Selective D2 Receptor PET in Manganese-Exposed Workers

Details

• Personal Author:
  Checkoway, Harvey ; Criswell SR ; Lenox-Krug J ; Moerlein SM ; Perlmutter JS ; Racette BA ; Searles Nielsen S ; Sheppard L ; Warden MN
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Manganese Nervous System Occupational Exposure Occupational Health Safety
• Keywords:
  Imaging Techniques Neurotoxicity Nuclear Medicine Occupational Exposure Parkinsonism
• ISSN:
  0028-3878
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Missouri ; OSHA Region 10 ; OSHA Region 7 ; OSHA Region 9 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  91
• Issue:
  11
• NIOSHTIC Number:
  nn:20055234
• Citation:
  Neurology 2018 Sep; 91(11):e1022-e1030
• Email:
  racetteb@wustl.edu
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5)
• Federal Fiscal Year:
  2018
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Neurology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b4966409fdc1f72b46d161c9b34974b1c0449b492dba3207accfc98d94ecb7103d1987ef0609267da4f44711e5d07d42ca726d51f98057e9cfaa6fc1905556f3
• Download URL:
  https://stacks.cdc.gov/view/cdc/217582/cdc_217582_DS1.pdf
• File Type:
  [PDF - 485.24 KB ]