Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
권호 표지
DOI QR코드

DOI QR Code

Association between Cognitive Decline and Ten Heavy Metals

인지기능 저하와 체내 중금속 10종 간 연관성 분석

  • Chaelyn, Lim (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Seungho, Lee (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Sang Min, Seo (Department of Psychiatry, College of Medicine, Dong-A University) ;
  • Kyung Won, Park (Department of Neurology, College of Medicine, Dong-A University) ;
  • Gwon-Min, Kim (Medical Research Institute, Pusan National University) ;
  • Byeong Moo, Choe (Department of Psychiatry, College of Medicine, Dong-A University) ;
  • Byoung-Gwon, Kim (Department of Preventive Medicine, College of Medicine, Dong-A University) ;
  • Hyun Ju, Lim (Environmental Health Center for Busan, Dong-A University) ;
  • Young-Seoub, Hong (Department of Preventive Medicine, College of Medicine, Dong-A University)
  • 임채린 (동아대학교 의과대학 예방의학교실) ;
  • 이승호 (동아대학교 의과대학 예방의학교실) ;
  • 서상민 (동아대학교 의과대학 정신건강의학교실) ;
  • 박경원 (동아대학교 의과대학 신경과학교실) ;
  • 김권민 (부산대학교 의학연구소) ;
  • 최병무 (동아대학교 의과대학 정신건강의학교실) ;
  • 김병권 (동아대학교 의과대학 예방의학교실) ;
  • 임현주 (부산광역시 환경보건센터) ;
  • 홍영습 (동아대학교 의과대학 예방의학교실)
  • Received : 2022.12.01
  • Accepted : 2022.12.20
  • Published : 2022.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Due to the rapid aging of the South Korean population, neurological diseases such as dementia are increasing. Many studies have reported that the incidence of dementia is associated with environmental factors along with age. Objectives: This study analyzed the association between cognitive function and ten heavy metals in the body: arsenic, aluminum, chromium, manganese, cobalt, nickel, iron, copper, zinc, and lead. Methods: From 2018 to 2019, a total of 120 participants who suffered from cognitive impairment were recruited for this study. Blood and urine samples were collected and analyzed for heavy metal concentrations using an inductively coupled plasma mass spectrometer. Demographic information was obtained through face-to-face questionnaires completed by a trained investigator. Cognitive function was evaluated with the Korean version of the Mini-Mental State Examination and the Korean version of the Boston Name Waiting Test. The associations between cognitive function scores and heavy metal concentrations were analyzed using multiple logistic regression analysis. Results: The average age of the 120 participants was 72.7 years, and 69.2% were female. The mean of the MMSE-K and K-BNT scores were 22.9 and 37.9, respectively. The geometric mean of aluminum (Al) was 8.42 ㎍/L. MMSE-K was associated with iron (Fe), but the significance was removed in the logistic regression based on 24 points. K-BNT was significantly associated with aluminum and the odds ratio for K-BNT above 38 decreased by 45% as the aluminum concentration increased. Conclusions: The association between aluminum and the K-BNT score indicated that aluminum is associated with language-related cognitive decline. Based on this result, further study will be conducted by considering co-exposure effects of heavy metals including aluminum.

Keywords

Acknowledgement

본 연구는 환경부·한국환경보건학회 환경보건센터 "2022년 환경보건 전문인력 양성사업(IV)"에서 연구비를 지원받아 동아대학교병원 신경과와 부산시 환경보건센터의 협업으로 수행되었습니다. 진료와 사업수행에 관한 모든 지원에 감사드립니다.

References

  1. United Nations. World Population Prospects: The 2022 Revision. Available: https://www.un.org/development/desa/pd/sites/www.un.org.development.desa.pd/files/wpp2022_summary_of_results.pdf [accessed 25 November 2022].
  2. Statistics Korea. Population Projections for Korea: 2020~2070. Available: http://kostat.go.kr/assist/synap/preview/skin/miri.html?fn=d5ee78458568914110605&rs=/assist/synap/preview [accessed 25 November 2022].
  3. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: review. JAMA. 2019; 322(16): 1589-1599. https://doi.org/10.1001/jama.2019.4782
  4. Bassil N, Mollaei C. Alzheimer's dementia: a brief review. J Med Liban. 2012; 60(4): 192-199.
  5. Sachdev PS, Blacker D, Blazer DG, Ganguli M, Jeste DV, Paulsen JS, et al. Classifying neurocognitive disorders: the DSM-5 approach. Nat Rev Neurol. 2014; 10(11): 634-642. https://doi.org/10.1038/nrneurol.2014.181
  6. Alzheimer's Association. 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020; 16(3): 391-460. https://doi.org/10.1002/alz.12278
  7. Lee HJ, Park MK, Seo YR. Pathogenic mechanisms of heavy metal induced-Alzheimer's disease. Toxicol Environ Health Sci. 2018; 10(1): 1-10. https://doi.org/10.1007/s13530-018-0340-x
  8. Miodovnik A. Environmental neurotoxicants and developing brain. Mt Sinai J Med. 2011; 78(1): 58-77. https://doi.org/10.1002/msj.20237
  9. World Health Organization. Health Risks of Heavy Metals from Long-range Transboundary Air Pollution. Available: https://apps.who.int/iris/bitstream/handle/10665/107872/9789289071796-eng.pdf?sequence=1&isAllowed=y [accessed 16 December 2022].
  10. World Health Organization. Action is Needed on Chemicals of Major Public Health Concern. Geneva: World Health Organization; 2010.
  11. Bakulski KM, Seo YA, Hickman RC, Brandt D, Vadari HS, Hu H, et al. Heavy metals exposure and Alzheimer's disease and related dementias. J Alzheimers Dis. 2020; 76(4): 1215-1242. https://doi.org/10.3233/JAD-200282
  12. Killin LO, Starr JM, Shiue IJ, Russ TC. Environmental risk factors for dementia: a systematic review. BMC Geriatr. 2016; 16(1): 175. https://doi.org/10.1186/s12877-016-0342-y
  13. Hao W, Hao C, Wu C, Xu Y, Wu S, Lu X, et al. Aluminum impairs cognitive function by activating DDX3X-NLRP3-mediated pyroptosis signaling pathway. Food Chem Toxicol. 2021; 157: 112591. https://doi.org/10.1016/j.fct.2021.112591
  14. Ahmad Rather M, Justin-Thenmozhi A, Manivasagam T, Saravanababu C, Guillemin GJ, Essa MM. Asiatic acid attenuated aluminum chloride-induced tau pathology, oxidative stress and apoptosis via AKT/GSK-3β signaling pathway in Wistar rats. Neurotox Res. 2019; 35(4): 955-968. https://doi.org/10.1007/s12640-019-9999-2
  15. Shin MH, Lee SK, Kim KH, Choi JW. Correlation between dementia and lead, cadmium, mercury, and manganese concentrations in the blood. J Environ Health Sci. 2020; 46(3): 267-275. https://doi.org/10.5668/JEHS.2020.46.3.267
  16. Lee JY, Kim JH, Choi DW, Lee DW, Park JH, Yoon HJ, et al. The association of heavy metal of blood and serum in the Alzheimer's diseases. Toxicol Res. 2012; 28(2): 93-98. https://doi.org/10.5487/TR.2012.28.2.093
  17. Kwak JY, Kook SH. The naming ability of traumatic brain injured patients with language disturbance. Korean J Clin Psychol. 2002; 21(1): 75-91.
  18. Park JH, Kwon YC. Modification of the mini-mental state examination for use in the elderly in a non-western society. Part 1. Development of Korean version of mini-mental state examination. Int J Geriatr Psychiatry. 1990; 5(6): 381-387. https://doi.org/10.1002/gps.930050606
  19. Kim JM, Shin IS, Yoon JS, Lee HY. Comparison of diagnostic validities between MMSE-K and K-MMSE for screening of dementia. J Korean Neuropsychiatr Assoc. 2003; 42(1): 124-130.
  20. Kim H, Kim EY, Na DL. Naming deficits in patients with dementia of the Alzheimer type: error analysis of Korean version-Boston naming test. J Korean Neurol Assoc. 1997; 15(5): 1012-1021.
  21. Cha Y, Lee JY, Kim JS, Lee JB, Koo BH. Clinical usefulness of combined Korean Boston naming test and delayed recall test in diagnosing dementia of the Alzheimer's type. J Korean Soc Biol Ther Psychiatry. 2011; 17(1): 30-37.
  22. Yoon CS. Limit of detection and quantification of low-concentration substance meansurement analysis and Processing of below data. In: KOSHA, editors. 2005 Work environment measurement institution quality control education collection. Ulsan: KOSHA; 2005.
  23. Kwon YC, Park JH. Korean version of mini-mental state examination (MMSE-K). J Korean Neuropsychiatr Assoc. 1989; 28(1): 123-135.
  24. Cummings JL. Subcortical Dementia. New York: Oxford University Press; 1990. p.251-259.
  25. Parlato V, Carlomagno S, Merla F, Bonavita V. Patterns of verbal memory impairment in dementia. Alzheimer disease versus multinfarctual dementia. Acta Neurol (Napoli). 1988; 10(6): 343-351.
  26. Afridi HI, Kazi TG, Kazi AG, Shah F, Wadhwa SK, Kolachi NF, et al. Levels of arsenic, cadmium, lead, manganese and zinc in biological samples of paralysed steel mill workers with related to controls. Biol Trace Elem Res. 2011; 144(1-3): 164-182. https://doi.org/10.1007/s12011-011-9063-4
  27. ATSDR. Toxicological Profile for Aluminum. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp22.pdf [accessed 28 November 2022].
  28. ATSDR. Toxicological Profile for Chromium. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp7.pdf [accessed 28 November 2022].
  29. ATSDR. Toxicological Profile for Arsenic. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp2.pdf [accessed 28 November 2022].
  30. ATSDR. Toxicological Profile for Manganese. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp151.pdf [accessed 28 November 2022].
  31. ATSDR. Toxicological Profile for Nickel. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp15.pdf [accessed 28 November 2022].
  32. ATSDR. Toxicological Profile for Lead. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp13.pdf [accessed 15 December 2022].
  33. CDC. National Health and Nutrition Examination Survey: NHANES 2015-2016 Laboratory Data. Available: https://wwwn.cdc.gov/nchs/nhanes/search/datapage.aspx?Component=Laboratory&CycleBeginYear=2015 [accessed 28 November 2022].
  34. ATSDR. Toxicological Profile for Zinc. Available: https://www.atsdr.cdc.gov/ToxProfiles/tp60.pdf [accessed 28 November 2022].
  35. Iqbal G, Zada W, Mannan A, Ahmed T. Elevated heavy metals levels in cognitively impaired patients from Pakistan. Environ Toxicol Pharmacol. 2018; 60: 100-109.
  36. Tomljenovic L. Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link? J Alzheimers Dis. 2011; 23(4): 567-598. https://doi.org/10.3233/JAD-2010-101494
  37. Rondeau V, Jacqmin-Gadda H, Commenges D, Helmer C, Dartigues JF. Aluminum and silica in drinking water and the risk of Alzheimer's disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort. Am J Epidemiol. 2009; 169(4): 489-496. https://doi.org/10.1093/aje/kwn348
  38. Shin RW, Lee VM, Trojanowski JQ. Aluminum modifies the properties of Alzheimer's disease PHF tau proteins in vivo and in vitro. J Neurosci. 1994; 14(11 Pt 2): 7221-7233. https://doi.org/10.1523/JNEUROSCI.14-11-07221.1994
  39. Exley C, Price NC, Kelly SM, Birchall JD. An interaction of beta-amyloid with aluminium in vitro. FEBS Lett. 1993; 324(3): 293-295. https://doi.org/10.1016/0014-5793(93)80137-J
  40. Sakamoto T, Saito H, Ishii K, Takahashi H, Tanabe S, Ogasawara Y. Aluminum inhibits proteolytic degradation of amyloid beta peptide by cathepsin D: a potential link between aluminum accumulation and neuritic plaque deposition. FEBS Lett. 2006; 580(28-29): 6543-6549. https://doi.org/10.1016/j.febslet.2006.10.075
  41. Mold M, Linhart C, Gomez-Ramirez J, Villegas-Lanau A, Exley C. Aluminum and amyloid-β in familial Alzheimer's disease. J Alzheimers Dis. 2020; 73(4): 1627-1635. https://doi.org/10.3233/JAD-191140
  42. Alzheimer A. [Uber einen eigenartigen schweren Er Krankungsprozeβ der Hirnrinde]. Neurol Cent. 1906; 25: 1129-1136. German.
  43. Camerer C. Deficits in word retrieval in Alzheimer's Disease [dissertation]. [Dusseldorf]: Heinrich-Heine-Universitat Dusseldorf; 2017.
  44. Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011; 283(2-3): 65-87. https://doi.org/10.1016/j.tox.2011.03.001
  45. Oteiza PI, Mackenzie GG, Verstraeten SV. Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. Mol Aspects Med. 2004; 25(1-2): 103-115. https://doi.org/10.1016/j.mam.2004.02.012
  46. Selvi Oztorun H, Cinar E, Turgut T, Mut Surmeli D, Bahsi R, Atmis V, et al. The impact of treatment for iron deficiency and iron deficiency anemia on nutritional status, physical performance, and cognitive function in geriatric patients. Eur Geriatr Med. 2018; 9(4): 493-500. https://doi.org/10.1007/s41999-018-0065-z
  47. Jin R, Zhu X, Shrubsole MJ, Yu C, Xia Z, Dai Q. Associations of renal function with urinary excretion of metals: evidence from NHANES 2003-2012. Environ Int. 2018; 121(Pt 2): 1355-1362. https://doi.org/10.1016/j.envint.2018.11.002
  48. Bulka CM, Mabila SL, Lash JP, Turyk ME, Argos M. Arsenic and obesity: a comparison of urine dilution adjustment methods. Environ Health Perspect. 2017; 125(8): 087020. https://doi.org/10.1289/ehp1202
  49. Kim S, Vermeulen R, Waidyanatha S, Johnson BA, Lan Q, Rothman N, et al. Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism. Carcinogenesis. 2006; 27(4): 772-781. https://doi.org/10.1093/carcin/bgi297
  50. Cheng BJ, Wang J, Meng XL, Sun L, Hu B, Li HB, et al. The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults. Ecotoxicol Environ Saf. 2022; 231: 113182. https://doi.org/10.1016/j.ecoenv.2022.113182