TY - JOUR
T1 - Selective D2 receptor PET in manganese-exposed workers
AU - Criswell, Susan R.
AU - Warden, Mark N.
AU - Nielsen, Susan Searles
AU - Perlmutter, Joel S.
AU - Moerlein, Stephen M.
AU - Sheppard, Lianne
AU - Lenox-Krug, Jason
AU - Checkoway, Harvey
AU - Racette, Brad A.
N1 - Funding Information:
Funding for this project was provided by the following NIH grants: R01ES021488, K23ES021444, K24ES017765, R01ES013743, R01ES021488-02S1, P42ES004696, and ICTS UL1RR024992, as well as the American Parkinson Disease Association (APDA), and the Greater St. Louis Chapter of the APDA.
Funding Information:
S. Criswell reports grant funding from the NIH, including K23ES021444 and R01ES013743. M. Warden reports no disclosures relevant to the manuscript. S. Searles Nielsen reports grant funding from the NIH, including K24ES017765 and R01ES021488, and grants from the Michael J. Fox Foundation and American Parkinson Disease Association. J. Perlmutter reports grant funding from the NIH, including R01ES021488 and R01ES013743. S. Moerlein reports grant funding from the NIH, including R01ES021488. L. Sheppard reports grant funding from NIH, including R01ES026187 and R01ES021488. J. Lenox-Krug reports no disclosures relevant to the manuscript. H. Checkoway reports grant funding from the NIH, including R01ES021488, R21ES026084, R01ES025991, and R01ES025792. B. Racette reports grant funding from NIH, including K24ES017765, R01ES021488, R01ES013743, P42ES004696, and UL1RR024992, as well as grant funding from APDA and the Michael J. Fox Foundation. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018/9/11
Y1 - 2018/9/11
N2 - Objective To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [11C](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 (p < 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.
AB - Objective To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [11C](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 (p < 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.
UR - http://www.scopus.com/inward/record.url?scp=85058871383&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000006163
DO - 10.1212/WNL.0000000000006163
M3 - Article
C2 - 30097475
AN - SCOPUS:85058871383
SN - 0028-3878
VL - 91
SP - E1022-E1030
JO - Neurology
JF - Neurology
IS - 11
ER -