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Association between Copper Exposure and Cognitive Function: A Cross-Sectional Study in a County, Guangxi, China

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Abstract

There has been growing attention to the impact of copper exposure on cognitive function; however, current research on the specific information regarding urinary copper and cognitive function is limited, particularly detailed analyses in the Chinese adult population. This study aimed to explore the association between copper exposure and cognitive function in a cross-sectional design. A total of 2617 participants in a county, Guangxi Zhuang Autonomous Region (Guangxi), China, were included. The mini-mental state examination (MMSE) was used to assess cognitive function, and inductively coupled plasma mass spectrometry was used to measure urinary metal levels. Spearman’s rank correlation was used to analyze the correlation between urinary copper levels and various cognitive function assessment indices. After adjusting for potential confounders, binary logistic regression was used to explore the association between urinary copper levels and the risk of cognitive impairment (CI) as revealed by MMSE, and restricted cubic spline regression was further used to explore the dose-response relationship. The results showed a negative correlation between urinary copper levels and orientation, attention and calculation, memory, language ability, and MMSE total scores (P < 0.05). Compared with the low copper exposure group, the high exposure group showed a 58.5% increased risk of CI (OR = 1.585, 95%CI: 1.125 to 2.235, P = 0.008). A significant linear dose-response relationship was observed between urinary copper levels and the risk of CI (P overall = 0.045, P nonlinearity = 0.081). Our findings suggest that higher copper exposure may be associated with CI in the population of a county, Guangxi, China.

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Data availability

The datasets analyzed during the current study are not publicly available.

References

  1. Taylor-Rowan M, Edwards S, Noel-Storr AH et al (2021) Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome. Cochrane Database Syst Rev 5:CD013540. https://doi.org/10.1002/14651858.CD013540.pub2

    Article  PubMed  Google Scholar 

  2. Jia L, Du Y, Chu L et al (2020) Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Lancet Public Health 5:e661–e671. https://doi.org/10.1016/S2468-2667(20)30185-7

    Article  PubMed  Google Scholar 

  3. Wang J, ** R, Wu Z et al (2022) Moderate increase of serum uric acid within a normal range is associated with improved cognitive function in a non-normotensive population: A nationally representative cohort study. Front Aging Neurosci 14:944341. https://doi.org/10.3389/fnagi.2022.944341

    Article  PubMed  PubMed Central  Google Scholar 

  4. Medhi H, Chowdhury PR, Baruah PD, Bhattacharyya KG (2020) Kinetics of aqueous Cu(II) biosorption onto Thevetia peruviana leaf powder. ACS Omega 5:13489–13502. https://doi.org/10.1021/acsomega.9b04032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pierson H, Yang H, Lutsenko S (2019) Copper transport and disease: what can we learn from organoids? Annu Rev Nutr 39:75–94. https://doi.org/10.1146/annurev-nutr-082018-124242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang Y, Zhou Q, Lu L et al (2023) Copper induces cognitive impairment in mice via modulation of cuproptosis and CREB signaling. Nutrients 15:972. https://doi.org/10.3390/nu15040972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Behzadfar L, Abdollahi M, Sabzevari O et al (2017) Potentiating role of copper on spatial memory deficit induced by beta amyloid and evaluation of mitochondrial function markers in the hippocampus of rats. Met Integr Biometal Sci 9:969–980. https://doi.org/10.1039/c7mt00075h

    Article  CAS  Google Scholar 

  8. Socha K, Klimiuk K, Naliwajko SK, Soroczyńska J, Puścion-Jakubik A, Markiewicz-Żukowska R, Kochanowicz J (2021) Dietary habits, selenium, copper, zinc and total antioxidant status in serum in relation to cognitive functions of patients with Alzheimer’s disease. Nutrients 13:287. https://doi.org/10.3390/nu13020287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Squitti R, Ghidoni R, Simonelli I et al (2018) Copper dyshomeostasis in Wilson disease and Alzheimer’s disease as shown by serum and urine copper indicators. J Trace Elem Med Biol Organ Soc Miner Trace Elem GMS 45:181–188. https://doi.org/10.1016/j.jtemb.2017.11.005

    Article  CAS  Google Scholar 

  10. Wei J, Gianattasio KZ, Bennett EE et al (2022) The associations of dietary copper with cognitive outcomes. Am J Epidemiol 191:1202–1211. https://doi.org/10.1093/aje/kwac040

    Article  PubMed  PubMed Central  Google Scholar 

  11. Agarwal P, Ayton S, Agrawal S et al (2022) Brain copper may protect from cognitive decline and Alzheimer’s disease pathology: a community-based study. Mol Psychiatry 27:4307–4313. https://doi.org/10.1038/s41380-022-01802-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Al-khateeb E, Al-zayadneh E, Al-dalahmah O, Alawadi Z, khatib F, Naffa R, Shafagoj Y (2014) Relation between copper, lipid profile, and cognition in elderly Jordanians. J Alzheimers Dis JAD 41:203–211. https://doi.org/10.3233/JAD-132180

    Article  CAS  PubMed  Google Scholar 

  13. Choe YM, Suh GH, Lee BC, Choi IG, Lee JH, Kim HS, Kim JW (2022) Association between copper and global cognition and the moderating effect of iron. Front Aging Neurosci 14:811117. https://doi.org/10.3389/fnagi.2022.811117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198. https://doi.org/10.1016/0022-3956(75)90026-6

    Article  CAS  PubMed  Google Scholar 

  15. Tombaugh TN, McIntyre NJ (1992) The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 40:922–935. https://doi.org/10.1111/j.1532-5415.1992.tb01992.x

    Article  CAS  PubMed  Google Scholar 

  16. Wongsasuluk P, Chotpantarat S, Siriwong W, Robson M (2021) Human biomarkers associated with low concentrations of arsenic (As) and lead (Pb) in groundwater in agricultural areas of Thailand. Sci Rep 11:13896. https://doi.org/10.1038/s41598-021-93337-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ma J, **e Y, Zhou Y et al (2020) Urinary copper, systemic inflammation, and blood lipid profiles: Wuhan-Zhuhai cohort study. Environ Pollut Barking Essex 1987 267:115647. https://doi.org/10.1016/j.envpol.2020.115647

    Article  CAS  Google Scholar 

  18. Peng Y, Li Z, Yang X et al (2020) Relation between cadmium body burden and cognitive function in older men: A cross-sectional study in China. Chemosphere 250:126535. https://doi.org/10.1016/j.chemosphere.2020.126535

    Article  CAS  PubMed  Google Scholar 

  19. Mo X, Cai J, Lin Y et al (2021) Correlation between urinary contents of some metals and fasting plasma glucose levels: A cross-sectional study in China. Ecotoxicol Environ Saf 228:112976. https://doi.org/10.1016/j.ecoenv.2021.112976

    Article  CAS  PubMed  Google Scholar 

  20. Gou R, Qin J, Pang W et al (2023) Correlation between dietary patterns and cognitive function in older Chinese adults: A representative cross-sectional study. Front Nutr 10:1093456. https://doi.org/10.3389/fnut.2023.1093456

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wei Y, Liu S, Cai J et al (2021) Associations of TFEB gene polymorphisms with cognitive function in rural Chinese population. Front Aging Neurosci 13:757992. https://doi.org/10.3389/fnagi.2021.757992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li H, Jia J, Yang Z (2016) Mini-mental state examination in elderly Chinese: a population-based normative study. J Alzheimers Dis JAD 53:487–496. https://doi.org/10.3233/JAD-160119

    Article  PubMed  Google Scholar 

  23. Sun R, Wang J, Feng J, Cao B (2022) Zinc in cognitive impairment and aging. Biomolecules 12:1000. https://doi.org/10.3390/biom12071000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Brewer GJ (2012) Copper excess, zinc deficiency, and cognition loss in Alzheimer’s disease. BioFactors Oxf Engl 38:107–113. https://doi.org/10.1002/biof.1005

    Article  CAS  Google Scholar 

  25. Chae-Kim J, Patounakis G, Hill MJ (2023) How to deal with confounders in an infertility study? Fertil Steril 119:897–901. https://doi.org/10.1016/j.fertnstert.2023.03.014

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gromadzka G, Tarnacka B, Flaga A, Adamczyk A (2020) Copper dyshomeostasis in neurodegenerative diseases-therapeutic implications. Int J Mol Sci 21:9259. https://doi.org/10.3390/ijms21239259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rozzini L, Lanfranchi F, Pilotto A et al (2018) Serum non-ceruloplasmin non-albumin copper elevation in mild cognitive impairment and dementia due to Alzheimer’s disease: a case control study. J Alzheimers Dis JAD 61:907–912. https://doi.org/10.3233/JAD-170552

    Article  CAS  PubMed  Google Scholar 

  28. Takeuchi H, Taki Y, Nouchi R et al (2019) Association of copper levels in the hair with gray matter volume, mean diffusivity, and cognitive functions. Brain Struct Funct 224:1203–1217. https://doi.org/10.1007/s00429-019-01830-y

    Article  CAS  PubMed  Google Scholar 

  29. Zhou T, Guo J, Zhang J et al (2020) Sex-specific differences in cognitive abilities associated with childhood cadmium and manganese exposures in school-age children: a prospective cohort study. Biol Trace Elem Res 193:89–99. https://doi.org/10.1007/s12011-019-01703-9

    Article  CAS  PubMed  Google Scholar 

  30. Hsu HW, Rodriguez-Ortiz CJ, Lim SL, Zumkehr J, Kilian JG, Vidal J, Kitazawa M (2019) Copper-induced upregulation of MicroRNAs directs the suppression of endothelial LRP1 in Alzheimer’s disease model. Toxicol Sci 170:144–156. https://doi.org/10.1093/toxsci/kfz084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yu H, Jiang X, Lin X et al (2018) Hippocampal subcellular organelle proteomic alteration of copper-treated mice. Toxicol Sci Off J Soc Toxicol 164:250–263. https://doi.org/10.1093/toxsci/kfy082

    Article  CAS  Google Scholar 

  32. Zhao Y-S, Zhang L-H, Yu P-P et al (2018) Ceruloplasmin, a potential therapeutic agent for Alzheimer’s disease. Antioxid Redox Signal 28:1323–1337. https://doi.org/10.1089/ars.2016.6883

    Article  CAS  PubMed  Google Scholar 

  33. Xu J, Church SJ, Patassini S et al (2017) Evidence for widespread, severe brain copper deficiency in Alzheimer’s dementia. Met Integr Biometal Sci 9:1106–1119. https://doi.org/10.1039/c7mt00074j

    Article  CAS  Google Scholar 

  34. Squitti R, Ventriglia M, Simonelli I et al (2021) Copper imbalance in Alzheimer’s disease: meta-analysis of serum, plasma, and brain specimens, and replication study evaluating ATP7B gene variants. Biomolecules 11:960. https://doi.org/10.3390/biom11070960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Squitti R, Faller P, Hureau C, Granzotto A, White AR, Kepp KP (2021) Copper imbalance in Alzheimer’s disease and its link with the amyloid hypothesis: towards a combined clinical, chemical, and genetic etiology. J Alzheimers Dis JAD 83:23–41. https://doi.org/10.3233/JAD-201556

    Article  CAS  PubMed  Google Scholar 

  36. Kepp KP, Squitti R (2019) Copper imbalance in Alzheimer’s disease: Convergence of the chemistry and the clinic. Coord Chem Rev 397:168–187. https://doi.org/10.1016/j.ccr.2019.06.018

    Article  CAS  Google Scholar 

  37. Członkowska A, Litwin T, Dusek P et al (2018) Wilson disease. Nat Rev Dis Primer 4:21. https://doi.org/10.1038/s41572-018-0018-3

    Article  Google Scholar 

  38. Li D-D, Zhang W, Wang Z-Y, Zhao P (2017) Serum copper, zinc, and iron levels in patients with Alzheimer’s disease: a meta-analysis of case-control studies. Front Aging Neurosci 9:300. https://doi.org/10.3389/fnagi.2017.00300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brewer GJ (2014) Alzheimer’s disease causation by copper toxicity and treatment with zinc. Front Aging Neurosci 6:92. https://doi.org/10.3389/fnagi.2014.00092

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhao D, Huang Y, Wang B et al (2023) Dietary intake levels of iron, copper, zinc, and manganese in relation to cognitive function: a cross-sectional study. Nutrients 15:704. https://doi.org/10.3390/nu15030704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang H, Li J, Li Y et al (2022) Sex-specific associations of early postnatal blood copper levels with neurodevelopment at 2 years of age. J Trace Elem Med Biol Organ Soc Miner Trace Elem GMS 74:127072. https://doi.org/10.1016/j.jtemb.2022.127072

    Article  CAS  Google Scholar 

  42. Coelho FC, Squitti R, Ventriglia M et al (2020) Agricultural use of copper and its link to Alzheimer’s disease. Biomolecules 10:897. https://doi.org/10.3390/biom10060897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to all participants, epidemiological investigators, laboratory teams, and collaborators for their invaluable contributions to this study.

Funding

The work was supported by the National Natural Science Foundation of China (Grant Nos. 82260629, 81960583), Major Science and Technology Projects in Guangxi (AA22096026), the Guangxi Natural Science Foundation for Innovation Research Team (2019GXNSFGA245002), Innovation Platform and Talent Plan in Guilin (No. 20220120–2) and Open Project of Key Laboratory of Longevity and Aging-related Diseases (Guangxi Medical University), Ministry of Education (KLLAD202304).

Author information

Author notes

  1. **a Xu, Chunbao Mo, Jian Qin contributed equally to this work.

Authors and Affiliations

  1. Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Shuangyong Road 22, Nanning, 530021, Guangxi, China

    **a Xu, Jian Qin, Qiumei Liu, Xu Tang, Haiying Zhang & Zhiyong Zhang

  2. School of Public Health, Guilin Medical University, Lequn Road 20, Guilin, 541001, Guangxi, China

    Jiansheng Cai & Zhiyong Zhang

  3. School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China

    Chunbao Mo

  4. Guangxi Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, Guangxi, China

    Jiansheng Cai & Zhiyong Zhang

  5. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China

    Jian Qin & Haiying Zhang

  6. Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, Guangxi, China

    Jian Qin

  7. Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China

    Jian Qin

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  1. **a Xu
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Contributions

All authors contributed to the study conception and design. X.X., C.M., J.C., Q.L. and X.T. performed the epidemiological investigation, sample collection, and metal levels detection. X.X. analyzed the data and drafted the manuscript. C.M. and J.Q. designed and provided advice on the manuscript. H.Z. supervised the study. Z.Z. initiated and managed the project. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Haiying Zhang or Zhiyong Zhang.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Guilin Medical University (No.20180702–3).

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Informed consent was obtained from all participants included in the study.

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The authors have no relevant financial or non-financial interests to disclose.

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Xu, X., Mo, C., Qin, J. et al. Association between Copper Exposure and Cognitive Function: A Cross-Sectional Study in a County, Guangxi, China. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04296-0

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