TY - JOUR
T1 - [ 18 F]FDOPA positron emission tomography in manganese-exposed workers
AU - Criswell, Susan R.
AU - Nielsen, Susan Searles
AU - Warden, Mark
AU - Perlmutter, Joel S.
AU - Moerlein, Stephen M.
AU - Flores, Hubert P.
AU - Huang, John
AU - Sheppard, Lianne
AU - Seixas, Noah
AU - Checkoway, Harvey
AU - Racette, Brad A.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/1
Y1 - 2018/1
N2 - Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[ 18 F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014 min −1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012 min −1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p ≤ 0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.
AB - Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[ 18 F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014 min −1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012 min −1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p ≤ 0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.
KW - Manganese
KW - [ F]FDOPA PET
UR - http://www.scopus.com/inward/record.url?scp=85025144844&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2017.07.004
DO - 10.1016/j.neuro.2017.07.004
M3 - Article
C2 - 28694016
AN - SCOPUS:85025144844
SN - 0161-813X
VL - 64
SP - 43
EP - 49
JO - NeuroToxicology
JF - NeuroToxicology
ER -