Effects of childhood lead exposure on the brain seen in midlife


A new investigation reports on the long-term effect of lead exposure found in brain imaging of midlife adults.

No safe level of exposure to lead exists, which is the reason for the intensive removal of the substance from older buildings where it’s in the paint, the pipes that bring water from water sources, and even attempts to remove the lead that sits on roadsides as a result of leaded gasoline. One of the worst effects of lead exposure in a child is the impact that it has on the child’s brain. A report in JAMA provides further evidence of this danger by looking at magnetic resonance imaging (MRI) in adults.1

The researchers used the Dunedin Study, which included a population-representative 1972-1973 birth cohort in New Zealand, and followed those participants until age 45 tears. They used MRIs to look at the structural brain integrity of each participant at age 45 years, which included 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), which is a composite index of the gap between a matching learning algorithm-estimated brain age and the participant’s chronological age with an 0 representing a brain age equivalent to the chronological age and positive and negative values representing older and younger brain ages. The Wechsler Adult Intelligence Scale IV was used to assess each participant’s cognitive function.

There were 997 participants in the cohort who reached their 45th birthday and 564 of those participants underwent lead testing when they were aged 11 years. The average blood lead level at 11 years of age was 10.99 μg/dL. When the researchers adjusted for all covariates, they found that each increase of 5-μg/dL in the childhood blood level was significantly linked to 1.19-cm2 smaller cortical surface area (95% CI, −2.35 to −0.02 cm2; P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, −0.17 to −0.03 cm3; P = .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. Additionally, each 5-μg/dL increase in the childhood blood lead level had a significant tie with a 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). However, the researchers found no statistically significant link between childhood blood lead levels and self-reported cognitive problems (b = −0.02 points; 95% CI, −0.10 to 0.07; P = .68) or blood lead levels and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, −0.02 to 0.13 log mm3; P = .17) or mean cortical thickness (b = −0.004 mm; 95% CI, −0.012 to 0.004 mm; P = .39).

The investigators concluded that having a higher blood lead level in childhood was linked to certain differences in some MRI measures of brain structures that would indicate lower structural brain integrity in midlife. They did note that some of the findings could indicate a type I error due to the large number of statistical comparisons.


1. Reuben A, Elliott M, Abraham W. Association of childhood lead exposure with mri measurements of structural brain integrity in midlife. JAMA. 2020;324(19):1970-1979. doi:10.1001/jama.2020.19998

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