Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

Christopher J. Brubaker; Vincent J. Schmithorst; Erin N. Haynes; Kim N. Dietrich; John C. Egelhoff; Diana M. Lindquist; Bruce P. Lanphear; Kim M. Cecil

doi:10.1016/j.neuro.2009.07.007

Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

Christopher J. Brubaker, Vincent J. Schmithorst, Erin N. Haynes, Kim N. Dietrich, John C. Egelhoff, Diana M. Lindquist, Bruce P. Lanphear, Kim M. Cecil

Epidemiology & Environmental Health

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

109 Scopus citations

Abstract

Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9 ± 1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

Original language	English
Pages (from-to)	867-875
Number of pages	9
Journal	NeuroToxicology
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.neuro.2009.07.007
State	Published - Nov 2009

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health, NIEHS P01 ES011261, NIEHS R01 ES015559, NIEHS R21 ES013524, NCI R01 CA112182, M01 RR08084 from the General Clinical Research Centers Program, and the Environmental Protection Agency R82938901.

Keywords

Corona radiata
Corpus callosum
Internal capsule
Myelination

ASJC Scopus subject areas

General Neuroscience
Toxicology

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10.1016/j.neuro.2009.07.007

Cite this

@article{3455c5ce9e28497cad956a4ef5ce629c,

title = "Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study",

abstract = "Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9 ± 1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.",

keywords = "Corona radiata, Corpus callosum, Internal capsule, Myelination",

author = "Brubaker, {Christopher J.} and Schmithorst, {Vincent J.} and Haynes, {Erin N.} and Dietrich, {Kim N.} and Egelhoff, {John C.} and Lindquist, {Diana M.} and Lanphear, {Bruce P.} and Cecil, {Kim M.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health, NIEHS P01 ES011261, NIEHS R01 ES015559, NIEHS R21 ES013524, NCI R01 CA112182, M01 RR08084 from the General Clinical Research Centers Program, and the Environmental Protection Agency R82938901.",

year = "2009",

month = nov,

doi = "10.1016/j.neuro.2009.07.007",

language = "English",

volume = "30",

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T2 - A diffusion tensor imaging study

AU - Brubaker, Christopher J.

AU - Schmithorst, Vincent J.

AU - Haynes, Erin N.

AU - Dietrich, Kim N.

AU - Egelhoff, John C.

AU - Lindquist, Diana M.

AU - Lanphear, Bruce P.

AU - Cecil, Kim M.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health, NIEHS P01 ES011261, NIEHS R01 ES015559, NIEHS R21 ES013524, NCI R01 CA112182, M01 RR08084 from the General Clinical Research Centers Program, and the Environmental Protection Agency R82938901.

PY - 2009/11

Y1 - 2009/11

N2 - Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9 ± 1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

AB - Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9 ± 1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

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KW - Corpus callosum

KW - Internal capsule

KW - Myelination

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JO - NeuroToxicology

JF - NeuroToxicology

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ER -

Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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