Environment/Climate Change
DNA Methylation Biomarkers for Cumulative Lead Exposures and Cognitive Impairment Kanghong Shao* Kanghong Shao Yu Yu Beate Ritz Kimberly C Paul
Background Recent evidence suggests that cumulative low-level lead exposure has adverse effects on cognitive function in the elderly. To date, the few studies that examined it measured bone lead exposure with K-X-ray fluorescence (KXRF), methods that are mostly unavailable in large community-based studies. Here, we explore the use of a methylation measures for bone lead in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.
Methods Tibia and patella bone lead levels were measured using blood DNA methylation biomarkers in 643 participants from the ADNI cohort. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test. Longitudinal analyses of bone lead and cognitive decline were conducted using linear mixed-effect regression models.
Results DNAm derived tibia and patella lead levels were negatively associated with MoCA scores over time. With increasing tibia lead, there was a decrease in MoCA scores (per interquartile range (IQR): β=-0.25; 95%CI: -0.44, -0.05), while the MoCA decrease for patella lead was smaller (per IQR: β=-0.16; 95%CI: -0.38, 0.07). When stratifying by sex, women showed a stronger decrease in cognitive function with increasing tibia lead (per IQR β=-0.35; 95%CI: -0.65, -0.04) than in men (per IQR β=-0.19; 95%CI: -0.44, 0.07). The estimated decrease in MoCA scores per tibia lead IQR increase was strongest among participants with two APOE4 alleles (per IQR β=-0.85; 95%CI: -1.63, -0.08), while for those with one or zero alleles we estimated weaker effect sizes (per IQR one allele: β=-0.27; 95%CI: -0.62, 0.08; zero allele: β=-0.13; 95%CI: -0.37, 0.11).
Conclusion These findings strengthen the evidence that cumulative long-term lead exposures at environmental levels are associated with decreased cognitive function in the elderly, especially women and carriers of two APOE4 alleles. These findings based on whole blood methylation data align well with previous epidemiologic studies that used KXRF for measuring bone lead.