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

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	1568-1575
Number of pages	8
Journal	Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume	15
Issue number	12
DOIs	https://doi.org/10.1016/j.jalz.2019.07.012
Publication status	Published - Dec 2019

Keywords / Materials (for Non-textual outputs)

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

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10.1016/j.jalz.2019.07.012

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Montagne, A., Huuskonen, M. T., Rajagopal, G., Sweeney, M. D., Nation, D. A., Sepehrband, F., D'Orazio, L. M., Harrington, M. G., Chui, H. C., Law, M., Toga, A. W., & Zlokovic, B. V. (2019). Undetectable gadolinium brain retention in individuals with an age-dependent blood-brain barrier breakdown in the hippocampus and mild cognitive impairment. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 15(12), 1568-1575. https://doi.org/10.1016/j.jalz.2019.07.012

@article{8b73eb29094a47b5999b4d29438e327e,

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

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}",

year = "2019",

month = dec,

doi = "10.1016/j.jalz.2019.07.012",

language = "English",

volume = "15",

pages = "1568--1575",

journal = "Alzheimer's & Dementia: The Journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Wiley",

number = "12",

}

Montagne, A, Huuskonen, MT, Rajagopal, G, Sweeney, MD, Nation, DA, Sepehrband, F, D'Orazio, LM, Harrington, MG, Chui, HC, Law, M, Toga, AW & Zlokovic, BV 2019, 'Undetectable gadolinium brain retention in individuals with an age-dependent blood-brain barrier breakdown in the hippocampus and mild cognitive impairment', Alzheimer's & Dementia: The Journal of the Alzheimer's Association, vol. 15, no. 12, pp. 1568-1575. https://doi.org/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. / Montagne, Axel; Huuskonen, Mikko T; Rajagopal, Gautham et al.
In: Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Vol. 15, No. 12, 12.2019, p. 1568-1575.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Undetectable gadolinium brain retention in individuals with an age-dependent blood-brain barrier breakdown in the hippocampus and mild cognitive impairment

AU - Montagne, Axel

AU - Huuskonen, Mikko T

AU - Rajagopal, Gautham

AU - Sweeney, Melanie D

AU - Nation, Daniel A

AU - Sepehrband, Farshid

AU - D'Orazio, Lina M

AU - Harrington, Michael G

AU - Chui, Helena C

AU - Law, Meng

AU - Toga, Arthur W

AU - Zlokovic, Berislav V

PY - 2019/12

Y1 - 2019/12

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Blood-Brain Barrier/drug effects

KW - Brain/pathology

KW - Cognitive Dysfunction/pathology

KW - Contrast Media/administration & dosage

KW - Female

KW - Gadolinium/analysis

KW - Hippocampus/pathology

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Neuropsychological Tests/statistics & numerical data

U2 - 10.1016/j.jalz.2019.07.012

DO - 10.1016/j.jalz.2019.07.012

M3 - Article

C2 - 31862169

SN - 1552-5260

VL - 15

SP - 1568

EP - 1575

JO - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

JF - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

IS - 12

ER -

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

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Keywords / Materials (for Non-textual outputs)

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