Childhood Lead Exposure and Adult Neurodegenerative Disease

Reuben, Aaron

doi:10.3233/jad-180267

Cited by 88 publications

(62 citation statements)

References 241 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Past studies of fluoride-exposed workers suggest possible neurotoxicity, but recent evidence rather points to possible accelerated aging in fluoride-exposed adults [80–82]. As has been proposed for other developmental neurotoxicity [134, 149], early-life exposure to fluoride deserves to be examined in regard to its possible impact on the risk of adult neurodegenerative disease.…”

Section: Plausibility and Implicationsmentioning

confidence: 99%

Developmental fluoride neurotoxicity: an updated review

Grandjean

2019

Environ Health

139

View full text Add to dashboard Cite

Background: After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain. Method: An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012. Results: Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children's performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water. Conclusion: The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.

show abstract

Section: Plausibility and Implicationsmentioning

confidence: 99%

Developmental fluoride neurotoxicity: an updated review

Grandjean

2019

Environ Health

139

View full text Add to dashboard Cite

show abstract

“…Early life Pb exposure also increases the risk for developing a variety of adverse health outcomes later in life, including Alzheimer disease, attention-deficit hyperactivity disorder, cardiovascular disease, and intellectual deficits. [1][2][3][4][5] The Institute for Health Metrics and Evaluation (IHME) estimated in 2017 that Pb exposure accounted for almost 2% of total all-cause mortality and at least 2.5 million years of healthy life lost (disability-adjusted life years [DALYs]) worldwide due to idiopathic developmental intellectual disability, 6 but this may be an underestimate. 7 The health effects of prenatal Pb exposure can be framed with the Developmental Origins of Health and Disease (DoHAD) theory, 8 which links early-life exposures to the development of disease and adverse health effects later in life.…”

Section: Introductionmentioning

confidence: 99%

Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth

et al. 2020

View full text Add to dashboard Cite

Gestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbilical cord blood (UCB) leukocytes. Eighty-nine mother-child dyads from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) longitudinal birth cohorts with available UCB samples were selected for DNA methylation analysis via the Infinium Methylation EPIC BeadChip, which quantifies methylation at >850 000 CpG sites. Maternal blood lead levels (BLLs) during each trimester (T1: 6.56 ± 5.35 µg/dL; T2: 5.93 ± 5.00 µg/dL; T3: 6.09 ± 4.51 µg/dL), bone Pb (patella: 11.8 ± 9.25 µg/g; tibia: 11.8 ± 6.73 µg/g), a measure of cumulative Pb exposure, and UCB Pb (4.86 ± 3.74 µg/dL) were measured. After quality control screening, data from 786 024 CpG sites were used to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by Pb biomarkers using separate linear regression models, controlling for sex and estimated UCB cell-type proportions. We identified 3 DMPs associated with maternal T1 BLL, 2 with T3 BLL, and 2 with tibia bone Pb. We identified one DMR within PDGFRL associated with T1 BLL, one located at chr6:30095136-30095295 with T3 BLL, and one within TRHR with tibia bone Pb (adjusted P-value < .05). Pathway analysis identified 15 overrepresented gene pathways for differential methylation that overlapped among all 3 trimesters with the largest overlap between T1 and T2 (adjusted P-value < .05). Pathways of interest include nodal signaling pathway and neurological system processes. These data provide evidence for differential methylation by prenatal Pb exposure that may be trimester-specific.

show abstract

“… 56 As the generation of lead-exposed individuals age, it is also possible that bone loss during menopause and osteoporosis may result in childhood lead stored in bone being recirculated throughout the body, suggesting the testable hypothesis that the long-term consequences of childhood lead exposure may evolve or expand over time. 57 It is possible that the pediatric challenges of the past may represent emerging concerns for geriatric psychiatry.…”

Section: Discussionmentioning

confidence: 99%