Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism
Article First Online: 06 July 2005 Received: 18 September 2004 Accepted: 05 May 2005 Summary.
Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p = 0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald χ
2 = 4.071, OR = 1.043, 95% CI 1.001–1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC = 0.68, 95% CI = 0.57–0.79, p = 0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal. Keywords: Homocysteine, alcohol withdrawal, alcoholism, cognition, cognitive decline. References Ahern, KB, Lustig, HS, Greenberg, DA 1994 Enhancement of NMDA toxicity and calcium responses by chronic exposure of cultured cortical neurons to ethanol. Neurosci Lett 165 211 214 PubMed Google Scholar Bell, IR, Edman, JS, Selhub, J, Morrow, FD, Marby, DW, Kayne, HL, Cole, JO 1992 Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand 86 386 390 PubMed Google Scholar Bleich, S, Bandelow, B, Javaheripour, K, Müller, A, Degner, D, Wilhelm, J, Havemann-Reinecke, U, Sperling, W, Rüther, E, Kornhuber, J 2003a Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism. Neurosci Lett 335 179 182 CrossRef Google Scholar Bleich, S, Bayerlein, K, Reulbach, U, Hillemacher, T, Bönsch, D, Mugele, B, Kornhuber, J, Sperling, W 2004a Homocysteine levels in patients classified according to Lesch’s typology. Alcohol 39 493 498 Google Scholar Bleich, S, Carl, M, Bayerlein, K, Reulbach, U, Biermann, T, Hillemacher, T, Bönsch, D, Kornhuber, J 2005 Evidence of increased homocysteine levels in alcoholism: the Franconian Alcoholism Research Studies (FARS). Alcohol Clin Exp Res 29 334 336 PubMed Google Scholar Bleich, S, Degner, D, Bandelow, B, von Ahsen, N, Rüther, E, Kornhuber, J 2000a Plasma homocysteine is a predictor of alcohol withdrawal seizures. Neuroreport 11 2749 2752 Google Scholar Bleich, S, Degner, D, Sperling, W, Bönsch, D, Thürauf, N, Kornhuber, J 2004b Homocysteine as a neurotoxin in chronic alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 28 453 464 CrossRef Google Scholar Bleich, S, Degner, D, Wiltfang, J, Maler, JM, Niedmann, P, Cohrs, S, Mangholz, A, Porzig, J, Sprung, R, Ruther, E, Kornhuber, J 2000b Elevated homocysteine levels in alcohol withdrawal. Alcohol 35 351 354 Google Scholar Bleich, S, Spilker, K, Kurth, C, Degner, D, Quintela-Schneider, M, Javaheripour, K, Rüther, E, Kornhuber, J, Wiltfang, J 2000c Oxidative stress and an altered methionine metabolism in alcoholism. Neurosci Lett 293 171 174 CrossRef Google Scholar Bleich, S, Wiltfang, J, Kornhuber, J 2003b Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 349 609 610 CrossRef Google Scholar Böckelmann, I, Darius, S, McGauran, N, Robra, BP, Peter, B, Pfister, EA 2002 The psychological effects of exposure to mixed organic solvents on car painters. Disabil Rehabil 24 455 461 PubMed Google Scholar Butterworth, RF 1995 Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Metab Brain Dis 10 1 8 PubMed Google Scholar Cravo, ML, Gloria, LM, Selhub, J, Nadeau, MR, Camilo, ME, Resende, MP, Cardoso, JN, Leitao, CN, Mira, FC 1996 Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am J Clin Nutr 63 220 224 PubMed Google Scholar Crews, FT 1999 Alcohol and neurodegeneration. CNS Drug Rev 5 379 394 Google Scholar Frantzen, F, Faaren, AL, Alfheim, I, Nordhei, AK 1998 Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem 44 311 316 PubMed Google Scholar Hoffman, P, Rabe, C, Grant, K, Valverius, P, Hudspith, M, Tabakoff, B 1990 Ethanol and the NMDA receptor. Alcohol 7 229 231 CrossRef PubMed Google Scholar Hu, XJ, Follesa, P, Ticku, MK 1996 Chronic ethanol treatment produces a selective upregulation of the NMDA receptor subunit gene expression in mammalian cultured cortical neurons. Brain Res Mol Brain Res 36 211 218 PubMed Google Scholar Hu, XJ, Ticku, MK 1995 Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons. Brain Res Mol Brain Res 30 347 356 PubMed Google Scholar Huang, RF, Huang, SM, Lin, BS, Wei, JS, Liu, TZ 2001 Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci 68 2799 2811 PubMed Google Scholar Hultberg, B, Berglund, M, Andersson, A, Frank, A 1993 Elevated plasma homocysteine in alcoholics. Alcohol Clin Exp Res 17 687 689 PubMed Google Scholar Kim, WK, Pae, YS 1996 Involvement of N-methyl-d-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci Lett 216 117 120 PubMed Google Scholar Kruman, II, Culmsee, C, Chan, SL, Kruman, Y, Guo, Z, Penix, L, Mattson, MP 2000 Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20 6920 6926 PubMed Google Scholar Lehfeld, H, Erzigkeit, H 1997 The SKT – a short cognitive performance test for assessing deficits of memory and attention. Int Psychogeriatr 9 115 121 PubMed Google Scholar Lehfeld, H, Rudinger, G, Rietz, C, Heinrich, C, Wied, V, Fornazzari, L, Pittas, J, Hindmarch, I, Erzigkeit, H 1997 Evidence of the cross-cultural stability of the factor structure of the SKT short test for assessing deficits of memory and attention. Int Psychogeriatr 9 139 153 PubMed Google Scholar
Lehrl S, Fischer B (1992) c.I.-Test zur Frühdiagnostik von Demenzen. VLESS-Verlag, Ebersberg
Google Scholar Lipton, SA, Kim, WK, Choi, YB, Kumar, S, D’Emilia, DM, Rayudu, PV, Arnelle, DR, Stamler, JS 1997 Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 94 5923 5928 CrossRef PubMed Google Scholar Loscalzo, J 2002 Homocysteine and dementias. N Engl J Med 346 466 468 PubMed Google Scholar Lutz, MT, Clusmann, H, Elger, CE, Schramm, J, Helmstaedter, C 2004 Neuropsychological outcome after selective amygdalohippocampectomy with transsylvian versus transcortical approach: a randomized prospective clinical trial of surgery for temporal lobe epilepsy. Epilepsia 45 809 816 CrossRef PubMed Google Scholar Mann, K, Günther, A, Stetter, F, Ackermann, K 1999 Rapid recovery from cognitive deficits in abstinent alcoholics: a controlled test-retest study. Alcohol 34 567 574 Google Scholar Mattson, MP, Shea, TB 2003 Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26 137 146 CrossRef PubMed Google Scholar Outinen, PA, Sood, SK, Liaw, PC, Sarge, KD, Maeda, N, Hirsh, J, Ribau, J, Podor, TJ, Weitz, JI, Austin, RC 1998 Characterization of the stress-inducing effects of homocysteine. Biochem J 332 213 221 PubMed Google Scholar Prins, ND, Den Heijer, T, Hofman, A, Koudstaal, PJ, Jolles, J, Clarke, R, Breteler, MM 2002 Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study. Neurology 59 1375 1380 PubMed Google Scholar Sachdev, PS, Valenzuela, M, Wang, XL, Looi, JC, Brodaty, H 2002 Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals. Neurology 58 1539 1541 PubMed Google Scholar Seifert, J, Seeland, I, Borsutzky, M, Passie, T, Rollnik, JD, Wiese, B, Emrich, HM, Schneider, U 2003 Effects of acute alcohol withdrawal on memory performance in alcohol-dependent patients: a pilot study. Addict Biol 8 75 80 PubMed Google Scholar Tsai, G 1998 Glutamatergic neurotransmission in alcoholism. J Biomed Sci 5 309 320 PubMed Google Scholar Tsai, GE, Ragan, P, Chang, R, Chen, S, Linnoila, VM, Coyle, JT 1998 Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal. Am J Psychiatry 155 726 732 PubMed Google Scholar Copyright information
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