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Articles
May 12, 2014
Letter to the Editor

Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers

This article has been corrected.
VIEW CORRECTION
May 13, 2014 issue
82 (19) 1716-1723

Abstract

Objective:

To test the effects of lifetime occupational solvent exposure, as measured by dose and timing, on performance on multiple cognitive tests among retired French utility workers.

Methods:

A total of 2,143 retirees in the GAZEL cohort underwent cognitive testing in 2010. Lifetime exposure to chlorinated solvents, petroleum solvents, and benzene was assessed using a job exposure matrix. We modeled effects of lifetime solvent dose, timing of last exposure, and a combination of these metrics on risk for cognitive impairment.

Results:

Thirty-three percent of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. High exposure to solvents was significantly associated with poor cognition; for example, those highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination (risk ratio 1.18; 95% confidence interval 1.06, 1.31), the Digit Symbol Substitution Test (1.54; 1.31, 1.82), semantic fluency test (1.33; 1.14, 1.55), and the Trail Making Test B (1.49; 1.25, 1.77). Retirees at greatest risk for deficits had both high lifetime exposure to solvents and were last exposed 12 to 30 years before testing. Risk was somewhat elevated among those with high lifetime exposure who were last exposed 31 to 50 years before testing. Those with high, recent exposure exhibited impairment in almost all domains, including those not typically associated with solvent exposure.

Conclusions:

While risk of cognitive impairment among moderately exposed workers may attenuate with time, this may not be fully true for those with higher exposure. This has implications for physicians working with formerly solvent-exposed patients as well as for workplace exposure limit policies.

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Supplementary Material

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Letters to the Editor
27 May 2014
Long-term brain effects of solvent exposure
Heikki Savolainen, Professor

This elegant paper by Sabbath et al. confirms the earlier notion that all effects of chronic solvent toxicity do not disappear during cessation of the exposure. [1] The differences in the toxic properties of the solvent molecules may be decisive in the various clinical pictures. [2,3] The mechanisms may be related to the loss of cortical microcolumns, reactive gliosis, and even demyelination. It seems that even the newer water miscible solvents show toxic potential. [4]

1.Sabbath EL, Gutierrez L, Okechukwu CA, et al. Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers. Neurology 2014; 82: 1716-1723.

2. Savolainen H. Neurotoxicity of industrial chemicals and contaminants: Aspects of biochemical mechanisms and effects. Arch Toxicol 1982; Suppl 5: 71

3. Savolainen H. Toxicological mechanisms in acute and chronic nervous system degeneration. Acta neurol Scandinav 1982;66; Suppl 92: 23.

4. Laitinen J, Liesivuori J, Savolainen H. Urinary NAG and GAG as biomarkers of renal effects in exposure to 2-alkoxyalcohols and their acetates. J Occup Environ Med 1998;40: 595.

For disclosures, contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 82Number 19May 13, 2014
Pages: 1716-1723
PubMed: 24821933

Publication History

Received: October 24, 2013
Accepted: February 10, 2014
Published online: May 12, 2014
Published in print: May 13, 2014

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Disclosure

E. Sabbath, L. Gutierrez, and C. Okechukwu report no disclosures relevant to the manuscript. A. Singh-Manoux receives research support from the NIH (NIA R01AG013196 [PI], R01AG034454 [PI]). H. Amieva reports no disclosures relevant to the manuscript. M. Goldberg received a grant from the Agence Nationale de la Recherche (WORKAGE ANR-08-BLAN-0028-01). M. Zins received a grant from the Agence Nationale de la Recherche (WORKAGE ANR-08-BLAN-0028-01). C. Berr received a grant from the Agence Nationale de la Recherche (WORKAGE ANR-08-BLAN-0028-01). Go to Neurology.org for full disclosures.

Study Funding

This work is part of a project funded by the Agence Nationale de la Recherche (ANR, French National Research Agency), and Agence Française de Sécurité Sanitaire de l'Environnement et du Travail (AFSSET, French Agency for Sanitary Security of Environment and Work). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors

Affiliations & Disclosures

Erika L. Sabbath, ScD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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1.
1) Archives des Maladies Professionnelles et de l�Environnement, Scientific committee member, 2013-present
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1.
NONE
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1.
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1.
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1.
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1.
NONE
Research Support, Government Entities:
1.
1) NIA, 1 R01 AG040248-02, Research analyst, 2011-2016
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1) MacArthur Foundation Network on an Aging Society
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1.
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Laure-Anne Gutierrez, MS
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
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1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
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1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
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1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
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1.
NONE
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1.
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Cassandra A. Okechukwu, ScD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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1.
NONE
Patents:
1.
NONE
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1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH-NIA (3U01AG027669-06S1) 05/10-07/12 co-investigator NIOSH 2U19OH008861-05 09/10-08/15 co-investigator
Research Support, Academic Entities:
1.
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1.
NONE
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Archana Singh-Manoux, PhD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Epidemiology & Community Health (Associate Editor, since 2011)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) MRC UK K013351, Co-I, 2012-2016; (2) NIH/NIA R01AG013196, PI, 2009-2014; (3) NIH/NIA R01AG034454, PI, 2009-2014; (4) MRC UK K013351, Co-I, 2013-2017
Research Support, Academic Entities:
1.
NONE
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1.
NONE
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1.
NONE
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Hélène Amieva, PhD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
UCB pharma, meeting speaker, 2013 IPSEN, travel funding, 2012, 2013
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
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1.
NONE
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Marcel Goldberg, MD, PhD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Agence Nationale de la Recherche, France, Grant ANR-08- BLAN-0028-01, PI, 2009-2012
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
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Marie Zins, MD, PhD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
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NONE
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Gigascience, associate editor, since 2012
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NONE
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NONE
Other Activities:
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NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Inserm TGIR Cohortes, PI, 2010-2012 (2) Agence nationale de la recherche, French government,ANR-11-INBS-0002, PI, 2011-2019
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Claudine Berr, MD, PhD
From the Harvard Center for Population and Development Studies (E.L.S.), Cambridge, MA; INSERM U1061 (L.-A.G., C.B.), Neuropsychiatrie: recherche épidemiologique et clinique, Université Montpellier I, Hôpital La Colombière, France; Department of Society, Human Development, and Health (C.A.O.), Harvard School of Public Health, Boston, MA; INSERM U1018 (A.S.-M.), Centre for Research in Epidemiology and Population Health, AP-HP; University of Bordeaux (H.A.), ISPED, Centre INSERM U897-Epidemiologie-Biostatistique; University of Bordeaux (H.A.), Department of Psychology, Bordeaux; Population-based Cohort Platform (M.G., M.Z.), Epidemiology and Public Health Research Center, UMRS INSERM 1018, Villejuif; Université Versailles Saint-Quentin UMRS 1018 (M.G., M.Z.); CMRR Languedoc Roussillon (C.B.), CHU Montpellier, France.
Disclosure
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NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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Menber of editorial advisory board Revue Epid�miologie et Sant� publique Associate editor British Journal of Nutrition
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
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Notes

Correspondence to Dr. Sabbath: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. Sabbath coformulated hypotheses, coguided analyses, and drafted the manuscript. Ms. Gutierrez performed all statistical analyses in collaboration with Drs. Sabbath and Berr. Dr. Okechukwu edited the manuscript. Drs. Singh-Manoux and Amieva edited the manuscript and provided expertise on the neuropsychological assessment instruments. Drs. Goldberg and Zins codirect the GAZEL cohort and edited the manuscript. Dr. Berr oversaw the cognitive data collection, coformulated hypotheses, oversaw analyses, and edited the manuscript.

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