Abstract
Introduction. Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s disease (AD), so identification of the related risk factors can be helpful. There are controversial data regarding the serum oxidant/antioxidant status, trace elements and homocysteine (Hcy) as effective parameters in this disease, therefore the status of these factors was determined in this study.
Methods. One hundred-twenty elderly persons with cognitive impairment and 120 elderly healthy persons who were differentiated using Mini-mental state examination (MMSE) participated in this study. The patients were divided into mild and moderate-to-severe cognitive impairment group. Serum antioxidant/oxidant, copper (Cu), manganese (Mn), zinc (Zn) and Hcy concentrations were measured using routine methods.
Results. Oxidant and antioxidant levels increased and decreased based on the severity of the disease and were higher and lower in patients than in control group, respectively (p<0.001). With adjusting for age, gender and education, significant difference in Hcy levels was not observed. There was no significant difference in trace elements levels among groups.
Conclusions. Results confirmed the association between oxidative damage with increasing the severity of cognitive impairment. These factors may be involved in the etiology of cognitive impairment and AD. Identification of such biomarkers is important to select appropriate treatment goals before the onset of irreversible clinical signs.
– Alzheimer’s disease
– mild cognitive impairment
– oxidative stress
– amyloid-β
– malondialdehyde
– Thiobarbituric Acid Reactive Substances
– Ferric Reduction Antioxidant Power
– Homocysteine
– Mini-Mental State Examination
– mild cognitive impairment stage I
– mild cognitive impairment stage II and III or moderate to severe cognitive impairment
– Amirkola Health and Aging Project
REFERENCES
1. BURNS A, ZAUDIG M. Mild cognitive impairment in older people. Lancet 2002; 360(9349):1963-1965.
2. AKSENOV MY, AKSENOVA MV, BUTTERFIELD DA. Protein oxidation in the brain in Alzheimer’s disease. Neuroscience 2001; 103(2):373-383.
3. BUTTERFIELD DA, CM LAUDERBACK. Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002; 32(11):1050-1060.
4. LI JC, KAMINSKAS E. Deficient repair of DNA lesions in alzheimer’s disease fibroblasts. Biochem Biophys Res Commun 1985; 129(3):733-738.
5. SAYRE LM, ZELASKO DA, HARRIS PL. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer’s disease. J Neurochem 1997; 68(5):2092-2097.
6. HARDY J, ALLSOP D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 1991; 12:383-388.
7. ZHANG YW, THOMPSON R, ZHANG H. APP processing in Alzheimer’s disease. Mol Brain 2011; 4(1):3.
8. DYRKS T, DYRKS E, HARTMANN T. Amyloidogenicity of beta A4 and beta A4-bearing amyloid protein precursor fragments by metal-catalyzed oxidation. J Biol Chem 1992; 267(25):18210-17.
9. K HENSLEY, JM CARNEY, MP MATTSON. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci 1994; 91(8):3270-3274.
10. BUTTERFIELD DA, HENSLEY K, HARRIS M. β-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: Implications to Alzheimer’s disease. Biochem Biophys Res Commun 1994; 200(2):710-715.
11. NUNOMURA A, PERRY G, ALIEV G, HIRAI K, TAKEDA A, BALRAJ EK et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001; 60(8):759-767.
12. NUNOMURA A, CHIBA S, LIPPA CF, CRAS P, KALARIA RN, TAKEDA A et al. Neuronal RNA oxidation is a prominent feature of familial Alzheimer’s disease. Neurobiol Dis 2004; 17(1):108-113.
13. MOREIRA PI, SANTOS MS, OLIVEIRA CR, SHENK JC, NUNOMURA A, SMITH MA et al. Alzheimer disease and the role of free radicals in the pathogenesis of the disease. CNS Neurol Disord Drug Targets 2008; 7(1):3-10.
14. KONTUSH A, BERNDT C, WEBER W, AKOPYAN V, ARLT S, SCHIPPLING S et al. Amyloid-β is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radic Biol Med 2001; 30(1):119-128.
15. 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(1):47-52.
16. Castellani RJ, Rolston RK, Smith MA. Alzheimer disease. Dis Mon 2010; 56(9):484.
17. RAMOS MI, ALLEN LH, MUNGAS DM, JAGUST WJ, HAAN MN, GREEN R et al. Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005; 82(6):1346-1352.
18. QUADRI P, FRAGIACOMO C, PEZZATI R, ZANDA E, FORLONI G, TETTAMANTI M et al. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr 2004; 80(1):114-122.
19. TUCKER KL, QIAO N, SCOTT T, ROSENBERG I, SPIRO A. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr 2005; 82(3):627-635.
20. MILLER, A.L. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 2003; 8(1):7-19.
21. BOLDYREV A. Molecular mechanisms of homocysteine toxicity and possible protection against hyperhomocysteinemia. Recent advances on nutrition and the prevention of Alzheimer’s disease. Trivandrum, India: Transworld Research Network 2010; 127-43.
22. HOSSEINI SR, CUMMING RG, KHEIRKHAH F, NOOREDDINI H, BAJANI M, MIKANIKI E et al. Cohort profile: The Amirkola health and ageing project (AHAP). Int J Epidemiol 2014; 43(5):1393-400
23. PETERSEN RC, NEGASH S. Mild cognitive impairment: an overview. CNS Spectr 2008; 13(1):45.
24. PRICE JL, KO AI, WADE MJ, TSOU SK, MCKEEL DW, MORRIS JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol 2001; 58(9):1395-1402.
25. GRAY SL, HANLON JT, LANDERMAN LR, ARTZ M, SCHMADER KE, FILLENBAUM GG. Is antioxidant use protective of cognitive function in the community-dwelling elderly? Am J Geriatr Pharmacother 2003; 1(1): 3-10.
26. MAYNARD CJ, BUSH AI, MASTERS CL, CAPPAI R, LI QX. Metals and amyloid-β in Alzheimer’s disease. Int J Exp Pathol 2005; 86(3):147-159.
27. MASSIE HR, AIELLO VR, IODICE AA. Changes with age in copper and superoxide dismutase levels in brains of C57BL/6J mice. Mech Ageing Dev 1979; 10(1):93-99.
28. MAYNARD CJ, CAPPAI R, VOLITAKIS I, CHERNY RA, WHITE AR, BEYREUTHER K et al. Overexpression of Alzheimer’s disease amyloid-β opposes the age-dependent elevations of brain copper and iron. J Biol Chem 2002; 277(47):44670-44676.
29. ROOS PM, VESTERBERG O, NORDBERG M. Metals in motor neuron diseases. Exp Biol Med (Maywood) 2006; 231(9):1481-1487.
30. HA C, RYU J, PARK CB. Metal ions differentially influence the aggregation and deposition of Alzheimer’s β-amyloid on a solid template. Biochemistry 2007; 46(20):6118-6125.
31. ZUCCONI GG, CIPRIANI S, SCATTONI R, BALGKOURANIDOU I, HAWKINS DP, RAGNARSDOTTIR KV. Copper deficiency elicits glial and neuronal response typical of neurodegenerative disorders. Neuropathol Appl Neurobiol 2007; 33(2):212-225.
32. LUTSENKO S, BARNES NL, BARTEE MY, DMITRIEV OY. Function and regulation of human copper-transporting ATPases. Physiol Rev 2007; 87(3):1011-1046.
33. TAYLOR JP, HARDY J, FISCHBECK KH. Toxic proteins in neurodegenerative disease. Science 2002; 296(5575):1991-1995.
34. GOLBAHAR J, BARARPOUR H. Normal range of total plasma homocysteine concentrations in southern Iran. IJMS 2003; 28:139-42.
35. COLLABORATION H.S. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288(16):2015-2022.
36. TEMPLE ME, LUZIER AB, KAZIERAD DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 2000; 34(1):57-65.
37. ZHAO L, YAN Y, WANG Y, CAI Z. Homocysteine Contributes to Pathogenesis by Oxidative stress for Alzheimer’s disease. Aging and Neurodegeneration 2013; 1:1.