APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

Diddier Prada; Elena Colicino; Melinda C. Power; Marc G. Weisskopf; Jia Zhong; Lifang Hou; Avron Spiro; Pantel Vokonas; Kasey Brenan; Luis A. Herrera; Joel Schwartz; Andrea A. Baccarelli

doi:10.1016/j.envres.2016.07.034

APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

Diddier Prada, Elena Colicino, Melinda C. Power, Marc G. Weisskopf, Jia Zhong, Lifang Hou, Avron Spiro, Pantel Vokonas, Kasey Brenan, Luis A. Herrera, Joel Schwartz, Andrea A. Baccarelli^*

^*Corresponding author for this work

Preventive Medicine

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

14 Scopus citations

Abstract

Background Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. Methods We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. Results An interquartile range (IQR:14.23 μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: −0.11 to −0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: −0.97 to −0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: −0.11, 95%CI: −0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. Conclusions Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

Original language	English (US)
Pages (from-to)	101-105
Number of pages	5
Journal	Environmental Research
Volume	151
DOIs	https://doi.org/10.1016/j.envres.2016.07.034
State	Published - Nov 1 2016

Funding

This study was funded by the National Institute of Environmental Health Sciences (NIEHS) ( R01ES021733 and R01ES015172 ). The US Department of Veterans Affairs (VA) Normative Aging Study (NAS) is supported by the VA Cooperative Studies Program/ERIC, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Additional support to the VA-NAS was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510 ). DP is financially supported by CONACYT-México , and the Fundación México en Harvard . AS3 is supported by a VA Clinical Sciences Research and Development Senior Research Career Scientist award. Funding sources had no involvement in study design, collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication.

Keywords

APOE-epsilon ε4 allele
Age-related
Aging
Cognitive decline
Lead
ε4ε4 haplotype

ASJC Scopus subject areas

General Environmental Science
Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.envres.2016.07.034

Cite this

@article{b69d35ce44f144e585d8b0441a44b821,

title = "APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals",

abstract = "Background Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. Methods We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. Results An interquartile range (IQR:14.23 μg/g) increase in tibia lead concentration was associated with a 0.06 (95\% confidence interval [95\%CI]: −0.11 to −0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95\%CI: −0.97 to −0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: −0.11, 95\%CI: −0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. Conclusions Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.",

keywords = "APOE-epsilon ε4 allele, Age-related, Aging, Cognitive decline, Lead, ε4ε4 haplotype",

author = "Diddier Prada and Elena Colicino and Power, \{Melinda C.\} and Weisskopf, \{Marc G.\} and Jia Zhong and Lifang Hou and Avron Spiro and Pantel Vokonas and Kasey Brenan and Herrera, \{Luis A.\} and Joel Schwartz and Baccarelli, \{Andrea A.\}",

note = "Funding Information: This study was funded by the National Institute of Environmental Health Sciences (NIEHS) ( R01ES021733 and R01ES015172 ). The US Department of Veterans Affairs (VA) Normative Aging Study (NAS) is supported by the VA Cooperative Studies Program/ERIC, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Additional support to the VA-NAS was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510 ). DP is financially supported by CONACYT-M{\'e}xico , and the Fundaci{\'o}n M{\'e}xico en Harvard . AS3 is supported by a VA Clinical Sciences Research and Development Senior Research Career Scientist award. Funding sources had no involvement in study design, collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = nov,

day = "1",

doi = "10.1016/j.envres.2016.07.034",

language = "English (US)",

volume = "151",

pages = "101--105",

journal = "Environmental Research",

issn = "0013-9351",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

AU - Prada, Diddier

AU - Colicino, Elena

AU - Power, Melinda C.

AU - Weisskopf, Marc G.

AU - Zhong, Jia

AU - Hou, Lifang

AU - Spiro, Avron

AU - Vokonas, Pantel

AU - Brenan, Kasey

AU - Herrera, Luis A.

AU - Schwartz, Joel

AU - Baccarelli, Andrea A.

N1 - Funding Information: This study was funded by the National Institute of Environmental Health Sciences (NIEHS) ( R01ES021733 and R01ES015172 ). The US Department of Veterans Affairs (VA) Normative Aging Study (NAS) is supported by the VA Cooperative Studies Program/ERIC, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Additional support to the VA-NAS was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510 ). DP is financially supported by CONACYT-México , and the Fundación México en Harvard . AS3 is supported by a VA Clinical Sciences Research and Development Senior Research Career Scientist award. Funding sources had no involvement in study design, collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. Publisher Copyright: © 2016 The Authors

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. Methods We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. Results An interquartile range (IQR:14.23 μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: −0.11 to −0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: −0.97 to −0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: −0.11, 95%CI: −0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. Conclusions Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

AB - Background Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. Methods We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. Results An interquartile range (IQR:14.23 μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: −0.11 to −0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: −0.97 to −0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: −0.11, 95%CI: −0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. Conclusions Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

KW - APOE-epsilon ε4 allele

KW - Age-related

KW - Aging

KW - Cognitive decline

KW - Lead

KW - ε4ε4 haplotype

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JO - Environmental Research

JF - Environmental Research

ER -

APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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