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The Role of Iron and Other Trace Elements on Mental Development and Cognitive Function

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Psychiatry and Neuroscience Update

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Abstract

In this chapter we review the effect of some trace elements. Consequences of exposure or modification of the levels of iron, lead, methylmercury, mercury, cadmium, manganese, arsenic, and copper on the central nervous system (CNS) and learning and cognition will be discussed. We review the effects of iron deficiency (ID) and anemia on cognitive function and the relationship between its statuses on developmental outcome and the state of the adult brain. The iron needs of the brain vary depending on the stage of the life cycle and the cell types. ID has been reported to have a role in brain development and some trace elements are routinely involved in metabolic processes and oxidation-reactions in the CNS which could have a possible effect on cognitive functions. Behavioral and cognitive adverse effects caused by exposure to lead by the fetus and infant are discussed, as well as fetal and infant exposure to high concentrations of methylmercury and cadmium on CNS development and their cognitive consequences. A significant correlation between elevated levels of cadmium and lead and decreased verbal development and lower IQ has been shown in children. The potential effects associated with the accumulation of manganese in the CNS decreasing levels of neurotransmitter. Arsenic exposure can produce neurocognitive deficits in children. Dysregulation of iron homeostasis is also a critical feature in Alzheimer disease (AD), Parkinson disease (PD), Friedreich ataxia (FA), and neurodegeneration with brain iron accumulation. Copper toxicity and zinc deficiency are associated with cognition loss and AD. Consequently, we consider an update on these issues necessary.

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References

  1. Kesse-Guyot E, Fezeu L, Jeandel C, Ferry M, Andreeva V, Amieva H, et al. French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the supplementation in vitamins and mineral antioxidants (SU.VI.MAX) trial. Am J Clin Nutr. 2011;94:892–9.

    Article  CAS  PubMed  Google Scholar 

  2. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Richter L, Strupp B. Child development in developing countries 1—developmental potential in the first 5 years for children in developing countries. Lancet. 2007;369:60–70.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Benton D. Micro-nutrient supplementation and the intelligence of children. Neurosci Biobehav Rev. 2001;25:297–309.

    Article  CAS  PubMed  Google Scholar 

  4. Eilander A, Gera T, Sachdev HS, Transler C, van der Knaap HCM, Kok FJ, et al. Multiple micronutrient supplementation for improving cognitive performance in children: systematic review of randomized controlled trials. Am J Clin Nutr. 2010;91:115–30.

    Article  CAS  PubMed  Google Scholar 

  5. De Benoist B, Andersson M, Takkouche B, Egli I. Prevalence of iodine deficiency worldwide. Lancet. 2003;362:1859–60.

    Article  PubMed  Google Scholar 

  6. Smorgon C, Mari E, Atti AR, Dalla Nora E, Zamboni PF, Calzoni F, et al. Trace elements and cognitive impairment: an elderly cohort study. Arch Gerontol Geriatr Suppl. 2004;9:393–402.

    Article  CAS  PubMed  Google Scholar 

  7. Sandstrom B. Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr. 2001;85 suppl 2:S181–5.

    Article  CAS  PubMed  Google Scholar 

  8. Thomas DG, Grant SL, Aubuchon-Endsley NL. The role of iron in neurocognitive development. Dev Neuropsychol. 2009;34(2):196–222.

    Article  PubMed  Google Scholar 

  9. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(2S-2):649S–66S.

    CAS  PubMed  Google Scholar 

  10. Lozoff B. Iron deficiency and child development. Food Nutr Bull. 2007;28(4 Suppl):S560–71.

    Article  PubMed  Google Scholar 

  11. Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131(2S-2):568S–79S.

    CAS  PubMed  Google Scholar 

  12. Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med. 2012;366:348–59.

    Article  CAS  PubMed  Google Scholar 

  13. Pinero DJ, Hu J, Connor JR. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer’s diseased brains. Cell Mol Biol (Noisy-le-grand). 2000;46(4):761–76.

    CAS  Google Scholar 

  14. Altamura S, Muckenthaler MU. Iron toxicity in diseases of aging: Alzheimer’s disease, Parkinson’s disease and atherosclerosis. J Alzheimers Dis. 2009;16(4):879–95.

    PubMed  Google Scholar 

  15. Hallgren B, Sourander P. The effect of age on the non-haem iron in the human brain. J Neurochem. 1958;3:41–51.

    Article  CAS  PubMed  Google Scholar 

  16. Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979;3:79–83.

    Article  CAS  PubMed  Google Scholar 

  17. Coe CL, Lutbach GR. Novel mechanism accounting for prenatal effects on the development of infant immunity. PNIRS Abstracts. 1991;2–12.

    Google Scholar 

  18. Dallman PR, Siimes M, Manies EC. Brain iron: persistent deficiency following short-term iron deprivation in the young rat. Br J Haematol. 1975;31:209–15.

    Article  CAS  PubMed  Google Scholar 

  19. Dallman PR, Spirito RA. Brain iron in the rat: extremely slow turnover in normal rat may explain the long-lasting effects of early iron deficiency. J Nutr. 1977;107:1075–81.

    CAS  PubMed  Google Scholar 

  20. Beard JL, Wiesinger JA, Connor JR. Pre- and postweaning iron deficiency alters myelination in Sprague-Dawley rats. Dev Neurosci. 2003;25:308–15.

    Article  CAS  PubMed  Google Scholar 

  21. Serpa RFB, de Jesus EFO, Anjos MJ, Lopes RT, do Carmo MGT, Rocha MS, et al. Cognitive impairment related changes in the elemental concentration in the brain of old rats. Spectrochimica Acta B. 2006;61:1219–23.

    Article  CAS  Google Scholar 

  22. Pollit E. Iron deficiency and cognitive function. Annu Rev Nutr. 1993;13:521–37.

    Article  Google Scholar 

  23. Felt BT, Lozoff B. Brain iron and behaviour of rats are not normalized by treatment of iron deficiency anemia during early development. J Nutr. 1996;126:693–701.

    CAS  PubMed  Google Scholar 

  24. Lozoff B, Jimenez E, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med. 1991;325:687–94.

    Article  CAS  PubMed  Google Scholar 

  25. Fretham SJB, Carlson ES, Georgieff MK. The role of iron in learning and memory. Adv Nutr. 2011;2:112–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Rice D, Barone Jr S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108 Suppl 3:511–33.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Nelson CA. The ontogeny of human memory: a cognitive neuroscience perspective. Dev Psychol. 1995;31:723–38.

    Article  Google Scholar 

  28. Pokorny J, Yamamoto T. Postnatal ontogenesis of hippocampal CA1 area in rats. II. Development of ultrastructure in stratum lacunosum and molecular. Brain Res Bull. 1981;7:121–30.

    Article  CAS  PubMed  Google Scholar 

  29. Bekenstein JW, Lothman EW. An in vivo study of the ontogeny of long-term potentiation (LTP) in the CA1 region and in the dentate gyrus of the rat hippocampal formation. Brain Res Dev Brain Res. 1991;63:245–51.

    Article  CAS  PubMed  Google Scholar 

  30. De Deungria M, Rao R, Wobken JD, Luciana M, Nelson CA, Georgieff MK. Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain. Pediatr Res. 2000;48:169–76.

    Article  CAS  PubMed  Google Scholar 

  31. Dallman PR. Biochemical basis for the manifestations of iron deficiency. Annu Rev Nutr. 1986;6:13–40.

    Article  CAS  PubMed  Google Scholar 

  32. Chang DT, Reynolds IJ. Differences in mitochondrial movement and morphology in young and mature primary cortical neurons in culture. Neuroscience. 2006;141:727–36.

    Article  CAS  PubMed  Google Scholar 

  33. Wells JC. The thrifty phenotype as an adaptive maternal effect. Biol Rev Camb Philos Soc. 2007;82:143–72.

    Article  PubMed  Google Scholar 

  34. Le NT, Richardson DR. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta. 2002;1603:31–46.

    CAS  PubMed  Google Scholar 

  35. Sheftel A, Stehling O, Lill R. Iron-sulfur proteins in health and disease. Trends Endocrinol Metab. 2010;21:302–14.

    Article  CAS  PubMed  Google Scholar 

  36. Mattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008;60:748–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Lill R, Fekete Z, Sipos K, Rotte C. Is there an answer? Why are mitochondria essential for life? IUBMB Life. 2005;57:701–3.

    Article  CAS  PubMed  Google Scholar 

  38. Burgoyne RD. Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling. Nat Rev Neurosci. 2007;8:182–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Ulten L. Iron deficiency and cognition. Scand J Nutr. 2003;47(3):152–6.

    Article  Google Scholar 

  40. Idjradinata P, Pollitt E. Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet. 1993;341:1–4.

    Article  CAS  PubMed  Google Scholar 

  41. World Health Organization. Worldwide prevalence of anemia 1993-2005: WHO global database on anaemia. Geneva: WHO; 2008.

    Google Scholar 

  42. Martins S, Logan S, Gilbert RE. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia. Cochrane Database Syst Rev. 2001;2, CD001444.

    PubMed  Google Scholar 

  43. Sachdev H, Gera T, Nestel P. Effect of iron supplementation on mental and motor development in children: systematic review of randomized controlled trials. Public Health Nutr. 2005;8:117–32.

    Article  PubMed  Google Scholar 

  44. Sachdev HPS, Gera T, Nestel P. Effect of iron supplementation on physical growth in children: systematic review of randomised controlled trials. Public Health Nutr. 2006;9:904–20.

    Article  PubMed  Google Scholar 

  45. Iannotti LL, Tielsch JM, Black MM, Black RE. Iron supplementation in early childhood: health benefits and risks. Am J Clin Nutr. 2006;84:1261–76.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Gaskell H, Derry S, Moore RA, McQuay HJ, Alatorre J. Prevalence of anaemia in older persons: systematic review. BMC Geriatr. 2008;8:2318–21.

    Google Scholar 

  47. Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Dye L, Hooper L. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutr J. 2010;9:4–16.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. McClung JP, Murray-Kolb LE. Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance. Annu Rev Nutr. 2013;33:271–88.

    Article  CAS  PubMed  Google Scholar 

  49. Breyman C, Romer T, Dudenhausen JW. Treatment of iron deficiency in women. Geburtsh Frauenheilk. 2013;73:256–61.

    Article  CAS  Google Scholar 

  50. Lind T, Lönnerdal B, Stenlund H, Gamayanti IL, Ismail D, Seswandhana R, et al. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development. Am J Clin Nutr. 2004;80:729–36.

    CAS  PubMed  Google Scholar 

  51. Stoecker BJ, Abebe Y, Hubbs-Tait L, Kennedy TS, Gibson RS, Arbide I, et al. Zinc status and cognitive function of pregnant women in Southern Ethiopia. Eur J Clin Nutr. 2009;63:916–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Siddappa AJ, Rao RB, Wobken JD, Casperson K, Leibold EA, Connor JR, et al. Iron deficiency alters iron regulatory protein and iron transport protein expression in the perinatal rat brain. Pediatr Res. 2003;53:800–7.

    Article  CAS  PubMed  Google Scholar 

  53. Sadrzadeh SMH, Saffari Y. Iron and brain disorders. Am J Clin Pathol. 2004;121 Suppl 1:S64–70.

    PubMed  Google Scholar 

  54. Koppenol WH, Butler J, Van Leeuwen JW. The Haber-Weiss cycle. Photochem Photobiol. 1978;28:655–60.

    Article  CAS  Google Scholar 

  55. Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem. 1992;59:1609–23.

    Article  CAS  PubMed  Google Scholar 

  56. Halliwell B, Gutteridge JM. The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med. 1985;8:89–193.

    Article  CAS  PubMed  Google Scholar 

  57. Demougeot C, Marie C, Beley A. Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Sci. 2000;67:399–410.

    Article  CAS  PubMed  Google Scholar 

  58. Sadrzadeh SMH, Graf E, Panter SS, Hallaway PE, Eaton JW. Hemoglobin. A biologic Fenton reagent. J Biol Chem. 1984;259:14354–6.

    CAS  PubMed  Google Scholar 

  59. Benarroch EE. Brain iron homeostasis and neurodegenerative disease. Neurology. 2009;72(16):1436–40.

    Article  PubMed  Google Scholar 

  60. Rouault TA, Cooperman S. Brain iron metabolism. Semin Pediatr Neurol. 2006;13:142–8.

    Article  PubMed  Google Scholar 

  61. Moos T, Rosengren Nielsen T, Skjorringe T, Morgan EH. Iron trafficking inside the brain. J Neurochem. 2007;103:1730–40.

    Article  CAS  PubMed  Google Scholar 

  62. Madsen E, Gitlin JD. Copper and iron disorders of the brain. Annu Rev Neurosci. 2007;30:317–37.

    Article  CAS  PubMed  Google Scholar 

  63. Morgan EH, Moos T. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol. 2000;20:77–95.

    Article  PubMed  Google Scholar 

  64. Vidal R, Miravalle L, Gao X, et al. Expression of a mutant form of the ferritin light chain gene induces neurodegeneration and iron overload in transgenic mice. J Neurosci. 2008;28:60–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Zecca L, Casella L, Albertini A, Barbeito AG, Baraibar MA, Hekmatyar SK, et al. Neuromelanin can protect against iron-mediated oxidative damage in system modeling iron overload of brain aging and Parkinson’s disease. J Neurochem. 2008;106:1866–75.

    CAS  PubMed  Google Scholar 

  66. Rouault TA, Tong WH. Iron-sulfur cluster biogenesis and human disease. Trends Genet. 2008;24:398–407.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Li K, Besse EK, Ha D, Kovtunovych G, Rouault TA. Iron dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia. Hum Mol Genet. 2008;17:2265–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Zanella I, Derosas M, Corrado M, Cocco E, Cavadini P, Biasiotto G, et al. The effects of frataxin silencing in HeLa cells are rescued by the expression of human mitochondrial ferritin. Biochim Biophys Acta. 2008;1782:90–8.

    Article  CAS  PubMed  Google Scholar 

  69. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004;5:863–73.

    Article  CAS  PubMed  Google Scholar 

  70. Cheah JH, Kim SF, Hester LD, Clancy KW, Patterson 3rd SE, Papadopoulos V, et al. NMDA receptor nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Neuron. 2006;51:431–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci. 1998;158:47–52.

    Article  CAS  PubMed  Google Scholar 

  72. Zerbinatti CV, Wozniak DF, Cirrito J, Cam JA, Osaka H, Bales KR, et al. Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor–related protein. Proc Natl Acad Sci U S A. 2004;101:1075–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Berg D, Youdim MB. Role of iron in neurodegenerative disorders. Top Magn Reson Imaging. 2006;17:5–17.

    Article  PubMed  Google Scholar 

  74. Maynard CJ, Cappai R, Volitakis I, Cherny RA, White AR, Beyreuther K, et al. Overexpression of Alzheimer’s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J Biol Chem. 2002;277:44670–6.

    Article  CAS  PubMed  Google Scholar 

  75. Kim DK, Seo MY, Lim SW, Kim S, Kim JW, Carroll BJ, et al. Serum melanotransferrin, p97 as a biochemical marker of Alzheimer’s disease. Neuropsychopharmacology. 2001;25:84–90.

    Article  CAS  PubMed  Google Scholar 

  76. Lehmann DJ, Worwood M, Ellis R, Wimhurst VL, Merrywheather-Clarke AT, Warden DR, et al. Iron genes, iron load and risk of Alzheimer’s disease. J Med Genet. 2006;43:e52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Wilson RB. Iron dysregulation in Friedreich ataxia. Semin Pediatr Neurol. 2006;13:166–75.

    Article  PubMed  Google Scholar 

  78. Puccio H, Simon D, Cossée M, Criqui-Filipe P, Tiziano F, Melki J, et al. Mouse models of Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet. 2001;27:181–6.

    Article  CAS  PubMed  Google Scholar 

  79. Alper G, Narayanan V. Friedreich’s ataxia. Pediatr Neurol. 2003;28:335–41.

    Article  PubMed  Google Scholar 

  80. Lodi R, Hart PE, Rajagopolan B, Taylor DJ, Crilley JG, Bradley JL, et al. Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich’s ataxia. Ann Neurol. 2001;49:590–6.

    Article  CAS  PubMed  Google Scholar 

  81. Youdim MB, Ben-Shachar D, Riederer P. Iron in brain function and dysfunction with emphasis on Parkinson’s disease. Eur Neurol. 1991;319 suppl 1:34–40.

    Article  Google Scholar 

  82. Faucheux B, Hirsch E. Iron homeostasis and Parkinson’s disease. Ann Biol Clin (Paris). 1998;56(Spec No):23–30.

    CAS  PubMed  Google Scholar 

  83. Spatz H. Über den Eisennachweis in Gehirn, besonders in Zentren des extrapyramidal-motorischen Systems (On the visualization of iron in the brain, especially in the centers of the extrapyramidal motor system). Z Ges Neurol Psychiatr. 1922;77:261–390.

    Article  CAS  Google Scholar 

  84. Double KL, Gerlach M, Schunemann V, Trautwein AX, Zecca L, Gallorini M, et al. Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochem Pharmacol. 2003;66:489–94.

    Article  CAS  PubMed  Google Scholar 

  85. Berg D, Gerlach M, Youdim MB, Double KL, Zecca L, Riederer P, et al. Brain iron pathways and their relevance to Parkinson’s disease. J Neurochem. 2001;79:225–36.

    Article  CAS  PubMed  Google Scholar 

  86. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden–Spatz syndrome. Nat Genet. 2001;28:345–9.

    Article  CAS  PubMed  Google Scholar 

  87. Hayflick SJ. Neurodegeneration with brain iron accumulation: from genes to pathogenesis. Semin Pediatr Neurol. 2006;13:182–5.

    Article  PubMed  Google Scholar 

  88. Bertrand E. Neurodegeneration with brain iron accumulation, type-I (NBIA-I) (formerly Hallervorden-Spatz, disease), Par I: clinical manifestation and treatment [in Polish]. Neurol Neurochir Pol. 2002;36:947–58.

    PubMed  Google Scholar 

  89. Burn J, Chinnery PF. Neuroferritinopathy Semin Pediatr Neurol. 2006;13:176–81.

    Article  PubMed  Google Scholar 

  90. Mancuso M, Davidzon G, Kurlan RM, Tawil R, Bonilla E, Di Mauro S, et al. Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights. J Neuropathol Exp Neurol. 2005;64:280–94.

    CAS  PubMed  Google Scholar 

  91. Chinnery PF, Crompton DE, Birchall D, Jackson MJ, Coulthard A, Lombès A, et al. Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. Brain. 2007;130:110–9.

    Article  PubMed  Google Scholar 

  92. Fasano A, Colosimo C, Miyajima H, Tonali PA, Re TJ, Bentivoglio AR. Aceruloplasminemia: a novel mutation in a family with marked phenotypic variability. Mov Disord. 2008;23:751–5.

    Article  PubMed  Google Scholar 

  93. McNeill A, Pandolfo M, Kuhn J, Shang H, Miyajima H. The neurological presentation of ceruloplasmin gene mutations. Eur Neurol. 2008;60:200–5.

    Article  PubMed  Google Scholar 

  94. Kono S, Miyajima H. Molecular and pathological basis of aceruloplasminemia. Biol Res. 2006;39:15–23.

    Article  CAS  PubMed  Google Scholar 

  95. Institute for Environment and Health/Institute of Occupational Medicine. Occupational exposure limits: criteria document for manganese and inorganic manganese compounds. Web report W17. Leicester: Medical Research Council, Institute for Environment and Health; 2004. http://www.le.ac.uk/ieh. Accessed 25 March 2008.

    Google Scholar 

  96. World Health Organization. Manganese. Environmental health criteria 17. Geneva: WHO; 1981.

    Google Scholar 

  97. Ellingsen DG, Konstantinov R, Bast-Pettersen R, Merkurjeva L, Chashchin M, Thomassen Y, et al. A neurobe- havioral study of current and former welders exposed to manganese. NeuroToxicology. 2008;29:48–59.

    Article  CAS  PubMed  Google Scholar 

  98. Bast-Pettersen R, Ellingsen DG, Hetland SM, Thomassen Y. Neuropsy- chological function in manganese alloy plant workers. Int Arch Occup Environ Health. 2004;77:277–87.

    Article  CAS  PubMed  Google Scholar 

  99. Klos KJ, Chandler M, Kumar N, Ahlskog JE, Josephs KA. Neuropsychological profiles of manganese neurotoxicity. Eur J Neurol. 2006;13:1139–41.

    Article  CAS  PubMed  Google Scholar 

  100. Zoni S, Albini E, Lucchini R. Neuropsychological testing for the assessment of neurotoxicity: a review and a proposal. Am J Ind Med. 2007;50:812–30.

    Article  CAS  PubMed  Google Scholar 

  101. Winder BS, Salmon AG, Marty MA. Inhalation of an essential metal: development of reference exposure levels for manganese. Regul Toxicol Pharmacol. 2010;57:195–9.

    Article  CAS  PubMed  Google Scholar 

  102. Santos-Burgoa C, Rios C, Mercado LA, Arechiga-Serrano R, Cano-Valle F, Eden-Wynter RA, et al. Exposure to manganese: health effects on the general population, a pilot study in central Mexico. Environ Res. 2001;85(A):90–104.

    Article  CAS  PubMed  Google Scholar 

  103. Winder BS. Manganese in the air: are children at greater risk than adults? J Toxicol Environ Health. 2010;73(A):156–8.

    Article  CAS  Google Scholar 

  104. US Environmental Protection Agency. Drinking water health advisory for manganese. Washington, DC: US Environmental Protection Agency; 2004. Report 822R04003.

    Google Scholar 

  105. Keen CL, Bell JG, Lonnerdal B. The effect of age on manganese uptake and retention from milk and infant formulas in rats. J Nutr. 1986;116:395–402.

    CAS  PubMed  Google Scholar 

  106. Aschner M. Manganese: brain transport and emerging research needs. Environ Health Perspect. 2000;108(3):429–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  107. Iinuma Y, Kubota M, Uchiyama M, Yagi M, Kanada S, Yamazaki S, et al. Whole-blood manganese levels and brain manganese accumulation in children receiving long-term home parenteral nutrition. Pediatr Surg Int. 2003;19:268–72.

    Article  PubMed  Google Scholar 

  108. Menezes-Filho JA, Bouchard M, Sarcinelli PN, Moreira JC. Manganese exposure and the neuropsychological effect on children and adolescents: a review. Rev Panam Salud Publica. 2009;26:541–8.

    Article  PubMed  Google Scholar 

  109. Dorner K, Dziadzka S, Hohn A, Sievers E, Oldigs HD, Schulz-Lell G, et al. Longitudinal manganese and copper balances in young infants and preterm infants fed on breast-milk and adapted cow’s milk formulas. Br J Nutr. 1989;61:559–72.

    Article  CAS  PubMed  Google Scholar 

  110. Mena I, Horiuchi K, Burke K, Cotzias GC. Chronic manganese poisoning: individual susceptibility and absorption of iron. Neurology. 1969;19:1000–6.

    Article  CAS  PubMed  Google Scholar 

  111. Cotzias GC, Miller ST, Papavasiliou PS, Tang LC. Interactions between manganese and brain dopamine. Med Clin North Am. 1976;60:729–38.

    CAS  PubMed  Google Scholar 

  112. Iregren A. Manganese neurotoxicity in industrial exposures: proof of effects, critical exposure level, and sensitive tests. Neurotoxicology. 1999;20:315–24.

    CAS  PubMed  Google Scholar 

  113. Tanaka S. Manganese and its compounds. In: Zenz C, editor. Occupational medicine: principles and practical applications. Chicago, IL: Year Book Medical Publishers; 1988. p. 583–9.

    Google Scholar 

  114. Mergler D. Neurotoxic effects of low level exposure to manganese in human populations. Environ Res. 1999;80:99–102.

    Article  CAS  PubMed  Google Scholar 

  115. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005;26:353–62.

    Article  CAS  PubMed  Google Scholar 

  116. Prohaska JR. Functions of trace elements in brain metabolism. Physiol Rev. 1987;67:858–901.

    CAS  PubMed  Google Scholar 

  117. Roth JA. Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination. Biol Res. 2006;39(1):45–57.

    Article  CAS  PubMed  Google Scholar 

  118. Dobson AW, Erikson KM, Aschner M. Manganese neurotoxicity. Ann N Y Acad Sci. 2004;1012:115–28.

    Article  CAS  PubMed  Google Scholar 

  119. Mergler D, Baldwin M. Early manifestations of manganese neurotoxicity in humans: an update. Environ Res. 1997;73:92–100.

    Article  CAS  PubMed  Google Scholar 

  120. Pal PK, Samii A, Calne DB. Manganese neurotoxicity: a review of clinical features, imaging and pathology. Neurotoxicology. 1999;20(2–3):227–38.

    CAS  PubMed  Google Scholar 

  121. Li D, Sham PC, Owen MJ, He L. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet. 2006;15:2276–84.

    Article  CAS  PubMed  Google Scholar 

  122. Fitsanakis VA, Au C, Erikson KM, Aschner M. The effects of manganese on glutamate, dopamine and gamma-aminobutyric acid regulation. Neurochem Int. 2006;48:426–33.

    Article  CAS  PubMed  Google Scholar 

  123. Graham DG. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease. Neurotoxicology. 1984;5:83–96.

    CAS  PubMed  Google Scholar 

  124. Antonini JM, Santamaria AB, Jenkins NT, Albini E, Lucchini A. Fate of manganese associated with the inhalation of welding fumes: potential neurological effects. Neurotoxicology. 2006;27:304–10.

    Article  CAS  PubMed  Google Scholar 

  125. Fitsanakis V, Zhang N, Avison MJ, Gore JC, Aschner JL, Aschner M. The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. Neurotoxicology. 2006;27(5):798–806.

    Article  CAS  PubMed  Google Scholar 

  126. Erikson KM, Thompson K, Aschner J, Aschner M. Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther. 2007;113(2):369–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  127. Burton NC, Guilarte TR. Manganese neurotoxicity: lessons learned from longitudinal studies in nonhuman primates. Environ Health Perspect. 2009;117(3):325–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  128. Zoni S, Lucchini RG. Manganese exposure: cognitive, motor and behavioral effects on children: a review of recent findings. Curr Opin Pediatr. 2013;25:255–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. Bouchard MF, Sauve S, Barbeau B, et al. Intellectual impairment in school-age children exposed to manganese from drinking water. Environ Health Perspect. 2011;119:138–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  130. Menezes-Filho JA, Novaes Cde O, Moreira JC, et al. Elevated manganese and cognitive performance in school-aged children and their mothers. Environ Res. 2011;111:156–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  131. Wasserman GA, Liu X, Parvez F, et al. Arsenic and manganese exposure and children’s intellectual function. Neurotoxicology. 2011;32:450–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  132. Bouchard M, Mergler D, Baldwin ME, Panisset M. Manganese cumulative exposure and symptoms: a follow-up study of alloy workers. Neurotoxicology. 2008;29:577–83.

    Article  CAS  PubMed  Google Scholar 

  133. Lucchini R, Apostoli P, Perrone C, Placidi D, Albini E, Migliorati P, et al. Long-term exposure to ‘low levels’ of manganese oxides and neuro-functional changes in ferroalloy workers. Neurotoxicology. 1999;20:287–97.

    CAS  PubMed  Google Scholar 

  134. Agency for Toxic Substances and Disease Registry ATSDR. Toxicological profile for Cadmiun. 2012. http://www.atsdr.cdc.gov/ToxProfiles/tp5.pdf

    Google Scholar 

  135. EFSA. Scientific opinion of the panel on contaminants in the food chain on a request from the European commission on cadmium in food. EFSA J. 2009;980:1–139.

    Google Scholar 

  136. Lin CM, Doyle P, Wang D, Hwang YH, Chen PC. Does prenatal cadmium exposure affect fetal and child growth? Occup Environ Med. 2011;68:641–6.

    Article  CAS  PubMed  Google Scholar 

  137. WHO/FAO. WHO: food additives series: 64, Safety evaluation of certain food additives and contaminants: 73rd meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Geneva: World Health Organization/Food and Agriculture Organization of the United Nations; 2011.

    Google Scholar 

  138. Cao Y, Chen A, Radcliffe J, Dietrich KN, Jones RL, Caldwell K, et al. Postnatal cadmium exposure, neurodevelopment, and blood pressure in children at 2, 5, and 7 years of age. Environ Health Perspect. 2009;117:1580–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  139. Kippler M, Tofail F, Hamadani JD, Gardner RM, Grantham-McGregor SM, Bottai M, et al. Early-life cadmium exposure and child development in 5-year-old girls and boys: a cohort study in rural Bangladesh. Environ Health Perspect. 2012;120:1462–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  140. Ciesielski T, Weuve J, Bellinger DC, Schwartz J, Lanphear B, Wright RO. Cadmium exposure and neurodevelopmental outcomes in U.S. children. Environ Health Perspect. 2012;120:758–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  141. Struempler RE, Larson GE, Rimland B. Hair mineral analysis and disruptive behavior in clinically normal young men. J Learn Disabil. 1985;18:609–12.

    Article  CAS  PubMed  Google Scholar 

  142. Viaene MK, Masschelein R, Leenders J, De Groof M, Swerts LJ, Roels HA. Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study. Occup Environ Med. 2000;57:19–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  143. Hart RP, Rose CS, Hamer RM. Neuropsychological effects of occupational exposure to cadmium. J Clin Exp Neuropsychol. 1989;11:933–43.

    Article  CAS  PubMed  Google Scholar 

  144. Emsley CL, Gao S, Li Y, Liang C, Ji R, Hall KS, et al. Trace element levels in drinking water and cognitive function among elderly Chinese. Am J Epidemiol. 2000;151:913–20.

    Article  CAS  PubMed  Google Scholar 

  145. Gao S, Jin Y, Unverzagt FW, Ma F, Hall KS, Murrell JR, et al. Trace element levels and cognitive function in rural elderly Chinese. J Gerontol A Biol Sci Med Sci. 2008;63:635–41.

    Article  PubMed Central  PubMed  Google Scholar 

  146. Ciesielski T, Bellinger D, Schwartz J, Hauser R, Wright R. Associations between cadmium exposure and neurocognitive test scores in a cross-sectional study of US adults. Environ Health. 2013;12:13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  147. Rai A, Maurya SK, Khare P, Srivastava A, Bandyopadhyay S. Characterization of developmental neurotoxicity of As, Cd, and Pb mixture: synergistic action of metal mixture in glial and neuronal functions. Toxicol Sci. 2010;118:586–601.

    Article  CAS  PubMed  Google Scholar 

  148. Bellinger DC. Very low lead exposures and children’s neurodevelopment. Curr Opin Pediatr. 2008;20:172–7.

    Article  PubMed  Google Scholar 

  149. Kim Y, Eun-Hee H, Hyesook P, Mina H, Yangho K, Yun-hul H, et al. Prenatal lead and cadmium co-exposure and infant neurodevelopment at 6 months of age: the mothers and children’s environmental health (MOCEH) study. Neuro Toxicology. 2013;35:15–22.

    CAS  Google Scholar 

  150. Klevay LM. Copper and cognition. Clin Neurophysiol. 2010;121(12):2177.

    Article  PubMed  Google Scholar 

  151. Salustri C, Barbati G, Ghidoni R, Quintiliani L, Ciappina S, Binetti G, et al. Is cognitive function linked to serum free copper levels? A cohort study in a normal population. Clin Neurophysiol. 2010;121(4):502–7.

    Article  CAS  PubMed  Google Scholar 

  152. Brewer GJ. Copper toxicity in Alzheimer’s disease: cognitive loss from ingestion of inorganic copper. J Trace Elem Med Biol. 2012;26(2–3):89–92.

    Article  CAS  PubMed  Google Scholar 

  153. Brewer GJ. Copper excess, zinc deficiency, and cognition loss in Alzheimer’s disease. Biofactors. 2012;38(2):107–13.

    Article  CAS  PubMed  Google Scholar 

  154. Brewer GJ. The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer’s disease. J Am Coll Nutr. 2009;28(3):238–42.

    Article  PubMed  Google Scholar 

  155. Brewer GJ. Risks of copper and iron toxicity during aging in humans. Chem Res Toxicol. 2010;23(2):319–26.

    Article  CAS  PubMed  Google Scholar 

  156. Squitti R, Ghidoni R, Scrascia F, Benussi L, Panetta V, Pasqualetti P, et al. Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals. J Alzheimers Dis. 2011;23(2):239–48.

    CAS  PubMed  Google Scholar 

  157. Mueller C, Schrag M, Crofton A, Stolte J, Muckenthaler MU, Magaki S, et al. Altered serum iron and copper homeostasis predicts cognitive decline in mild cognitive impairment. J Alzheimers Dis. 2012;29(2):341–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  158. Brewer GJ, Kaur S. Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer’s disease. Int J Alzheimers Dis. 2013;2013:586365.

    PubMed Central  PubMed  Google Scholar 

  159. Baum L, Chan IH, Cheung SK, Goggins WB, Mok V, Lam L, et al. Serum zinc is decreased in Alzheimer’s disease and serum arsenic correlates positively with cognitive ability. Biometals. 2010;23(1):173–9.

    Article  CAS  PubMed  Google Scholar 

  160. Park JH, Lee DW, Park KS, Joung H. Serum trace metal levels in Alzheimer’s disease and normal control groups. Am J Alzheimers Dis Other Demen. 2014;29(1):76–83.

    Article  PubMed  Google Scholar 

  161. Gong G, Hargrave KA, Hobson V, Spallholz J, Boylan M, Lefforge D, et al. Low-level groundwater arsenic exposure impacts cognition: a project FRONTIER study. J Environ Health. 2011;74(2):16–22.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Biochemistry, Hospital Universitario Miguel Servet-Zaragoza, Calle Padre Arrupe, S/N, Planta 3ª Servicio Bioquimica Clínica, Zaragoza, Spain

    Silvia Izquierdo-Álvarez

  2. Laboratory/Clinical Analyses Service, Galdakao–Usansolo Hospital, Galdakao, Vizcaya, Spain

    Eloísa Urrechaga-Igartua Ph.D.

  3. Department of Spectroscopy, Spanish Defense Institute of Toxicology, Madrid, Spain

    Maria Teresa Llorente-Ballesteros

  4. Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral, S/N, Zaragoza, Spain

    Jesús Fernando Escanero Ph.D.

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  1. Silvia Izquierdo-Álvarez
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  2. Eloísa Urrechaga-Igartua Ph.D.
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  3. Maria Teresa Llorente-Ballesteros
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  4. Jesús Fernando Escanero Ph.D.
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Correspondence to Silvia Izquierdo-Álvarez .

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  1. Guaymallen Mendoza, Argentina

    Pascual Ángel Gargiulo

  2. Member of the Council of the Institute of Neurobiology (Buenos Aires); Member of the Board of Certification, National Academy of Medicine (Argentina), Psychiatrist by University Complutense of Madrid and University of Buenos Aires; Former Director of National Institute of Mental Health (Argentina), Cuyo, Buenos Aires, Argentina

    Humberto Luis Mesones Arroyo

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Izquierdo-Álvarez, S., Urrechaga-Igartua, E., Llorente-Ballesteros, M.T., Escanero, J.F. (2015). The Role of Iron and Other Trace Elements on Mental Development and Cognitive Function. In: Gargiulo, P., Arroyo, H. (eds) Psychiatry and Neuroscience Update. Springer, Cham. https://doi.org/10.1007/978-3-319-17103-6_12

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