Study of Manganese Exposure in Welders Could Help in Treating Parkinson’s

A $3.7 million federal grant is funding a project aiming to clarify how exposure to manganese, a trace metal, affects the brain and causes cognitive problems.

Findings from this research may help in better understanding Parkinson’s disease.

Manganese is an essential nutrient, a mineral that is necessary in very small quantities (usually obtained from food) for the body to function. However, exposure to high amounts of manganese can cause problems in the nervous system, including movement and cognitive difficulties.

These symptoms of high manganese exposure (sometimes called manganism) are similar to Parkinson’s symptoms, possibly because both manganism and Parkinson’s are caused by similar types of damage to the brain.

Previous research has shown that high amounts of manganese can kill dopamine-producing neurons in the brain. These are the same neurons that die off in Parkinson’s disease, which is the primary cause of its motor symptoms. Therapies that replace lost dopamine (e.g., levodopa) are mainstays of treatment for both manganism and Parkinson’s.

However, while this mechanism explains motor problems in both conditions, it’s less clear how cognitive problems — such as memory issues, irritability, aggression, and confusion — arise in manganism, or in Parkinson’s.

“People think of Parkinson’s disease as a movement disorder, and it is, but cognitive problems are also very common,” Susan Criswell, MD, a professor at Washington University School of Medicine who is leading the project, said in a press release.

“The cognitive issues you see in people exposed to manganese are very similar to mild cognitive impairment and dementia in Parkinson’s disease. Understanding the causes of these cognitive issues is going to be very helpful in ultimately finding better treatments for people exposed to manganese and people with dementia linked to Parkinson’s,” Criswell added.

Funded by the National Institute of Environmental Health Sciences of the National Institutes of Health, the project focuses on welders, who are often exposed to high amounts of manganese through fumes they inhale as part of their job. Previous research by Criswell and colleagues has shown that welders with higher manganese exposure tend to have more Parkinson’s-like symptoms.

“When we do screenings with welders, we always find some with very mild symptoms that only a trained neurologist would detect,” Criswell said. “But their symptoms can worsen over time, and that progression does seem to be related to the amount of manganese exposure. The welders … could yield real insight into how the disease develops and how we can stop it.”

Some 60 welders working in the Midwest are undergoing a series of cognitive tests, as well as a positron emission tomography (PET) brain scan. This scan can assess the health of two types of neurons: those that produce dopamine (dopaminergic neurons), and those that produce acetylcholine (cholinergic neurons).

While the involvement of dopaminergic neurons in manganism is well established, little is known about the role of cholinergic neurons.

Because these two neuron types are located close together in the brain, Criswell and other researchers believe that they could be involved, too. Namely, the researchers think that damage to cholinergic neurons may account for some of the cognitive issues not explained by damage to dopaminergic neurons.

By studying the brains of these welders, the project could shed light on the underlying neurology of manganism. Since the conditions are so similar, these insights may also help in better understanding — and, eventually, finding ways to better treat — Parkinson’s disease.