Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

1 Issue per year


IMPACT FACTOR 2016 (Open Life Sciences): 0.448

CiteScore 2016: 1.02

SCImago Journal Rank (SJR) 2016: 0.329
Source Normalized Impact per Paper (SNIP) 2016: 0.621

Open Access
Online
ISSN
2391-5412
See all formats and pricing
More options …
Volume 2, Issue 1 (Mar 2007)

Issues

Effect of homocysteine and nitric oxide levels on specific Computed Axial Tomography measurements in Alzheimer disease

Silvia Baiguera / Maurizio Gallucci / Andrea Zanardo / Marcella Folin
Published Online: 2007-01-26 | DOI: https://doi.org/10.2478/s11535-007-0002-5

Abstract

The present study was undertaken to examine the effect of Homocysteine (Hcy) and nitric oxide (NO) levels on specific Computed Axial Tomography (CAT) measurements, as global brain atrophy and brain vascular lesion in Alzheimer Disease (AD) and in Vascular Dementia (VD) patients. We have analysed serum Hcy and NO levels in AD patients and compared the findings with those in VD patients and control subjects. Moreover we have studied the correlation of Hcy and NO levels with cognitive impairment and brain atrophy determined by Computed Axial Tomography. Hcy serum levels significantly increased in all demented patients compared to control group, independently from the dementia type. On the contrary, no differences were observed in NO serum levels between groups. Moreover, we found significant correlation between Hcy and brain atrophy in both demented groups; whereas NO levels correlated only in AD, but not in VD patients. The pathogenic effect of Hcy either in AD and VD patients appears to confirm a definitive vascular component in AD. As regards NO, our results highlight the role of NO as a beneficial molecule in AD and support the use of NO mimetics as an antineurodegenerative therapy for AD patients.

Keywords: Alzheimer disease; brain atrophy; cognitive impairment; homocysteine; neuroimaging; nitric oxide; vascular dementia

  • [1] E. Englund, A. Brun and L. Gustafson: “A white-matter disease in dementia of Alzheimer type. Clinical and neuropathological correlates”, Int. J. Ger. Psych., Vol. 4, (1989), pp. 87–102. http://dx.doi.org/10.1002/gps.930040207CrossrefGoogle Scholar

  • [2] M.L. Selley: “Increased concentrations of homocysteine and asymmetric dimethyl arginine and dicreased concentrations of nitric oxide in the plasma of patience with Alzhemier’s disease”, Neurobiol. Aging, Vol. 24, (2003), pp. 903–907. http://dx.doi.org/10.1016/S0197-4580(03)00007-1CrossrefGoogle Scholar

  • [3] R. Diaz-Arrastia: “Homocysteine and neurologic disease”, Arch. Neurol., Vol. 57, (2000), pp. 1422–1427. http://dx.doi.org/10.1001/archneur.57.10.1422CrossrefGoogle Scholar

  • [4] N.D. Prins, T. den Heijer, A. Hofman, P.J. Koudstaal, J. Jolles, R. Clarke and M.M. Breteler: “Homocysteine and cognitive function in the elderly. The Rotterdam Scan Study”, Neurology, Vol. 59, (2002), pp. 1375–1380. CrossrefGoogle Scholar

  • [5] G. Ravaglia, P. Forti, F. Maioli, A. Muscari, L. Sacchetti, G. Arnone, V. Nativio, T. Talerico and E. Mariani: “Homocysteine and cognitive function in healthy elderly community dwellers in Italy“, Am. J. Clin. Nutr., Vol. 77, (2003), pp. 668–673. Google Scholar

  • [6] K.M. Riggs, A. Spiro 3rd, K. Tucker and D. Rush: “Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study”, Am. J. Clin. Nutr., Vol. 63, (1996), pp. 306–314. Google Scholar

  • [7] S. Seshadri, A. Beiser, J. Selhub, P.F. Jacques, I.H. Rosenberg, R.B. D’Agostino, P.W. Wilson and P.A. Wolf: “Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease”, N. Engl. J. Med., Vol. 346, (2002), pp. 476–483. http://dx.doi.org/10.1056/NEJMoa011613CrossrefGoogle Scholar

  • [8] A. McCaddon, G. Davies, P. Hudson, S. Tandy and H. Cattel: “Total serum homocysteine in senile dementia of Alzheimer type”, Int. J. Ger. Psych., Vol. 13, (1998), pp. 235–239. http://dx.doi.org/10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8CrossrefGoogle Scholar

  • [9] R. Clarke, A.D. Smith, K.A. Jobst, H. Refsum, L. Sutton and P.M. Ueland: “Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease”, Arch. Neurol., Vol. 55, (1998), pp. 1449–1455. http://dx.doi.org/10.1001/archneur.55.11.1449CrossrefGoogle Scholar

  • [10] P. Quadri, C. Fragiacomo, R. Pezzati, E. Zanda, G. Forloni, M. Tettamanti and U. Lucca: “Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia”, Am. J. Clin. Nutr., Vol. 80, (2004), pp. 114–122. Google Scholar

  • [11] G. Ravaglia, P. Forti, F. Maioli, M. Martelli, L. Servadei, N. Brunetti, E. Porcellini and F. Licastro: “Homocysteine and folate as risk factors for dementia and Alzheimer disease“, Am. J. Clin. Nutr., Vol. 82, (2005), pp. 636–643. Google Scholar

  • [12] J.A. Luchsinger, M.X. Tang, S. Shea, J. Miller, R. Green and R. Mayeux: “Plasma homocysteine levels and risk of Alzheimer disease”, Neurology, Vol. 62, (2004), pp. 1972–1976. CrossrefGoogle Scholar

  • [13] M. Folin, S. Baiguera, M. Gallucci, M.T. Conconi, R. Di Liddo, A. Zanardo and P.P. Parnigotto: “A Cross-sectional Study of Homocysteine-, NO-levels, and CT-findings in Alzheimer Dementia, Vascular Dementia and Controls”, Biogerontology, Vol. 6, (2005), pp. 255–260. http://dx.doi.org/10.1007/s10522-005-2622-3CrossrefGoogle Scholar

  • [14] J.P. Cooke and V.J. Dzau: “Nitric oxide synthase: role in the genesis of vascular disease”, Annu. Rev. Med., Vol. 48, (1997), pp. 489–509. http://dx.doi.org/10.1146/annurev.med.48.1.489CrossrefGoogle Scholar

  • [15] J.C. de la Torre and G.B. Stefano: “Evidence that Alzheimer’s disease is a microvascular disorder: the role of constitutive nitric oxide”, Brain Res. Rev., Vol. 34, (2000), pp. 119–136. http://dx.doi.org/10.1016/S0165-0173(00)00043-6CrossrefGoogle Scholar

  • [16] E. Tarkowski, A. Ringqvist, K. Blennow, A. Wallin and A. Wennmalm: “Intrathecal release of nitric oxid in Alzheimer’s disease and vascular dementia”, Dement. Geriatr. Cogn. Disord., Vol. 11, (2000), pp. 322–326. http://dx.doi.org/10.1159/000017261CrossrefGoogle Scholar

  • [17] G.C. Roman, T.K. Tatemichi, T. Erkinjuntti, J.L. Cummings, J.L. Masdeu, J.H. Garcia, L. Amaducci, J.M. Orgogozo, A. Brun and A. Hofman: “Vascular dementia: Diagnostic criteria for research studies“, Report of the NINDS-ARIEN International workshop, Neurology, Vol. 43, (1993), pp. 250–260. CrossrefGoogle Scholar

  • [18] M.F. Folstein, S.E. Folstein and P.R. McHugh: “Mini-Mental State” A practical method for grading the cognitive state of patients for the clinician”, J. Psychiatr. Res., Vol. 12, (1975), pp. 189–198. http://dx.doi.org/10.1016/0022-3956(75)90026-6CrossrefGoogle Scholar

  • [19] G.B. Frisoni, C. Geroldi, A. Beltramello, A. Bianchetti, G. Binetti, G. Bordiga, C. DeCarli, M.P. Laakso, H. Soininen, C. Testa, O. Zanetti and M. Trabucchi: “Radial width of the temporal horn: a sensitive measure in Alzheimer disease”, AJNR Am. J. Neuroradiol., Vol. 23, (2002), pp. 35–47. Google Scholar

  • [20] C. Geroldi, S. Galluzzi, C. Testa, O. Zanetti and G.B. Frisoni “Validation study of a CT-based weighted rating scale for subcortical ischemic vascular disease in patients with mild cognitive deterioration”, Eur. Neurol., Vol. 49, (2003), pp. 193–209. http://dx.doi.org/10.1159/000070183CrossrefGoogle Scholar

  • [21] K. Fassbender, O. Mielke, T. Bertsch, B. Nafe, S. Froschen and M. Hennerici: “Homocysteine in cerebral macroangiography and microangiopathy”, Lancet, Vol. 353, (1999), pp. 1586–1587. http://dx.doi.org/10.1016/S0140-6736(99)00309-8CrossrefGoogle Scholar

  • [22] K.A. Hajjar: “Homocysteine: a sulphrous fire”, J. Clin. Invest., Vol. 107, (2001), pp. 663–664. http://dx.doi.org/10.1172/JCI12369CrossrefGoogle Scholar

  • [23] S.P. McIlroy, K.B. Dynan, J.T. Lawson, C.C. Patterson and A.P. Passmore: “Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland”, Stroke, Vol. 33, (2002), pp. 2351–2356. http://dx.doi.org/10.1161/01.STR.0000032550.90046.38CrossrefGoogle Scholar

  • [24] K. Nilsson, L. Gustafson and B. Hultberg: “Relation between plasma homocysteine and Alzheimer’s disease”, Dement. Geriatr. Cogn. Disord., Vol. 14, (2002), pp. 7–12. http://dx.doi.org/10.1159/000058327CrossrefGoogle Scholar

  • [25] S.A. Lipton, W.K. Kim, Y.B. Choi, S. Kumar, D.M. D’Emilia, P.V. Rayudu, D.R. Arselle and J.S. Stamler: “Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor”, Proc. Natl. Acad. Sci. U. S. A., Vol. 94, (1997), pp. 5923–5928. http://dx.doi.org/10.1073/pnas.94.11.5923CrossrefGoogle Scholar

  • [26] I.I. Krugman, T.S. Kumaravel, A. Lohani, W.A. Pedersen, R.G. Cutler, Y. Kruman, N. Haughey, J. Lee, M. Evans and M.P. Mattson: “Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease”, J. Neurosci., Vol. 22, (2002), pp. 1752–1762. Google Scholar

  • [27] T. den Heijer, S.E. Vermeer, R. Clarke, M. Oudkerk, P.J. Koudstaal, A. Hofman and M.M. Breteler: “Homocysteine and brain atrophy on MRI of non-demented elderly”, Brain, Vol. 126, (2003), pp. 170–175. http://dx.doi.org/10.1093/brain/awg006CrossrefGoogle Scholar

  • [28] P.S. Sachdev, M. Valenzuela, X.L. Wang, J.C. Looi and H. Brodaty: “Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals”, Neurology, Vol. 58, (2002), pp. 1539–1541. CrossrefGoogle Scholar

  • [29] J. Garthwaite, S.L. Charles and R. Chess-Williams: “Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain”, Nature, Vol. 336, (1988), pp. 385–388. http://dx.doi.org/10.1038/336385a0CrossrefGoogle Scholar

  • [30] J.E. Haley, G.L. Wilcox and P.F. Chapman: “The role of nitric oxide in hippocampal long-term potentiation”, Neuron, Vol. 8, (1992), pp. 211–216. http://dx.doi.org/10.1016/0896-6273(92)90288-OCrossrefGoogle Scholar

  • [31] F.M. Faraci: “Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation”, Am. J. Physiol., Vol. 261, (1991), pp. H1038–1042. Google Scholar

  • [32] A. Wallin, C.G. Gottfries, I. Karlsson and L. Svennerholm: “Decreased myelin lipids in Alzheimer’s disease and vascular dementia”, Acta Neurol. Scand., Vol. 80, (1989), pp. 319–323. http://dx.doi.org/10.1111/j.1600-0404.1989.tb03886.xCrossrefGoogle Scholar

  • [33] B.T. Hyman, K. Marzloff, J.J. Wenniger, T.M. Dawson, D.S. Bredt and S.H. Snyder: “Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer’s disease”, Ann. Neurol., Vol. 32, (1992), pp. 311–330. http://dx.doi.org/10.1002/ana.410320618CrossrefGoogle Scholar

  • [34] G.R. Thatcher, B.M. Bennett, H.C. Dringenberg and J.N. Reynolds: “Novel nitrates as NO mimetics directed at Alzheimer’s disease”, J. Alzheimers Dis., Vol. 6, (2004), pp. S75–84. Google Scholar

  • [35] G. Benthin, I. Bjorkhem, O. Breuer, A. Sakinis and A Wennmalm: “Transformation of subcutaneous nitric oxide into nitrite and nitrate in rat”, Biochem. J., Vol. 323, (1997), pp. 853–858. Google Scholar

About the article

Published Online: 2007-01-26

Published in Print: 2007-03-01


Citation Information: Open Life Sciences, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-007-0002-5.

Export Citation

© 2007 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Comments (0)

Please log in or register to comment.
Log in