Clinical Neurophysiology
Volume 121, Issue 4 , Pages 502-507 , April 2010

Is cognitive function linked to serum free copper levels? A cohort study in a normal population

  • Carlo Salustri

      Affiliations

    • Institute of Cognitive Sciences and Technologies (CNR), Fatebenefratelli Hospital, Isola Tiberina, 00186 Rome, Italy
    • Corresponding Author InformationCorresponding author. Address: Istituto di Scienze e Tecnologie della Cognizione – CNR, Unità MEG – Ospedale Fatebenefratelli, Isola Tiberina, 00186 Roma, Italy. Tel.: +39 06 6837 382, +39 06 6837 546; fax: +39 06 6837 360.
  • ,
  • Giulia Barbati

      Affiliations

    • AFaR, Dept. of Neuroscience, Fatebenefratelli Hospital, Isola Tiberina, 00186 Rome, Italy
  • ,
  • Roberta Ghidoni

      Affiliations

    • NeuroBioGen Lab – Memory Clinic, IRCCS “Centro San Giovanni di Dio – Fatebenefratelli”, 25100 Brescia, Italy
  • ,
  • Livia Quintiliani

      Affiliations

    • AFaR, Dept. of Neuroscience, Fatebenefratelli Hospital, Isola Tiberina, 00186 Rome, Italy
  • ,
  • Sofia Ciappina

      Affiliations

    • Scuola Superiore di Psicologia Applicata “G.Sergi”, Palmi (RC), Italy
  • ,
  • Giuliano Binetti

      Affiliations

    • NeuroBioGen Lab – Memory Clinic, IRCCS “Centro San Giovanni di Dio – Fatebenefratelli”, 25100 Brescia, Italy
  • ,
  • Rosanna Squitti

      Affiliations

    • AFaR, Dept. of Neuroscience, Fatebenefratelli Hospital, Isola Tiberina, 00186 Rome, Italy

,Accepted 10 November 2009.

References 

  1. Abe A, Yamashita S, Noma A. Sensitive, direct colorimetric assay for copper in serum. Clin Chem. 1989;35:552–554
  2. Aston-Jones G, Rajkowski J, Cohen J. Role of locus coeruleus in attention and behavioral flexibility. Biol Psychiatry. 1999;46:1309–1320
  3. Babiloni C, Cassetta E, Binetti G, Tombini M, Del Percio C, Ferreri F, et al. Resting EEG sources correlate with attentional span in mild cognitive impairment and Alzheimer’s disease. Eur J Neurosci. 2007;25(12):3742–3757
  4. Babiloni C, Squitti R, Del Percio C, Cassetta E, Ventriglia MC, Ferreri F, et al. Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer’s disease subjects. Clin Neurophysiol. 2007;118:1244–1260
  5. Berridge CW, Waterhouse BD. The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Rev. 2003;42(1):33–84
  6. Bielli P, Calabrese L. Structure to function relationships in ceruloplasmin: a ‘moonlighting’ protein. Cell Mol Life Sci. 2002;59:1413–1427
  7. Binetti G, Magni E, Padovani A, Cappa SF, Bianchetti A, Trabucchi M. Executive dysfunction in early Alzheimer’s disease. Neurol Neurosurg Psychiatry. 1996;60(1):91–93
  8. Bouret S, Sara SJ. Reward expectation, orientation of attention and locus coeruleus-medial frontal cortex interplay during learning. Eur J Neurosci. 2004;20:791–802
  9. Brewer GJ. Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer’s disease. Exp Biol Med. 2007;232(2):323–335[Review]
  10. Bush AI, Strozyk D. Serum copper: a biomarker for Alzheimer disease?. Arch Neurol. 2004;61(5):631–632
  11. Bush AI, Tanzi RE. Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics. 2008;5(3):421–432[Review]
  12. Chutkow JG. Evidence for uptake of nonceruloplasminic copper in the brain: effect of ionic copper and amino acids. Proc Soc Exp Biol Med. 1978;158:113–116
  13. Clemente C, Russo F, Caruso MG, Giangrande M, Fanizza G, Di Leo A. Ceruloplasmin serum level in post-menopausal women treated with oral estrogens administered at different times. Horm Metab Res. 1992;24(4):191–193
  14. Cobb, S. Awareness, attention & physiology of the brain stem. In: Proc Ann Meet Am Psychopathol Assoc. p. 194–204.
  15. Coull JT. Pharmacological manipulations of the alpha 2-noradrenergic system. Effects on cognition. Drugs Aging. 1994;5(2):116–126
  16. Coull JT, Büchel C, Friston KJ, Frith CD. Noradrenergically mediated plasticity in a human attentional neuronal network. Neuroimage. 1999;10(6):705–715
  17. Dietrich AM, Glindemann D, Pizarro F, Gidi V, Olivares M, Araya M, et al. Health and aesthetic impacts of copper corrosion on drinking water. Water Sci Technol. 2004;49(2):55–62
  18. Floyd RA, Carney JM. The role of metal ions in oxidative processes and aging. Toxicol Ind Health. 1993;9(1–2):197–214
  19. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198
  20. Frota NAF, Caramelli P, Barbosa ER. Cognitive impairment in Wilson’s disease. Dementia & Neurophychologia 2009;3(1):16–21.
  21. Galbraith GC, Olfman DM, Huffman TM. Selective attention affects human brain stem frequency-following response. Neuroreport. 2003;14(5):735–738
  22. González C, Martín T, Cacho J, Breñas MT, Arroyo T, García-Berrocal B, et al. Serum zinc, copper, insulin and lipids in Alzheimer’s disease epsilon 4 apolipoprotein E allele carriers. Eur J Clin Invest. 1999;29:637–642
  23. Grant WB, Campbell A, Itzhaki RF, Savory J. The significance of environmental factors in the etiology of Alzheimer’s disease. J Alzheimers Dis. 2002;4(3):179–189
  24. Hoormann J, Falkenstein M, Hohnsbein J. Effects of spatial attention on the brain stem frequency-following potential. Neuroreport. 2004;15(10):1539–1542
  25. Kessler H, Pajonk FG, Meisser P, Schneider-Axmann T, Hoffmann KH, Supprian T, et al. Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer’s disease. J Neural Transm. 2006;113:1763–1769
  26. Lam PK, Kritz-Silverstein D, Barrett Connor E, Milne D, Nielsen F, Gamst A, et al. Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study. J Nutr Health Aging. 2008;12(1):22–27
  27. Lang C. Is Wilson’s disease a dementing condition?. J Clin Exp Neuropsychol. 1989;11:569–570
  28. Le Merrer J, Noguès X. Cognitive neuropharmacology: new perspectives for the pharmacology of cognition. Pharmacol Res. 2000;41(5):503–514[Review]
  29. Lee HJ, Youn JM, O MJ, Gallagher M, Holland PC. Role of substantia nigra–amygdala connections in surprise-induced enhancement of attention. J Neurosci. 2006;26(22):6077–6081
  30. Lezak MD. Domains of behavior from a neuropsychological perspective: the whole story. Nebr Symp Motiv. 1994;41:23–55[Review]
  31. Linder MC, Bryant RR, Lim S, Scott LE, Moor JE. Ceruloplasmin elevation and synthesis in rats with transplantable tumors. Enzyme. 1979;24:85–95
  32. Medalia A, Isaacs-Glaberman K, Scheinberg IH. Neuropsychological impairment in Wilson’s disease. Arch Neurol. 1988;45:502–504
  33. Morris MC, Evans DA, Tangney CC, Bienias JL, Schneider JA, Wilson RS, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol. 2006;63(8):1085–1088
  34. Multhaup G, Masters CL. Metal binding and radical generation of proteins in human neurological diseases and aging. Met Ions Biol Syst. 1999;36:365–387[Review]
  35. Ozcankaya R, Delibas N. Malondialdehyde, superoxide dismutase, melatonin, iron, copper and zinc blood concentrations in patients with Alzheimer disease: cross-sectional study. Croat Med J. 2002;43:28–32
  36. Portala K, Levander S, Westermark K, Ekselius L, von Knorring L. Pattern of neuropsychological deficits in patients with treated Wilson’s disease. Eur Arch Psychiatr Clin Neurosci. 2001;251:262–268
  37. Sedighi B, Shafa MA, Shariati M. A study of serum copper and ceruloplasmin in Alzheimer’s disease in Kerman, Iran. Neurol Asia. 2006;11:107–109
  38. Seniow J, Bak T, Gajda J, Poniatowska R, Czlonkowska A. Cognitive functioning in neurologically symptomatic and symptomatic forms of Wilson’s disease. Mov Disord. 2002;17:1077–1083
  39. Sinha S, Christopher R, Arunodaya GR, Prashanth LK, Gopinath G, Swamy HS, et al. Is low serum to copherol in Wilson’s disease a significant symptom?. J Neurol Sci. 2005;228:121–123
  40. Snaedal J, Kristinsson J, Gunnarsdóttir S, Olafsdóttir A, Baldvinsson M, Jóhannesson T. Copper, ceruloplasmin and superoxide dismutase in patients with Alzheimer’s disease. A case-control study. Dement Geriatr Cogn Disord. 1998;9:239–242
  41. Spinnler H, Dall’Ora P. On Alzheimer’s disease: an overview of diagnostic and research issues for the clinical neurologist. Funct Neurol. 1987;2(1):5–36
  42. Squitti R, Salustri C. Agents complexing copper as a therapeutic strategy for the treatment of Alzheimer’s disease. Curr Alzheimer Res. 2009;6(6):476–487
  43. Squitti R, Lupoi D, Pasqualetti P, Dal Forno G, Vernieri F, Chiovenda P, et al. Elevation of serum copper levels in Alzheimer’s disease. Neurology. 2002;59:1153–1161
  44. Squitti R, Pasqualetti P, Dal Forno G, Moffa F, Cassetta E, Lupoi D, et al. Excess of serum copper not related to ceruloplasmin in Alzheimer disease. Neurology. 2005;64:1040–1046
  45. Squitti R, Barbati G, Rossi L, Ventriglia M, Dal Forno G, Cesaretti S, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau. Neurology. 2006;67:76–82
  46. Uriu-Adams JY, Keen CL. Copper, oxidative stress, and human health. Mol Aspects Med. 2005;26(4–5):268–298[Review]
  47. Wilson SAK. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912;34:295–507
  48. Wolf PL. Ceruloplasmin: methods and clinical use. Crit Rev Clin Lab Sci. 1982;17:229–245
  49. Zatta P, Drago D, Zambenedetti P, Bolognin S, Nogara E, Peruffo A, et al. Accumulation of copper and other metal ions, and metallothionein I/II expression in the bovine brain as a function of aging. J Chem Neuroanat. 2008;[Epub ahead of print]
  50. Zecca L, Stroppolo A, Gatti A, Tampellini D, Toscani M, Gallorini M, et al. The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. Proc Natl Acad Sci USA. 2004;101(26):9843–9848

PII: S1388-2457(09)00785-8

doi: 10.1016/j.clinph.2009.11.090

Clinical Neurophysiology
Volume 121, Issue 4 , Pages 502-507 , April 2010