2019.07.012",
language = "English",
volume = "15",
pages = "1568--1575",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons",
number = "12",
}