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Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife

Research output: Contribution to journalArticle

Original languageEnglish
JournalJAMA : the journal of the American Medical Association
Accepted/In press22 Sep 2020

Bibliographical note

First authors are Aaron Reuben and Maxwell Elliott

King's Authors

Abstract

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

Objective. 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).

Exposure. Childhood blood-lead levels measured at age 11 years.

Main Outcomes and Measures. Structural brain integrity at age 45 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)-100(diffusion is perfectly anisotropic)]), and 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). Age-45 cognitive function was assessed objectively via the Wechsler Adult Intelligence Scale–IV [IQ range, 40-160, standardized to mean(SD)=100(15)] and subjectively via informant and self-reports [z-score units, scale mean(SD)=0(1)].

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

Conclusion 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 mid-life. Because of the large number of statistical comparisons, some findings may represent type I error.

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