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February 08, 2022; 98 (6) Research Article

Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment

Noemie Letellier, Laure-Anne Gutierrez, Corinne Pilorget, Fanny Artaud, View ORCID ProfileAlexis Descatha, View ORCID ProfileAnna Ozguler, View ORCID ProfileMarcel Goldberg, View ORCID ProfileMarie Zins, View ORCID ProfileAlexis Elbaz, View ORCID ProfileClaudine Berr
First published December 22, 2021, DOI: https://doi.org/10.1212/WNL.0000000000013146
Noemie Letellier
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Laure-Anne Gutierrez
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Corinne Pilorget
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Fanny Artaud
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Alexis Descatha
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Anna Ozguler
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Marcel Goldberg
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Marie Zins
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Alexis Elbaz
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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Claudine Berr
From INM (Institute for Neurosciences of Montpellier) (N.L., L.-A.G., C.B.), INSERM, Univ Montpellier; Santé Publique France (C.P.), Lyon; Exposome and Heredity Team (F.A., A.E.), CESP, INSERM, Paris-Saclay University, UVSQ, Gustave Roussy; Population-Based Epidemiological Cohorts Research Unit (A.D., A.O., M.G., M.Z.), INSERM, UMS 011; VIMA Aging and Chronic Diseases (A.D., M.Z.), INSERM, UVSQ, Villejuif; Institut de Recherche en Santé, Environnement et Travail, Poisoning Control Center–Clinical Data Center Angers (A.D.), INSERM, EHESP, UMR S1085, CHU Angers, Univ Angers, Univ Rennes; Université de Paris (M.G., M.Z.); and Memory Research and Resources Center, Department of Neurology (C.B.), Montpellier University Hospital Gui de Chauliac, France.
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  • ORCID record for Claudine Berr
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Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment
Noemie Letellier, Laure-Anne Gutierrez, Corinne Pilorget, Fanny Artaud, Alexis Descatha, Anna Ozguler, Marcel Goldberg, Marie Zins, Alexis Elbaz, Claudine Berr
Neurology Feb 2022, 98 (6) e633-e640; DOI: 10.1212/WNL.0000000000013146

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Abstract

Background and Objectives To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young-old adults (≥45 years).

Methods In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of 7 cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities, and executive functions (e.g., Digit Symbol Substitution Test [DSST]). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex, and education. Lifetime exposure to formaldehyde was assessed using a French Job Exposure Matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitive impairment (<25th percentile) and formaldehyde exposure (exposed/never exposed), exposure duration, cumulative exposure index (CEI), and combination of CEI and time of last exposure.

Results Among 75,322 participants (median age 57.5 years, 53% women), 8% were exposed to formaldehyde during their professional life. These participants were at higher risk of global cognitive impairment (for global cognitive score: adjusted relative risk [aRR] 1.17; 95% confidence interval [CI] 1.11–1.23), after adjusting for confounders (age, sex, education, income, solvent exposure, Effort–Reward Imbalance, night shift, repetitive work, and noisy work). They were at higher risk of cognitive impairment for all cognitive domains explored. Longer exposure duration and high CEI were associated with cognitive impairment, with a dose–effect relationship for exposure duration. Recent exposure was associated with impairment in all cognitive domains. Time did not fully attenuate formaldehyde-associated cognitive deficits especially in highly exposed individuals (for DSST: high past exposure aRR 1.23; 95% CI 1.11–1.36; high recent exposure: aRR 1.24; 95% CI 1.13–1.35).

Discussion Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.

Glossary

aRR=
adjusted relative risk;
CI=
confidence interval;
CEI=
cumulative exposure index;
DSST=
Digit Symbol Substitution Test;
ERI=
Effort–Reward Imbalance;
FCSRT=
Free and Cued Selective Reminding Test;
IQR=
interquartile range;
JEM=
Job Exposure Matrix;
MMSE=
Mini-Mental State Examination;
NAF=
Nomenclature d’Activité Française;
PCA=
principal component analysis;
PCS=
Professions et Catégories Socioprofessionnelles;
RR=
relative risk;
TMT=
Trail-Making Test;
VFT=
Verbal Fluency Task

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received June 29, 2021.
  • Accepted in final form November 16, 2021.
  • © 2021 American Academy of Neurology
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