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DNA damage, copper and lead associates with cognitive function among older adults

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The journal of nutrition, health & aging

Abstract

Background

A cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage.

Method

Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.

Results

A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).

Conclusion

High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.

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References

  1. United Nations Department of Economic and Social Affairs Population Division. (2013) World Population Ageing 2013. Demographic Determinants and Speed of Population Ageing, vol 2013. New York, New York

    Google Scholar 

  2. Swerdlow RH. The neurodegenerative mitochondriopathies. J Alzheimers Dis 2009;17(4):737–751. doi:10.3233/JAD-2009-1095 5710604376T63540 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Deary IJ, Corley J, Gow AJ, Harris SE, Houlihan LM, Marioni RE, Penke L, Rafnsson SB, Starr JM. Age-associated cognitive decline. British Medical Bulletin 2009;92(1):135–152. doi:10.1093/bmb/ldp033

    Article  PubMed  Google Scholar 

  4. Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nature Reviews Neuroscience 2006;7:278–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Meramat A, Rajab NF, Shahar S, Sharif R. Cognitive impairment, genomic instability and trace elements. The journal of nutrition, health & aging: 2014;1-10. doi:10.1007/s12603-014-0489-1

    Google Scholar 

  6. Lovell MA, Markesbery WR. Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease. Nucleic Acids Research 2007;35(22):7497–7504. doi:10.1093/nar/gkm821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. Journal of Neurochemistry 2005;93(4):953–962. doi:10.1111/j.1471-4159.2005.03053.x

    Article  CAS  PubMed  Google Scholar 

  8. Desport JC, Couratier P. Stress oxydant et maladies neuro-de´ge´ne´ ratives. clinical nutrition and metabolic 2002;16:253–260

    Article  CAS  Google Scholar 

  9. McDaniel MA, Maier SF, Einstein GO. “Brain-specific” nutrients: a memory cure? Nutrition (Burbank, Los Angeles County, Calif) 2003;19(11):957–975

    Article  CAS  Google Scholar 

  10. Smorgon C, Mari E, Atti AR, Dalla Nora E, Zamboni PF, Calzoni F, Passaro A, Fellin R. Trace elements and cognitive impairment: an elderly cohort study. Archives of gerontology and geriatrics Supplement 2004;(9):393–402

    Article  CAS  Google Scholar 

  11. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. Journal of the American Geriatrics Society 2005;53(4):695–699. doi:10.1111/j.1532-5415.2005.53221.x

    Article  PubMed  Google Scholar 

  12. Razali R, Jean-Li L, Jaffar A, Ahmad M, Shah SA, Ibrahim N, Din NC, Jaafar NR, Midin M, Sidi H, Ahmad S. Is the Bahasa Malaysia version of the Montreal Cognitive Assessment (MoCA-BM) a better instrument than the Malay version of the Mini Mental State Examination (M-MMSE) in screening for mild cognitive impairment (MCI) in the elderly? Comprehensive psychiatry 2014;55(1):70–75

    Article  Google Scholar 

  13. Rodushkin I, Axelsson MD. Application of double focusing sector field ICP-MS for multielemental characterization of humanhair and nails. Part I. Analytical methodology. Science of the Total Environment 2000;250(1–3):83–100

    Article  CAS  PubMed  Google Scholar 

  14. Chen K-L, Amarasiriwardena C, Christiani D. Determination of total arsenic concentrations in nails by inductively coupled plasma mass spectrometry. Biological Trace Element Research 1999;67(2):109–125. doi:10.1007/BF02784067

    Article  CAS  PubMed  Google Scholar 

  15. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research 1988;175(1):184–191. doi:http://dx.doi.org/10.1016/0014-4827(88)90265-0

    Article  CAS  PubMed  Google Scholar 

  16. Beyer WFJ, Fridovich I. Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Analytical Biochemistry 1987;161(2):559–566

    Article  CAS  PubMed  Google Scholar 

  17. Stocks J, Gutteridge JM, Sharp RJ, Dormandy TL. Assay using brain homogenate for measuring the antioxidant activity of biological fluids. Clinical Science and molecular medicine 1974;47(3):215–222

    CAS  PubMed  Google Scholar 

  18. Goullé JP, Saussereau E, Mahieu L, Bouige D, Groenwont S, Guerbet M, Lacroix C. Application of Inductively Coupled Plasma Mass Spectrometry Multielement Analysis in Fingernail and Toenail as a Biomarker of Metal Exposure. Journal of Analytical Toxicology 2009;33(2):92–98. doi:10.1093/jat/33.2.92

    Article  PubMed  Google Scholar 

  19. Ghazali AR, Kamarulzaman F, Normah C, Ahmad M, Ghazali S, Ibrahim N, Said Z, Shahar S, Angkat N, Razali R. Levels of Metallic Elements and Their Potential Relationships to Cognitive Function among Elderly from Federal Land Development Authority (FELDA) Settlement in Selangor Malaysia. Biological Trace Element Research 2013;153(1–3):16–21. doi:10.1007/s12011-013-9642-7

    Article  CAS  PubMed  Google Scholar 

  20. Freitas S, Simões MR, Marôco J, Alves L, Santana I. Construct Validity of the Montreal Cognitive Assessment (MoCA). Journal of the International Neuropsychological Society 2012;18(02):242–250. doi:doi:10.1017/S1355617711001573

    Article  PubMed  Google Scholar 

  21. Hoops S, Nazem S, Siderowf AD, Duda JE, Xie SX, Stern MB, Weintraub D. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 2009;73(21):1738–1745. doi:10.1212/WNL.0b013e3181c34b47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Valenzuela M, Brayne C, Sachdev P, Wilcock G, Function FMoBotMRCC, Study A. Cognitive Lifestyle and Long-Term Risk of Dementia and Survival After Diagnosis in a Multicenter Population-based Cohort. American Journal of Epidemiology 2011;173(9):1004–1012. doi:10.1093/aje/kwq476

    Article  PubMed  Google Scholar 

  23. Sharp ES, Gatz M. The Relationship between Education and Dementia An Updated Systematic Review. Alzheimer disease and associated disorders 2011;25(4):289–304. doi:10.1097/WAD.0b013e318211c83c

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tosi A, Piraccini B. Biology of nail, vol 5. New York, 1999

    Google Scholar 

  25. Gao S, Jin Y, Unverzagt FW, Ma F, Hall KS, Murrell JR, Cheng Y, Shen J, Ying B, Ji R, Matesan J, Liang C, Hendrie HC. Trace element levels and cognitive function in rural elderly Chinese. Journals of Gerontology-Series A Biological Sciences and Medical Sciences 2008;63(6):635–641

    Article  Google Scholar 

  26. Mocchegiani E, Bertoni-Freddari C, Marcellini F, Malavolta M. Brain, aging and neurodegeneration: Role of zinc ion availability. Progress in Neurobiology 2005;75(6):367–390. doi:http://dx.doi.org/10.1016/j.pneurobio.2005.04.005

    Article  CAS  PubMed  Google Scholar 

  27. Sfar S, Jawed A, Braham H, Amor S, Laporte F, Kerkeni A. Zinc, copper and antioxidant enzyme activities in healthy elderly Tunisian subjects. Experimental Gerontology 2009;44(12):812–817. doi:http://dx.doi.org/10.1016/j.exger.2009.10.008

    Article  CAS  PubMed  Google Scholar 

  28. Watt NT, Whitehouse IJ, Hooper NM. The Role of Zinc in Alzheimer’s Disease. International Journal of Alzheimer&#x2019;s Disease 2011:10. doi:10.4061/2011/971021

    Google Scholar 

  29. Rahmann H, Rahmann M. Chemical Aspects of Neuronal Information Transmission in Synapses. In: Rahmann H, Rahmann M (eds) The Neurobiological Basis of Memory and Behavior. Springer-Verlag New York, New York, p 163

  30. Tonkikh A, Janus C, El-Beheiry H, Pennefather PS, Samoilova M, McDo, 2012nald P, Ouanounou A, Carlen PL. Calcium chelation improves spatial learning and synaptic plasticity in aged rats. Experimental Neurology 2006;197(2):291–300. doi:http://dx.doi.org/10.1016/j.expneurol.2005.06.014

    Article  CAS  PubMed  Google Scholar 

  31. Khalil N, Morrow LA, Needleman H, Talbott EO, Wilson JW, Cauley JA. Association of Cumulative Lead and Neurocognitive Function in an Occupational Cohort. Neuropsychology 2009;23(1):10–19

    Article  PubMed  Google Scholar 

  32. Dobrowolska J, Dehnhardt M, Matusch A, Zoriy M, Palomero-Gallagher N, Koscielniak P, Zilles K, Becker JS. Quantitative imaging of zinc, copper and lead in three distinct regions of the human brain by laser ablation inductively coupled plasma mass spectrometry. Talanta 2008;74(4):717–723. doi:http://dx.doi.org/10.1016/j. talanta.2007.06.051

    Article  CAS  PubMed  Google Scholar 

  33. Schlief ML, West T, Craig AM, Holtzman DM, Gitlin JD. Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity. Proceedings of the National Academy of Sciences of the United States of America 2006;103(40):14919–14924. doi:10.1073/pnas.0605390103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hung YH, Robb EL, Volitakis I, Ho M, Evin G, Li Q-X, Culvenor JG, Masters CL, Cherny RA, Bush AI. Paradoxical Condensation of Copper with Elevated β-Amyloid in Lipid Rafts under Cellular Copper Deficiency Conditions: IMPLICATIONS FOR ALZHEIMER DISEASE. The Journal of Biological Chemistry 2009;284(33):21899–21907. doi:10.1074/jbc.M109.019521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bandeen-Roche K, Glass TA, Bolla K, Todd AC, Schwartz BS. Cumulative lead dose and cognitive function in older adults. Epidemiology 2009;20(6):831–839

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 2003;126(1):5–19

    Article  PubMed  Google Scholar 

  37. Ramesh GT, Manna SK, Aggarwal BB, Jadhav AL. Lead exposure activates nuclear factor kappa B, activator protein-1, c-Jun N-terminal kinase and caspases in the rat brain. Toxicology Letters 2001;123(2–3):195–207. doi:http://dx.doi.org/10.1016/S0378-4274(01)00395-2

    Article  CAS  PubMed  Google Scholar 

  38. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Current Neuropharmacology 2009;7(1):65–74. doi:10.2174/157015909787602823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schuessel K, Leutner S, Cairns NJ, Müller WE, Eckert A. Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer’s disease brain. Journal of Neural Transmission 2004;111(9):1167–1182. doi:10.1007/s00702-004-0156-5

    Article  CAS  PubMed  Google Scholar 

  40. Sultana R, Reed T, Butterfield DA. Redox Proteomics and Metabolic Proteins in Brain of Subjects with Alzheimer’s Disease, Mild Cognitive Impairment, and Models Thereof. In: Neural Degeneration and Repair. Wiley-VCH Verlag GmbH & Co. KGaA, 2008;pp 181–207. doi:10.1002/9783527622467.ch9

    Chapter  Google Scholar 

  41. Lee LK, Shahar S, Rajab N. Serum folate concentration, cognitive impairment, and DNA damage among elderly individuals in Malaysia. Nutrition Research 2009;29(5):327–334. doi:http://dx.doi.org/10.1016/j.nutres.2009.05.006

    Article  CAS  PubMed  Google Scholar 

  42. Simpson JE, Ince PG, Matthews FE, Shaw PJ, Heath PR, Brayne C, Garwood C, Higginbottom A, Wharton SB, Function MRCC, Ageing Neuropathology Study G. A neuronal DNA damage response is detected at the earliest stages of Alzheimer’s neuropathology and correlates with cognitive impairment in the MRC-CFAS ageing brain cohort. Neuropathology and Applied Neurobiology:n/a-n/a. 2014;doi:10.1111/nan.12202

    Google Scholar 

  43. Mulware SJ. Trace elements and carcinogenicity: a subject in review. 3 Biotech 2013;3(2):85–96. doi:10.1007/s13205-012-0072-6

    Article  PubMed  Google Scholar 

  44. Dreosti IE. Free Radical Pathology and The Genome. In: Dreosti IE (ed) Trace Elements, Micronutrients, and Free Radicals. Humana Press Inc, New York, 2012;pp 149–169

    Google Scholar 

  45. Brezova V, Valko M, Breza M, Morris H, Telser J, Dvoranova D, Kaiserova K, Varecka L, Mazur M, Leibfritz. Role of Radicals and Singlet Oxygen in Photoactivated DNA Cleavage by the Anticancer Drug Camptothecin: An Electron Paramagnetic Resonance Study. The Journal of Physical Chemistry B 2003;107(10):2415–2425. doi:10.1021/jp027743m

    Article  CAS  Google Scholar 

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Correspondence to Razinah A. Sharif.

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Meramat, A., Rajab, N.F., Shahar, S. et al. DNA damage, copper and lead associates with cognitive function among older adults. J Nutr Health Aging 21, 539–545 (2017). https://doi.org/10.1007/s12603-016-0759-1

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  • DOI: https://doi.org/10.1007/s12603-016-0759-1

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