# Manganese-Related Motor and Cognitive System Toxicity Among Professional Welders.

> **NIH ALLCDC R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $504,849

## Abstract

ABSTRACT
Millions of workers in the US and worldwide, including professional welders, experience prolonged, high-
dose occupational exposures to manganese (Mn). Over-exposure to environmental manganese (Mn) has
long been established as a cause of adverse motor system effects that have clinical features similar to
parkinsonism (PS), which is the most common clinical manifestation of Parkinson disease (PD). There is
also evidence that Mn exposure can induce dysfunction of cognitive control, mood, and behavior. The
primary goal of the proposed investigation is to perform a comprehensive clinical assessment of Mn-related
motor and cognitive system neurotoxicity among a well-characterized cohort of professional welders we
have studied for the past 13 years. Accordingly, we will extend our clinical assessments of motor system
toxicity and conduct a comprehensive battery of cognitive and behavioral tests, and estimate dose-response
relations with Mn exposure. The cognitive/behavioral battery will be a new feature of the study. We will also
test the hypothesis that plasma proteins known to be associated with PD: alpha synuclein (SNCA), protein
dyglycase (DJ1 [PARK7]), and ubiquitin carboxy-terminal esterase (UCHL1), are associated with risk,
severity, and progression of PS in the cohort. The study will be conducted among 500 (of 938) welders who
will be re-enrolled. The proposed study will be the most comprehensive clinical assessment of motor and
cognitive neurologic outcomes in an Mn-exposed cohort conducted to date. An especially novel feature of
the proposed study is characterization of protein biomarker measurements that may serve as preclinical
indicators of subsequent clinically determined parkinsonian outcomes. The findings from this research
should have important implications for setting occupational Mn exposure standards, and may ultimately
inform disease prevention strategies for Mn-related adverse neurological outcomes.

## Key facts

- **NIH application ID:** 10438147
- **Project number:** 5R01OH011661-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Harvey Checkoway
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2022
- **Award amount:** $504,849
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438147

## Citation

> US National Institutes of Health, RePORTER application 10438147, Manganese-Related Motor and Cognitive System Toxicity Among Professional Welders. (5R01OH011661-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438147. Licensed CC0.

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