APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

Abstract

Background Continuing 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. Methods We 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. Results An interquartile range (IQR: 14.23 μg/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. Conclusions Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis

“…Our results also support the link of Pb with cognitive domains of processing speed, sustained attention, and working memory (DSST) and to a lesser degree for composite cognitive score. We note that published evidence suggests strong links between Pb and various measures of later-life cognitive performance, such as with cognitive decline (16,18,19,55), eye-hand coordination (56), executive functioning, and verbal memory and learning (56,57). In bringing these individual pathways together in mediation analysis, we demonstrated that 4% of racial disparities in DSST score was mediated through higher patella Pb among Black participants vs. White participants.…”

“…The etiologic window encompassing initiation of physiological processes and accumulation of damage leading to abnormal cognitive decline is thought to span years to decades (2,12). Epidemiological evidence consistently and robustly links environmental Pb to accelerated cognitive aging, poorer laterlife cognitive function, AD diagnosis and AD-related mortality (12,16,17,18,19). Due to historic and continuing trends of systemic environmental injustice and segregation in the U.S. driving poverty and deteriorating housing and water infrastructure, racial disparities of higher yet avoidable Pb exposure have been tracked since the 1970s and persist currently (11).…”

Lead Exposure and Alzheimer’s Disease Mortality Among US Adults: NHANES Analysis from 1988-2008

“…(2016) only found such an association in individuals with apolipoprotein E (APOE) ε4ε4 genotypes 37,39 . It should be emphasized that while cognitive impairment may sometimes be a precursor of AD, this is not invariably so 40 .…”

Modifying effects of education on the association between lifestyle behaviors and the risk of obesity: evidence from South Korea

“…Unfortunately, no study to date has performed a multi-dimensional analysis of the associations between lifestyle behaviors and education in relation to obesity. This lack leaves studies of obesity far behind those of other health outcomes or of risk factors in exploring the interplay between or among various influencing factors [ 13 , 14 ], and may also be a barrier to developing theories and designing appropriate policies for reducing obesity.…”