Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older

Liu, Huan; Su, Liqin; Chen, Xi; Wang, Sisi; Cheng, Yibin; Lin, Shaobin; Ding, Liang; Liu, Jingyi; Chen, Chen; Unverzagt, Frederick W.; Hake, Ann Marie; Jin, Yinlong; Gao, Sujuan

doi:10.1016/j.scitotenv.2020.144072

Cited by 27 publications

(15 citation statements)

References 39 publications

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“…Previous studies have reported that cadmium exposure was associated with dysfunction in perception and memory. 68 , 69 Supporting our study, a growing body of evidence showed that an increased prevalence of age-related diseases is associated with cadmium. 70 , 71 It is reported that cadmium can damage mitochondria and promote the peroxidation of cellular lipids in the parietal cortex, resulting in damage to the structure and function of neuronal cell membranes.…”

Section: Discussionsupporting

confidence: 82%

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis

Xiao

Cheng

Cai

et al. 2022

Environ Health Perspect

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Background: Exposure to heavy metals has been reported to be associated with multiple diseases. However, direct associations and potential mechanisms of heavy metals with physical disability remain unclear. Objectives: We aimed to quantify associations of heavy metals with physical disability and further explore the potential mechanisms of DNA methylation on the genome scale. Methods: A cross-sectional study of 4,391 older adults was conducted and activities of daily living (ADL) disability were identified using a 14-item scale questionnaire including basic and instrumental activities to assess the presence of disability (yes or no) rated on a scale of dependence. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated to quantify associations between heavy metals and ADL disability prevalence using multivariate logistic regression and Bayesian kernel machine regression (BKMR) models. Whole blood–derived DNA methylation was measured using the HumanMethylationEPIC BeadChip array. An ADL disability-related epigenome-wide DNA methylation association study (EWAS) was performed among 212 sex-matched ADL disability cases and controls, and mediation analysis was further applied to explore potential mediators of DNA methylation. Results: Each 1-standard deviation (SD) higher difference in -transformed manganese, copper, arsenic, and cadmium level was significantly associated with a 14% (95% CI: 1.05, 1.24), 16% (95% CI:1.07, 1.26), 22% (95% CI:1.13, 1.33), and 15% (95% CI:1.06, 1.26) higher odds of ADL disability, which remained significant in the multiple-metal and BKMR models. A total of 85 differential DNA methylation sites were identified to be associated with ADL disability prevalence, among which methylation level at cg220000984 and cg23012519 (annotated to IRGM and PKP3 ) mediated 31.0% and 31.2% of manganese-associated ADL disability prevalence, cg06723863 (annotated to ESRP2 ) mediated 32.4% of copper-associated ADL disability prevalence, cg24433124 (nearest to IER3 ) mediated 15.8% of arsenic-associated ADL disability prevalence, and cg07905190 and cg17485717 (annotated to FREM1 and TCP11L1 ) mediated 21.5% and 30.5% of cadmium-associated ADL disability prevalence (all ). Discussion: Our findings suggested that heavy metals contributed to higher prevalence of ADL disability and that locus-specific DNA methylation are partial mediators, providing potential biomarkers for further cellular mechanism studies. https://doi.org/10.1289/EHP10602

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Section: Discussionsupporting

confidence: 82%

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis

Xiao

Cheng

Cai

et al. 2022

Environ Health Perspect

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“…Studies using NHANES data show that increased blood cadmium is associated with worse cognitive function in adults aged 60 years or older [37,38]. Similarly, a study conducted in Chinese adults aged 65 or older also report that higher cadmium exposure is associated with greater cognitive decline [11]. However, the Health Outcomes and Measures of the Environment study, which measure maternal urinary cadmium concentrations at 26 weeks of gestation and assess cognitive function of children at ages 1, 2, 3, 4, 5, and 8 years, its result show no signi cant association between maternal cadmium exposure and cognitive function of children [39].…”

Section: Discussionmentioning

confidence: 99%

The association between cadmium exposure and axonal injury biomarker, serum neurofilament light chain levels in US adults

Luo,

Lin

2024

Preprint

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Background and Aims: Cadmium exposure has been shown a toxic effect on the nervous system, but little is known regarding the link between cadmium exposure and axonal injury. Therefore, we aim to investigate whether there is a relationship between blood cadmium and serum neurofilament light chain (NfL) levels in the general population. Methods and Results: In the National Health and Nutrition Examination Survey 2013–2014, 1,040 participants with a median (IQR) age of 47 (35–60) years are enrolled. Serum NfL levels are measured using a highly sensitive immunoassay. Whole blood cadmium concentrations are detected using inductively coupled plasma mass spectrometry. Linear regression and restricted cubic spline models are used to analyze the strength and shape of the relationship between blood cadmium and serum NfL levels. In full adjusted model, blood cadmium levels are positively associated with serum NfL levels (Q4 vs Q1, β = 3.35, 95%CI: 0.41, 6.30, p for trend = 0.014). A potential linear positive dose-effect relationship is found between blood cadmium and serum NfL levels (p for non-linearity = 0.15), and the potential threshold dose of blood cadmium is 0.7 µg/L. The stratified analysis shows a significant positive relationship between blood cadmium and serum NfL levels is limited to middle-aged and older adults. Conclusion: The present study suggests a positive association between blood cadmium and serum NfL levels in the general US population. This study is expected to provide new ideas for the primary prevention and mechanism exploration of neurodegenerative diseases.

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“…The different results may be caused by the control of different confounders, the different study designs used, or the different effects of cadmium in the research design. In addition, the findings of a prospective cohort study in southwestern and eastern China suggested that higher cadmium exposure was associated with greater cognitive decline in Chinese adults aged 65 years or older [ 31 ]. The negative correlation between blood cadmium and cognitive performance was of great significance for proposing strategies to delay the decline of cognitive performance in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Interaction between ω-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011–2014

Huang

Ren

2022

BMC Geriatr

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Background Identifying preventable diets and environmental exposure is essential to ensuring the health of the aging population. This study evaluated the interaction effect between blood cadmium and ω-6 fatty acids intake on low cognitive performance in Americans. Method The data of this cross-sectional study were obtained from the 2011–2012 and 2013–2014 National Health and Nutritional Examination Survey (NHANES). Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer’s Disease test, Animal Fluency Test, and Digit Symbol Substitution Test. Multivariate logistic regression models were used. Results A total of 1,918 individuals were included, with 467 (24.35%) low cognitive performance. Compared with participants with normal-level blood cadmium, those with high-level blood cadmium had a higher risk of low cognitive performance [odds ratio (OR) was 1.558 with 95% confidence interval (CI): 1.144–2.123]. Low-level ω-6 fatty acids intake was positively associated with low cognitive performance [OR = 1.633 (95%CI: 1.094–2.436)] compared with normal-level intake. Moreover, there was a significant interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on the risk of low cognitive performance (relative excess risk due to interaction: 0.570, 95%CI: 0.208-0.932; the attributable proportion of interaction: 0.219, 95%CI: 0.102‐0.336; synergy index: 1.552, 95%CI: 1.189‐2.027). Conclusions There was a synergistic interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on low cognitive performance. Low-level ω-6 fatty acids intake may amplify the adverse effects of long-term exposure to cadmium on cognitive performance. This may have a certain significance for the prevention of cognitive decline in the elderly.

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Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older

Cited by 27 publications

References 39 publications

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis

The association between cadmium exposure and axonal injury biomarker, serum neurofilament light chain levels in US adults

Interaction between ω-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011–2014

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