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

Publication ,  Journal Article
Reuben, A; Elliott, ML; Abraham, WC; Broadbent, J; Houts, RM; Ireland, D; Knodt, AR; Poulton, R; Ramrakha, S; Hariri, AR; Caspi, A; Moffitt, TE
Published in: JAMA
November 2020

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.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.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 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. 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 mm3; P = .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).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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Published In

JAMA

DOI

EISSN

1538-3598

ISSN

0098-7484

Publication Date

November 2020

Volume

324

Issue

19

Start / End Page

1970 / 1979

Related Subject Headings

  • Wechsler Scales
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Machine Learning
  • Longitudinal Studies
  • Lead
  • Humans
  • General & Internal Medicine
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Reuben, A., Elliott, M. L., Abraham, W. C., Broadbent, J., Houts, R. M., Ireland, D., … Moffitt, T. E. (2020). Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife. JAMA, 324(19), 1970–1979. https://doi.org/10.1001/jama.2020.19998
Reuben, Aaron, Maxwell L. Elliott, Wickliffe C. Abraham, Jonathan Broadbent, Renate M. Houts, David Ireland, Annchen R. Knodt, et al. “Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife.JAMA 324, no. 19 (November 2020): 1970–79. https://doi.org/10.1001/jama.2020.19998.
Reuben A, Elliott ML, Abraham WC, Broadbent J, Houts RM, Ireland D, et al. Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife. JAMA. 2020 Nov;324(19):1970–9.
Reuben, Aaron, et al. “Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife.JAMA, vol. 324, no. 19, Nov. 2020, pp. 1970–79. Epmc, doi:10.1001/jama.2020.19998.
Reuben A, Elliott ML, Abraham WC, Broadbent J, Houts RM, Ireland D, Knodt AR, Poulton R, Ramrakha S, Hariri AR, Caspi A, Moffitt TE. Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife. JAMA. 2020 Nov;324(19):1970–1979.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

ISSN

0098-7484

Publication Date

November 2020

Volume

324

Issue

19

Start / End Page

1970 / 1979

Related Subject Headings

  • Wechsler Scales
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Machine Learning
  • Longitudinal Studies
  • Lead
  • Humans
  • General & Internal Medicine
  • Female