Dataset Information

APOE ?4 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?g/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 ?4 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 ?4 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 ?4 allele. CONCLUSIONS:Our findings suggest that individuals carrying both ?4 alleles are more susceptible to lead impact on global cognitive decline during aging.

SUBMITTER: Prada D

PROVIDER: S-EPMC5071136 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Prada Diddier D Colicino Elena E Power Melinda C MC Weisskopf Marc G MG Zhong Jia J Hou Lifang L Spiro Avron A Vokonas Pantel P Brenan Kasey K Herrera Luis A LA Schwartz Joel J Wright Robert R Hu Howard H Baccarelli Andrea A AA

Environmental research 20160727

<h4>Background</h4>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.<h4>Methods</h4>We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-re ...[more]

PMID: 27474937

Similar Datasets

Project description:BackgroundThere is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele.ObjectivesWe assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors.MethodsThe Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18-24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends.ResultsAmong 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI -0.1, -0.06) in global cognition across biennial visits among APOE-ε4 positive individuals and a 0.07 SD (95%CI -0.09, -0.05) decline among APOE-ε4 negative individuals. Results for PM2.5, PM10 and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants.ConclusionsThese results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.

Project description:BackgroundChronic exposure to particulate air pollution may accelerate cognitive decline in older adults, although data on this association are limited. Our objective was to examine long-term exposure to particulate matter (PM) air pollution, both coarse ([PM 2.5-10 μm in diameter [PM(2.5-10)]) and fine (PM <2.5 μm in diameter [PM(2.5)]), in relation to cognitive decline.MethodsThe study population comprised the Nurses' Health Study Cognitive Cohort, which included 19,409 US women aged 70 to 81 years. We used geographic information system-based spatiotemporal smoothing models to estimate recent (1 month) and long-term (7-14 years) exposures to PM(2.5-10), and PM(2.5) preceding baseline cognitive testing (1995-2001) of participants residing in the contiguous United States. We used generalized estimating equation regression to estimate differences in the rate of cognitive decline across levels of PM(2.5-10) and PM(2.5) exposures. The main outcome measure was cognition, via validated telephone assessments, administered 3 times at approximately 2-year intervals, including tests of general cognition, verbal memory, category fluency, working memory, and attention.ResultsHigher levels of long-term exposure to both PM(2.5-10) and PM(2.5) were associated with significantly faster cognitive decline. Two-year decline on a global score was 0.020 (95% CI, -0.032 to -0.008) standard units worse per 10 μg/m(3) increment in PM(2.5-10) exposure and 0.018 (95% CI, -0.035 to -0.002) units worse per 10 μg/m(3) increment in PM(2.5) exposure. These differences in cognitive trajectory were similar to those between women in our cohort who were approximately 2 years apart in age, indicating that the effect of a 10-μg/m(3) increment in long-term PM exposure is cognitively equivalent to aging by approximately 2 years.ConclusionLong-term exposure to PM(2.5-10) and PM(2.5) at levels typically experienced by many individuals in the United States is associated with significantly worse cognitive decline in older women.

Project description:ObjectiveAn Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ?4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE.MethodsParticipants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ?4 alleles and either a high or low g-score: APOE ?4-/low g-score; APOE ?4-/high g-score; APOE ?4+/low g-score; and APOE ?4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE.ResultsIndividuals in the APOE ?4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ?4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons.ConclusionsIndividuals with multiple AD risk genes in addition to having one or more APOE ?4 alleles are at greater risk of cognitive decline than individuals with either APOE ?4 or a high genetic risk score. Among those with one or more APOE ?4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.

Dataset Information

APOE ?4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets