Title

Selective D2 receptor PET in manganese-exposed workers

Authors

Susan R. Criswell, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Mark N. Warden, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Susan Searles Nielsen, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Joel S. Perlmutter, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Stephen M. Moerlein, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Lianne Sheppard, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Jason Lenox-Krug, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Harvey Checkoway, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
Brad A. Racette, From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa. racetteb@wustl.edu.

Document Type

Article

Abstract

OBJECTIVE: To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [C](N-methyl)benperidol (NMB) PET. METHODS: We used NMB PET to evaluate 50 workers with a range of Mn exposure: 22 Mn-exposed welders, 15 Mn-exposed workers, and 13 nonexposed workers. Cumulative Mn exposure was estimated from work histories, and movement disorder specialists examined all workers. We calculated NMB D2R nondisplaceable binding potential (BPND) for the striatum, globus pallidus, thalamus, and substantia nigra (SN). Multivariate analysis of covariance with post hoc descriptive discriminate analysis identified regional differences by exposure group. We used linear regression to examine the association among Mn exposure, Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) score, and regional D2R BPND. RESULTS: D2R BPND in the SN had the greatest discriminant power among exposure groups ( < 0.01). Age-adjusted SN D2R BPND was 0.073 (95% confidence interval [CI] 0.022-0.124) greater in Mn-exposed welders and 0.068 (95% CI 0.013-0.124) greater in Mn-exposed workers compared to nonexposed workers. After adjustment for age, SN D2R BPND was 0.0021 (95% CI 0.0005-0.0042) higher for each year of Mn exposure. Each 0.10 increase in SN D2R BPND was associated with a 2.65 (95% CI 0.56-4.75) increase in UPDRS3 score. CONCLUSIONS AND RELEVANCE: Nigral D2R BPND increased with Mn exposure and clinical parkinsonism, indicating dose-dependent dopaminergic dysfunction of the SN in Mn neurotoxicity.

Medical Subject Headings

Adult; Aged; Benperidol (metabolism, pharmacology); Brain; Case-Control Studies; Female; Humans; Male; Manganese (toxicity); Manganese Poisoning (diagnostic imaging); Middle Aged; Multimodal Imaging; Neuroimaging; Parkinsonian Disorders (complications, diagnosis, metabolism); Positron-Emission Tomography; Receptors, Dopamine D2 (metabolism); Young Adult

Publication Date

9-11-2018

Publication Title

Neurology

E-ISSN

1526-632X

Volume

91

Issue

11

First Page

e1022

Last Page

e1030

PubMed ID

30097475

Digital Object Identifier (DOI)

10.1212/WNL.0000000000006163

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