Childhood Lead Exposure Leads to Structural Changes in Middle-Aged Brains

Summary: Elevated levels of lead in the blood of children was associated with structural changes in the brain during mid-life. Those with higher levels of lead exposure as children had decreased hippocampal volume and structural deficits in white-matter integrity.

Source: Duke University

More than three decades after they were found to have elevated blood lead levels as children, a group of middle-aged adults were found to have some small but significant changes in brain structure that corresponded to their dose of lead exposure in early life.

MRI scans at age 45 revealed some small but significant changes in the brains of the people who had higher lead exposures measured at age 11.

For each 5 micrograms per deciliter more lead they carried as children, the study participants lost an average of 2 IQ points by age 45. They also had slightly more than 1 square centimeter less cortical surface area and 0.1 cubic centimeter less volume in the hippocampus, which plays a role in memory, learning and emotions.

Participants with the highest childhood lead exposures also demonstrated structural deficits in the integrity of their brains’ white matter, which is responsible for communication between brain regions.

The research participants themselves reported no loss of cognitive abilities, but people close to them said otherwise, noting that they tended to display small everyday problems with memory and attention, such as getting distracted or misplacing items.

“We find that there are deficits and differences in the overall structure of the brain that are apparent decades after exposure,” said Duke University doctoral candidate Aaron Reuben, who is a co-first author on the study, which appears Nov. 17 in the Journal of the American Medical Association. “And that’s important because it helps us understand that people don’t seem to recover fully from childhood lead exposure and may, in fact, experience greater problems over time.”

“All of our brain measures were selected based on previous associations with age-related decline and cognition,” said Duke doctoral candidate Maxwell Elliott, co-first author of the study. “Cortical surface area has one of the strongest relationships with cognitive functioning.”

The findings come from a long-term study of more than 1,000 people born in the same town in New Zealand in 1972 and 1973 who have been studied nearly continuously since. For this study, the researchers had childhood lead exposure data for 564 of the study participants, who grew up during the peak era of leaded gasoline, which ran from the late-1960’s to the late-1980s. As was true across the developed world during that time, almost all of the study participants were exposed to higher lead levels than are permitted today.

“Our findings involve gross features of how your brain looks as a whole,” explained Terrie Moffitt, the Nannerl O. Keohane distinguished professor of psychology & neuroscience at Duke and senior author on the paper. “Our research started by looking at these features of the brain because scientists don’t really know a whole lot about childhood lead exposure and the brain later in life.”

This shows two heads
Participants with the highest childhood lead exposures also demonstrated structural deficits in the integrity of their brains’ white matter, which is responsible for communication between brain regions. Image is in the public domain

But the differences are there. Elliott said they may reflect long-term consequences of lead exposure, since the cortical surface area, hippocampal volume and white matter structure all grow during childhood and peak in early adulthood.

“More differences may emerge as these people age,” Reuben said.

It’s probably too soon to tell with this well-studied group of middle-aged New Zealanders, but what Reuben would eventually like to understand is whether individuals exposed to lead in childhood may be at greater risk for degenerative disease as they enter older age.

Animal studies have shown that early exposure to lead may lead to brain changes that contribute to degeneration, such as different gene expression patterns and poorer vascular health. But this hasn’t been shown yet in humans, Reuben said.

Funding: Support for the study came from the US National Institute on Aging, the UK Medical Research Council, the US National Institute of Environmental Health Sciences, and the US National Science Foundation. (R01-AG032282, R01-AG049789, MR/P005918/1, F31ES029358, DGE-1644868) and the New Zealand Health Research Council, and New Zealand Ministry of Business, Innovation and Employment.

About this neuroscience research news

Source: Duke University
Contact: Karl Leif Bates – Duke University
Image: The image is in the public domain

Original Research: Closed access.
Association of Childhood Lead Exposure with MRI Measurements of Structural Brain Integrity in Midlife” by Aaron Reuben, Maxwell Elliott, Wickliffe C. Abraham, Jonathan Broadbent, Renate Houts, David Ireland, Annchen Knodt, Richie Poulton, Sandhya Ramrakha, Ahmad Hariri, Avshalom Caspi and Terrie E. Moffitt. JAMA


Association of Childhood Lead Exposure with MRI Measurements of Structural Brain Integrity in Midlife


Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown.


To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife.

Design, Setting, and Participants  

The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N = 564 analytic sample) to age 45 years (until April 2019).


Childhood blood lead levels measured at age 11 years.

Main Outcomes and Measures  

Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm–estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1]).


Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, −2.35 to −0.02 cm2P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, −0.17 to −0.03 cm3P = .006), lower global fractional anisotropy (b = −0.12; 95% CI, −0.24 to −0.01; P = .04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P = .05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, −0.02 to 0.13 log mm3P = .17) or mean cortical thickness (b = −0.004 mm; 95% CI, −0.012 to 0.004 mm; P = .39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, −3.39 to −0.74; P = .002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P = .03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b = −0.02 points; 95% CI, −0.10 to 0.07; P = .68).

Conclusions and Relevance  

In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.

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