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

Abstract

BACKGROUND AND AIM: Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. This study tested the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. METHODS: Hypotheses tested in the Dunedin Study, a New Zealand-based population-representative 1972-1973 birth cohort (N=564 analytic sample) followed to age 45 years. Childhood blood-lead levels measured at age 11 years were combined with MRI-measures of brain integrity at age 45 years, including gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy), and brainAGE, a composite index of the gap between chronological age and a machine-learning algorithm-estimated brain age. Age-45 cognitive function was also assessed, objectively via the Wechsler Adult Intelligence Scale–IV and subjectively via informant and self-reports. RESULTS: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). CONCLUSIONS:In this four-decade study, higher childhood blood-lead level was associated with lower structural brain integrity in midlife. Childhood lead exposure may have long-term consequences for adult brain health. KEYWORDS: Heavy metals, Neurodegenerative outcomes, Environmental epidemiology