Does lead exposure cause decreased brain size?

ResearchBlogging.orgA recently published study seems to indicate that adult brain volume is reduced in individuals with significant lead exposure during childhood. While this study may lead to important findings linking lead to reduced cognitive function, it is important to note that observed effect is very small, very hard to link to specific outcomes, and may not exist. But it is worth a further look.


The study in question is summarized below and, as an Open Access publication, is totally accessible for you to read. The upshot is that individuals who were part of a long term study (also discussed here) showed a negative correlation between early levels of lead exposure and gray mater volume in specific areas of the brain. Since lead exposure is known to be linked to cognitive function impairment, it is possible that these changes in gray matter volume are a clue to the specific nature of that effect.

However .....

People do sometimes get very excited about brain volume and its relation to intelligence, and often get things wrong in this area. So, I'd like to point out a few things to keep in mind when looking at a study like this, to place it in context.

First, it is important to note that the differences observed in this study are very very small. If these were differences in muscle mass, they would not be predictive of athletic performance. If they were differences in profit margin, they would not be predictive of fiscal health of corporations. If they were translated into differences in accuracy of airline flight control systems, the airplanes would still get to their destinations. In other words, this level (amount, magnitude) of difference could be utterly meaningless. It is probably not utterly meaningless, but I just want you to know that we are not speaking big differences.

Second, the strength of the correlation is not impressive. Here is what one part of the data look like:

Figure 2.Regional Brain Volume Loss for the Cincinnati Lead Study Participants. The relationship of individual brain volume with mean childhood blood lead concentrations within a medial frontal cluster is illustrated by this plot. The model is adjusted for age at time of scanning and birth weight, using a cluster threshold of 700 voxels and unadjusted p ⤠0.001.

This is not impressive. It may (or may not) be real, but this correlation would not win you any prizes in the prediction game.

Third, note that the difference is accentuated in males over females, but there is a range of area specific brain volume decreases in males to begin with. It is quite possible that this is a potentiated effect suggesting a more complex relationship than just "more volume = good, less volume = bad." Which is what you were thinking, admit it.

Fourth, do keep in mind that with age gray matter volume decreases in all humans as a function of brain development. A new born baby has many many more neurons than an adult because brains develop by overproducing both neurons and connections, then culling out that which is not appropriate. Brains are not built, up, they are sculpted down. So why is a very small reduction in neural volume not connected with increased rather than decreased capacity? Good question, and one that can not be addressed by this study.

Fifth, overall brain volume which may be correlated with a number of different things that make up brain volume varies widely .... very widely .... with either no clear link to cognitive function or in some cases even a counter intuitive link.

Sixth, and not related to the science but rather the context of the science, brain volume is considered very important mainly by researchers primarily interested in proving previously discredited racial theories about intelligence. It is of some concern that this study would be misused in this way. Watch for it.

The summary text provided with this study is excellent, so I'll excerpt from it here:

...The organ that is most sensitive to lead exposure is the brain, and children's brains are particularly vulnerable because they are still developing. Children who swallow large amounts of lead can develop widespread brain damage that causes convulsions and sometimes death. Children who are repeatedly exposed to low to moderate amounts of lead (e.g., through accidentally swallowing residues of old lead paint or contaminated soil) can develop learning or behavioral problems....

Lead exposure has been linked with various types of brain damage. ... However, we know little about how lead damages the brain in this way and little about which brain regions are affected by exposure to low to moderate levels of lead during childhood. In this study, the researchers wanted to test the possibility that childhood lead exposure might lead to shrinking ("volume loss") parts of the brain, particularly the parts that are crucial to cognition and behavior. They therefore studied the relationship between childhood lead exposure and adult brain volume. ...

...The researchers found that exposure to lead as a child was linked with brain volume loss in adulthood, particularly in men. There was a "dose-response" effect--in other words, the greatest brain volume loss was seen in participants with the greatest lead exposure in childhood. The brain volume loss was most noticeable in a part of the brain called the prefrontal cortex--especially a region called the "anterior cingulate cortex." When they examined the relationship between brain volume and measures of brain functioning, they found a link between brain volume and fine motor control, but not with the other measures. ...

Cecil, K.M., Brubaker, C.J., Adler, C.M., Dietrich, K.N., Altaye, M., Egelhoff, J.C., Wessel, S., Elangovan, I., Hornung, R., Jarvis, K., Lanphear, B.P., Balmes, J. (2008). Decreased Brain Volume in Adults with Childhood Lead Exposure. PLoS Medicine, 5(5), e112. DOI: 10.1371/journal.pmed.0050112


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Ahh, the memories of childhood. This reminds me of the scores of times I wandered into the kitchen to find my father at the stove, cooking ... with a propane torch to speed up the process. What was he cooking? Lead. He was melting lead in our kitchen, a process which kicked up an odd metallic smell which filled the whole house.

May I ask, why was he cooking lead? I was born after lead poisoning was widely known, so I don't know what you would want to cook lead for. Just curious.

Mr Laden,

Good points about the limitations of volumetric brain studies - it's hard to know what small volumetric differences mean. The paper I am waiting for from this group has to do with the following quote from the paper near the end:

"Future studies with diffusion tensor imaging are needed to evaluate axonal and myelin integrity, since this method reveals quantitative information about the diffusion of water molecules about the myelin sheath of axons (see review [47])."

I talked with a young doctor from the Cinci group (can't remember which author) at the Society for Neuroscience conference last year in San Diego. He presented a poster on the same cohort studied here having undergone diffusion tensor imaging - trying to see if axon/myelin integrity of deep white matter fibers (the main "wires" in the brain) has been compromised. From what I remember the overall regression chart they had on that data set was much better looking: more lead = lower diffusion anisotropy [meaning that either there were fewer axons per volume or myelin (the wire's insulation) is degraded or something like that]. The only problem was that the Cinci group had tried to analyze the data using the same technique they used in this paper a 3D deformation technique (VBM) that doesn't work so hot in white matter [a bunch of people were giving him a hard time about it].

So hopefully this promising data will be turned into a paper soon because it's interpretation is more straightforward (and the data seemed better than the one above) and maybe gives us a lead on one mechanism for lead bad effects.

By Tim Herron (not verified) on 24 Jul 2008 #permalink