Functional MRI Shows Permanent Brain Damage From Lead Poisoning in Early Childhood

Fran Lowry

December 07, 2009

December 7, 2009 (Chicago, Illinois) — New research using functional magnetic resonance imaging (MRI) to evaluate brain function has found that adults who were exposed to lead as young children incur permanent brain injury.

The results, which were presented here at the Radiological Society of North America 95th Scientific Assembly and Annual Meeting, should challenge the notions that the damage from lead poisoning reverses as children grow into adulthood and that their blood lead levels decrease over time.

"Seeing is believing," said lead author Kim Cecil, PhD, imaging scientist at Cincinnati Children's Hospital Medical Center and professor of radiology, pediatrics and neuroscience at the University of Cincinnati College of Medicine in Ohio. "We really didn't know that the deficits persisted into adulthood. For the first time, functional MRI has allowed us to really show what structures in the brain are being affected by lead poisoning."

Lead exposure has been linked to diminished IQ, poor academic performance, inability to focus, and increased criminality, Dr. Cecil said.

The study involved 42 adults (20 females, 22 males; mean age, 21 years) who were part of the Cincinnati Lead Study, a long-term lead exposure study that examined prenatal and early childhood lead exposure in 376 infants between 1979 and 1984.

The study participants were all from depressed socioeconomic areas in Cincinnati, which were historically known for lead poisoning. Nearly all were African American, and the mean blood lead level was 14 µg/dL. The US Centers for Disease Control and Prevention has set 10 µg/dL as the action level for response, Dr. Cecil noted.

Now grown up, the subjects agreed to undergo functional MRI while performing 2 tasks — an attention task and an impulsivity, or Go/No-Go, task — to measure their executive functioning ability.

The attention task, completed by 33 subjects, was a continuous performance task. It involved pressing a button when identical numbers appeared on a screen. Twenty-six subjects completed a Go/No-Go task to test their impulsivity. This involved pressing a button when a blue X appeared on the screen and not pressing a button when a red X appeared.

Increased mean blood lead levels were associated with decreased circuit activity in posterior portions of the parietal cortex, including the bilateral precuneus and posterior cingulate.

Decreased activation was also observed in the right insula, left superior temporal gyrus, and in the hippocampal complex, Dr. Cecil reported.

Interestingly, men, who had the greatest amount of brain damage, used other areas of the brain, including the anterior portion of the cingula and the middle part of the frontal lobe. These areas are not usually used for these tasks, Dr. Cecil explained.

"It was a surprise to us to discover that men's brains and women's brains were so different, despite equivalent lead exposure. The men appeared to be compensating for the loss of their executive function, which is governed by the frontal lobe," she said.

"We speculate that estrogen might have some protective effect. This has been seen in animal studies of lead exposure," Dr. Cecil told Medscape Radiology. "When researchers dose animals with lead, the females seem to be protected, compared with the males. This is consistent with our observations that the men's brains had greater decrements, greater loss of activity, according to their levels of blood lead. They also had greater amounts of compensation by recruiting additional areas in the brain."

In fact, most of the study findings were driven by the results in men.

"When we did the analysis, the women actually were not presenting significant results. Most of this study's findings are being driven by the men," she noted. "We are starting to see this clinically in criminality studies. Men with significant lead exposure are much more likely to be involved in criminal activity," Dr. Cecil said.

She told Medscape Radiology that we might have become too complacent about lead poisoning. She hopes that this study will increase awareness of the problem and even spur some efforts to rid the environment of the threat of lead poisoning.

"Even though we are a global society, there are many countries, according to the World Health Organization, that are still using leaded gasoline. As well, products are being imported from China that are made with lead," she said.

"Even in Washington, DC, when the water-treatment facilities changed their chlorination process, they used a product that was leaching lead from all the old sewer and household pipes. Pediatricians in certain regions saw a spike in the instances of elevated blood lead levels in children."

Robert D. Zimmerman, MD, executive vice-chair in the Department of Radiology at Weil Cornell Medical College and the director of diagnostic imaging at New York Presbyterian Hospital in New York City, was invited to comment on this study by Medscape Radiology. He said the study shows the power of these newer techniques, such as functional MRI, to document subtle changes in brain structure and function that clinicians suspected but could not be sure of.

"Dr. Cecil says that seeing is believing, and I think human beings are very visual animals, so even though there are all kinds of psychometric testing that would probably shows that these are not particularly surprising findings, the fact that you can see them on an imaging study makes it more powerful," he said.

Being able to visualize the deficits also facilitates the study of these patients over time and helps to determine whether interventions can be useful.

"On one level, you do imaging to learn about the science; on another level, you hope that the information from these studies will lead to treatments and to a way to track whether the treatments are effective."

He added: "This is a fascinating study and it shows the level of information we can gather using these new techniques."

The study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. Dr. Cecil and Dr. Zimmerman have reported no relevant financial conflicts of interest.

Radiological Society of North America (RSNA) 95th Scientific Assembly and Annual Meeting: Abstract SSJ16-06. Presented December 1, 2009.


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