ArticleEnvironmental research2016
APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals.
Article in Environmental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure.Environmental science and pollution research international · 2022Pooled it
- Air Pollution and Dementia: A Systematic Review.Journal of Alzheimer's disease : JAD · 2019Pooled it
- Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.BMC neurology · 2026Article
- Association of midlife air pollution and road proximity exposure with 29-year cognitive decline.Neurotoxicology · 2025Article
- Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis.American journal of epidemiology · 2025Article
- Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.JAMA network open · 2024Article
- Toxic Metals Exposure and APOE4 Gene Variant in Cognitive Decline Disorders.Archives of Razi Institute · 2022Review
- Low-level Lead Exposure Impairs Fronto-executive Functions: A Call to Update the DSM-5 with Lead Poisoning as a Neurodevelopmental Disorder.Psychology & neuroscience · 2020Article
- Modifying effects of education on the association between lifestyle behaviors and the risk of obesity: evidence from South Korea.BMC public health · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundContinuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied.
methodsWe determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test.
resultsAn interquartile range (IQR:14.23μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: -0.11 to -0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: -0.97 to -0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: -0.11, 95%CI: -0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele.
conclusionsOur findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.