A figura 11 apresenta as dosagens plasmáticas da vitamina C nos pacientes com DA comparados com o grupo controle. Notamos que houve mudança significativa de acordo com a evolução da doença (p<0,001). Nos estágios leve,moderado e grave observamos valores menores nos pacientes com DA, corroborando com estudos anteriores (FOY et al, 1999; MECOCCI et al, 2002; RINALDI et al, 2003) que mostram em suas análises níveis plasmáticos menores de Vitamina C em pacientes com DA comparados com seus controles. SCHIPPLING et al.,2000 também, mostra em seus estudos que os níveis plasmáticos de ascorbato apresentam-se significativamente diminuídos no grupo pacientes com DA comparado com o grupo controle.Com esses dados podemos concordar com a hipótese, que o excesso de radicais ocorre particularmente em DA, manifestando-se através de um decréscimo de antioxidantes no plasma especialmente vitaminas A, C e E (FOY et al, 1999).Estudos epidemiológicos mostraram que baixos níveis plasmáticos de vitaminas antioxidantes representam um fator de risco para a disfunção cognitiva (LARUE et al, 1997; KALMIJN et al,1997; PALEOLOGOLOS et al, 1998; SCHMIDT et al, 1998), e que os marcadores do estresse oxidativo estão associados com o declínio cognitivo (BERR et al, 2000).
Figura 11 – Níveis plasmáticos de Vitamina C, comparando pacientes DA e grupo controle, teste de Wilcoxon: teste pareado não paramétrico (*p<0,001).
6 CONCLUSÕES
Os resultados presentes neste estudo demonstraram que:
A função cognitiva da maioria dos pacientes encontra-se diminuída nos estágios moderado e grave da doença, o estágio mais grave da doença apresentou menor escore no MEEM, ou seja , um maior declínio cognitivo.
Houve diferença estatística nos parâmetros hematológicos somente para os índices hematimétricos VCM e CHCM, quando comparamos os pacientes DA com os controles.
Houve redução da atividade da enzima δ-ALA-D conforme o avanço dos estágios da DA, comparando-se com o grupo controle.
Não houve diferença significativa referentea atividade da enzima Glutationa Peroxidase (GPx) comparando-se pacientes DA CDR1 ao grupo controle, entretanto, houve diminuição da atividade desta enzima nos pacientes DA CDR2 e CDR3, quando comparados aos seus controles.
Os níveis plasmáticos de vitamina C encontraram-se diminuídos nos três estágios dos pacientes com DA, comparado-se com os controles..
Diante das conclusões acima, podemos observar que quanto maior o declínio cognitivo, maior a redução das atividades enzimáticas δ-ALA-D, GPx e níveis plasmáticos da vitamina C,concordando com estudos precedentes que mostram que essas alterações podem estar ocorrendo paralelamente ao estresse oxidativo.
Há correlação dos parâmetros de Estresse oxidativo em decorrência do declínio cognitivo causado pela DA.
7 REFERÊNCIAS BIBLIOGRÁFICAS
PROTOCOLO CLÍNICO E DIRETRIZES TERAPÊUTICAS - DOENÇA DE
ALZHEIMER.Portaria Nº 1298. Brasil 2013.
ALIEV, G. et al. Cancer and Alzheimer Disease via Oxidative Stress Induced by Nitric Oxide-Dependent Mitochondrial DNA Over proliferation and Deletion. Oxidative medicine and Cellular Longevity,v. 2013, n. 962984, p. 19, 2013.
ALMEIDA, C. C. et al. Redução dos níveis séricos de ácido fólico em pacientes com a doença de Alzheimer.Revista de Psiquiatria Clínicav. 39, n. 3, p. 90-93, 2012.
ALZHEIMER, A. Uber eigenartige Krankheitsfalle des spateren Alters. Zeitschriftfür die gesamteNeurologie und Psychiatrie.v. 4, p. 356-385, 1911.
ALZHEIMER, A.; Übereine eigenartigeErkrankung der Hirnrinde.Allgemeine Zeitschrift fur Psychiatrie und Psychisch-gerichtliche Medizin,v. 64, p. 146-148, 1907.
APRAHAMIAN, I.; MARTINELLI, J. E.; YASSUDA, M. S. Alzheimer's disease: anepidemiology and diagnosis review. Revista Brasileira de Clinica Médica, v. 7, p. 27- 35, 2009.
ARANHA, F. Q. et al. O papel da vitmina C sobre as alterações orgânicas no idoso.Revista de Nutrição.v. 13, p. 89-97, 2000.
AVILA, J. et al. Tau and Neuron Aging. Aging and Disease, v. 4, n. 1, p. 23-28, 2013. ISSN 2152-5250
AZEVEDO, P. G. D. et al. Linguagem e Memória na doença de Alzheimer em fase moderada. Revista CEFAC, p. 87-198, 2009.
BAIERLE, M. et al. Possíveis efeitos do cobre sanguíneo sobre parâmetros hematológicos em idosas. Jornal Brasileirode Patologia e Medicina Laboratorial, v. 46, n. 6, p. 463-70, 2010.
BAINS, J. S.; SHAW, C. A. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Research Reviews,v. 25, n. 3, p. 335-358, 1997. ISSN 0165-0173.
BARNARD, G. et al. Mechanism of porphobilinogen synthase. Possible role of essential thiol groups. Journal of Biological Chemistry, v. 252, n. 24, p. 8965-8974, 1977. ISSN 0021-9258.
BEAL, M. F. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Annals of the New York Academy of Sciences, v. 991, n. 1, p. 120-131, 2003. ISSN 1749-6632.
BECHARA, E. J. et al. A free radical hypothesis of lead poisoning and inborn porphyrias associated with 5-aminolevulinic acid overload. Quimíca Nova, v. 16, p. 385-392, 1993.
BERGER, M. M. Can oxidative damage be treated nutritionally? Clinical nutrition, v. 24, n. 2, p. 172-183, 2005. ISSN 0261-5614.
BERLIN, A.; SCHALLER, K. European standardized method for the determination of delta-aminolevulinic acid dehydratase activity in blood. Z klin Chem klin Biochem, v. 12, n. 8, p. 389-390, 1974. ISSN 0044-2933.
BONNEFONT-ROUSSELOT, D. The role of antioxidant micronutrients in the prevention of diabetic complications. Treatments in endocrinology, v. 3, n. 1, p. 41-52, 2004. ISSN 1175-6349.
BOURDEL‐MARCHASSON, I. et al. Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age and Ageing, v. 30, n. 3, p. 235-241, 2001. ISSN 0002-0729.
BRIGELIUS-FLOHÉ, R. Tissue-specific functions of individual glutathione peroxidases. Free Radical Biology and medicine,v. 27, n. 9, p. 951-965, 1999. ISSN 0891-5849.
BRIGELIUS-FLOHE, R.; TRABER, M. G. Vitamin E: function and metabolism. The FASEB Journal, v. 13, n. 10, p. 1145-1155, 1999. ISSN 0892-6638.
BUTTERFIELD, D. A.; BOYD-KIMBALL, D. The critical role of methionine 35 in Alzheimer's amyloid β-peptide (1–42) -induced oxidative stress and neurotoxicity. Biochimica et Biophysica Acta (BBA) -Proteins and Proteomics,v. 1703, n. 2, p. 149- 156, 2005. ISSN 1570-9639.
CADENAS, E.; DAVIES, K. J. Mitochondrial free radical generation, oxidative stress, and aging. Free Radical Biology and medicine, v. 29, n. 3, p. 222-230, 2000. ISSN 0891-5849.
CADET, J.; DOUKI, T.; RAVANAT, J.-L. Oxidatively generated base damage to cellular DNA. Free Radical Biology and medicine, v. 49, n. 1, p. 9-21, 2010. ISSN 0891-5849.
CAIXETA, L. Evolução do conceito de doença de Alzheimer.Doença de Alzheimer. (ORG.), C. L. Porto Alegre 2012.
CANTIN, A. M. Potential for antioxidant therapy of cystic fibrosis. Current opinion in pulmonary medicine,v. 10, n. 6, p. 531-536, 2004. ISSN 1070-5287.
CAPUTO, F.; VEGLIANTE, R.; GHIBELLI, L. Redox modulation of the DNA damage response. Biochemical pharmacology, v. 84, n. 10, p. 1292-1306, 2012. ISSN 0006- 2952.
CASADO, Á. et al. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochemical research, v. 33, n. 3, p. 450-458, 2008. ISSN 0364-3190.
CHATGILIALOGLU, C. et al. Biomimetic Models of Radical Stress and Related Biomarkers. CHIMIA International Journal for Chemistry, v. 66, n. 6, p. 368-371, 2012. ISSN 0009-4293.
CHAUHAN, V.; CHAUHAN, A. Oxidative stress in Alzheimer's disease. Pathophysiology, v. 13, n. 3, p. 195-208, 2006. ISSN 0928-4680.
CHAVKO, M.; AUKER, C. R.; MCCARRON, R. M. Relationship between protein nitration and oxidation and development of hyperoxic seizures. Nitric oxide,v. 9, n. 1, p. 18-23, 2003. ISSN 1089-8603.
CLARKSON, P. M.; THOMPSON, H. S. Antioxidants: what role do they play in physical activity and health? The American journal of clinical nutrition, v. 72, n. 2, p. 637s-646s, 2000. ISSN 0002-9165.
COHEN, L. Toward an anthropology of senility: anger, weakness, and Alzheimer's in Banaras, India. Medical Anthropology Quarterly, p. 314-334, 1995. ISSN 0745-5194.
DEL VALLE, L. G. Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans. Biomedicine & Aging Pathology, v. 1, n. 1, p. 1-7, 2011. ISSN 2210-5220.
DIERCKX, N. et al. Oxidative stress status in patients with diabetes mellitus: relationship to diet. European journal of clinical nutrition,v. 57, n. 8, p. 999-1008, 2003. ISSN 0954-3007.
DJORDJEVIC, V. δ-Aminolevulinic acid dehydratase activity in erythrocytes of diabetic patients. Archives Of Physiology And Biochemistry, v. 93, n. 4, p. 285-290, 1985. ISSN 1381-3455.
DJORDJEVIĆ, V. et al. Erythrocyte delta-aminolevulinate dehydratase measurements in Balkan endemic nephropathy. Kidney international. Supplement,v. 34, p. S93, 1991. ISSN 0098-6577.
EGGERMONT, E. Recent advances in vitamin E metabolism and deficiency. European journal of pediatrics,v. 165, n. 7, p. 429-434, 2006. ISSN 0340-6199.
ESCOTT-STUMP, S.; MAHAN, K. L. Krause: alimentos, nutrição e dietoterapia. São Paulo: Roca, 2002.
FARACI, F. M. Reactive oxygen species: influence on cerebral vascular tone. Journal of Applied Physiology,v. 100, n. 2, p. 739-743, 2006. ISSN 8750-7587.
FARINA, M. et al. Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves. Brazilian journal of medical and biological research,v. 35, n. 6, p. 623-631, 2002. ISSN 0100-879X.
FARMER, M. E. et al. Blood pressure and cognitive performance the Framingham study. American Journal of Epidemiology, v. 126, n. 6, p. 1103-1114, 1987. ISSN 0002- 9262.
FERNANDEZ-CUARTERO, B. et al. Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus. The international journal of biochemistry & cell biology,v. 31, n. 3, p. 479-488, 1999. ISSN 1357-2725.
FERREIRA, A.; MATSUBARA, L. Radicais livres: conceitos, doenças relacionadas, sistema de defesa e estresse oxidativo. Revista da Associação Médica Brasileira, v. 43, n. 1, p. 61-68, 1997. ISSN 0104-4230.
FERRI, C. P.; AMES, D. Behavioral and psychological symptoms of dementia in developing countries. International Psychogeriatrics,v. 16, n. 04, p. 441-459, 2004. ISSN 1741-203X.
FINKEL, T. Oxidant signals and oxidative stress. Current opinion in cell biology,v. 15, n. 2, p. 247-254, 2003. ISSN 0955-0674.
FONTANELLAS, A. et al. Effects of recombinant human erythropoietin on porphyrin metabolism in uremic patients on hemodialysis. Journal of the American Society of Nephrology,v. 7, n. 5, p. 774-779, 1996. ISSN 1046-6673.
FRIDOVICH, I. Oxygen toxicity: a radical explanation. Journal of Experimental Biology, v. 201, n. 8, p. 1203-1209, 1998. ISSN 0022-0949.
FUSTER, V. et al. Low Priority of Cardiovascular and Chronic Diseases on the Global Health Agenda A Cause for Concern. Circulation,v. 116, n. 17, p. 1966-1970, 2007. ISSN 0009-7322.
GABRIEL, D. et al. Human erythrocyte δ-aminolevulinate dehydratase inhibition by monosaccharides is not mediated by oxidation of enzyme sulfhydryl groups.Cell biology international, v. 29, n. 8, p. 669-674, 2005. ISSN 1065-6995.
GACKOWSKI, D. et al. Oxidative stress and oxidative DNA damage is characteristic for mixed Alzheimer disease/vascular dementia. Journal of the neurological sciences,v. 266, n. 1, p. 57-62, 2008. ISSN 0022-510X.
GAETANI, G. F. et al. Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood, v. 73, n. 1, p. 334- 339, 1989. ISSN 0006-4971.
GASPARRI, S. Estudo das atividades antioxidante e mutagênica/antimutagênica induzidas pelo extrato vegetal da Costus spicatus.2005. Universidade Luterana do Brasil
GELLA, A.; DURANY, N. Oxidative stress in Alzheimer disease. Cell adhesion & migration,v. 3, n. 1, p. 88-93, 2009. ISSN 1933-6918.
GHOSH, D. et al. A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons. The Journal of Neuroscience, v. 32, n. 17, p. 5821-5832, 2012. ISSN 0270-6474.
GIBSON, K. D.; NEUBERGER, A.; SCOTT, J. J. The purification and properties of δ- aminolaevulic acid dehydrase. Biochem J,v. 61, n. 4, p. 618-29, Dec 1955. ISSN 0264- 6021 (Print) 1470-8728 (Electronic).
GLASØ, M. et al. Reduced concentrations of several vitamins in normal weight patients with late-onset dementia of the Alzheimer type without vascular disease. The journal of nutrition, health & aging,v. 8, n. 5, p. 407-413, 2003. ISSN 1279-7707.
GOLDE, T. E. The Pathogenesis of Alzheimer’s disease and role of Aβ42. CNS Spectrums, v. 12, p. 4-6, 2007.
GONÇALVES, T. L. et al. Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women. Clinical biochemistry, v. 38, n. 12, p. 1071-1075, 2005. ISSN 0009-9120.
GREEN, K.; BRAND, M. D.; MURPHY, M. P. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes,v. 53, n. suppl 1, p. S110-S118, 2004. ISSN 0012-1797.
GRUNDMAN, M. Vitamin E and Alzheimer disease: the basis for additional clinical trials. The American journal of clinical nutrition,v. 71, n. 2, p. 630s-636s, 2000. ISSN 0002-9165.
GRÜNING, N.-M.; LEHRACH, H.; RALSER, M. Regulatory crosstalk of the metabolic network. Trends in biochemical sciences,v. 35, n. 4, p. 220-227, 2010. ISSN 0968-0004.
HAASS, C. et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature,v. 359, n. 6393, p. 322-325, 1992. ISSN 0028-0836.
HAASS, C.; SELKOE, D. J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nature reviews Molecular cell biology, v. 8, n. 2, p. 101-112, 2007. ISSN 1471-0072.
HALLIWELL, B. Reactive oxygen species and the central nervous system. In: (Ed.). Free radicals in the brain: Springer, 1992. p.21-40. ISBN 3642776116.
HALLIWELL, B. Role of free radicals in the neurodegenerative diseases. Drugs & aging,v. 18, n. 9, p. 685-716, 2001. ISSN 1170-229X.
HALLIWELL, B. Proteasomal dysfunction: a common feature of neurodegenerative diseases? Implications for the environmental origins of neurodegeneration. Antioxidants & redox signaling, v. 8, n. 11-12, p. 2007-2019, 2006. ISSN 1523-0864.
HALLIWELL, B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant physiology, v. 141, n. 2, p. 312-322, 2006. ISSN 0032-0889.
HALLIWELL, B.; GUTTERRIDGE, J. M. Free radicals and antioxidants–quo vadis? Trends in pharmacological sciences, v. 32, n. 3, p. 125-130, 2011. ISSN 0165-6147.
HALLIWELL, B.; GUTTERIDGE, J. Role of free radical and catalytic metal ions in human disease: an overview. 1990.
HALLIWELL, B.; GUTTERIDGE, J. M. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Archives of biochemistry and biophysics, v. 246, n. 2, p. 501-514, 1986. ISSN 0003-9861.
HALLIWELL, B.; GUTTERRIDGE, J. M. Free radicals in biology and medicine. Oxford University press Oxford, 1999.
HALLIWELL, B.; GUTTERRIDGE, J. M. Free Radical in Biology and medicine. Oxford: Oxford University Press, 2007.
HALLIWELL, B.; WHITEMAN, M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? British journal of pharmacology, v. 142, n. 2, p. 231-255, 2004. ISSN 1476-5381.
HARDY, J.; SELKOE, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, v. 297, n. 5580, p. 353-356, 2002. ISSN 0036-8075.
HEBERT, L. et al. Blood pressure and late-life cognitive function change A biracial longitudinal population study. Neurology, v. 62, n. 11, p. 2021-2024, 2004. ISSN 0028- 3878.
HERNÁNDEZ, F. et al. GSK3: a possible link between beta amyloid peptide and tau protein. Experimental neurology, v. 223, n. 2, p. 322-325, 2010. ISSN 0014-4886.
HERZ, J.; BEFFERT, U. Apolipoprotein E receptors: linking brain development and Alzheimer's disease. Nature Reviews Neuroscience, v. 1, n. 1, p. 51-58, 2000. ISSN 1471-003X.
HOOPER, C.; KILLICK, R.; LOVESTONE, S. The GSK3 hypothesis of Alzheimer’s disease. Journal of neurochemistry,v. 104, n. 6, p. 1433-1439, 2008. ISSN 1471-4159.
IBGE, I. Sinopse do censo demográfico 2010. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística, p. 261, 2011.
INTERNATIONAL, A. S. D. RELATÓRIO SOBRE A DOENÇA DE ALZHEIMER NO MUNDO DE 2009.INTERNATIONAL, A. S. D. Londres: Alzheimer’s disease International 2010.
ITTNER, L. M.; GÖTZ, J. Amyloid-β and tau—a toxic pas de deux in Alzheimer's disease. Nature Reviews Neuroscience,v. 12, n. 2, p. 67-72, 2011. ISSN 1471-003X.
IVAN, C. S. et al. Dementia after stroke the Framingham study. Stroke,v. 35, n. 6, p. 1264-1268, 2004. ISSN 0039-2499.
JACQUES‐SILVA, M. C. et al. Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice. Pharmacology & toxicology,v. 88, n. 3, p. 119-125, 2001. ISSN 1600-0773.
JELLINGER, K. General Aspects of neurodegeneration. In: (Ed.).Advances in Research on Neurodegeneration: Springer, 2003. P.101-144. ISBN 3211839070.
JONES, D. P. Redefining oxidative stress. Antioxidants & redox signaling,v. 8, n. 9-10, p. 1865-1879, 2006. ISSN 1523-0864.
JÚNIOR, L. R. et al. Sistema antioxidante envolvendo o ciclo metabólico da glutationa associado a métodos eletroanalíticos na avaliação do estresse oxidativo. Quimíca. Nova, v. 24, n. 1, p. 112-119, 2001.
KALIORA, A.; DEDOUSSIS, G.; SCHMIDT, H. Dietary antioxidants in preventing atherogenesis. Atherosclerosis,v. 187, n. 1, p. 1-17, 2006. ISSN 0021-9150.
KHARRAZI, H. et al. Association between enzymatic and non-enzymatic antioxidant defense mechanism with apolipoprotein E genotypes in Alzheimer disease.Clinical biochemistry, v. 41, n. 12, p. 932-936, 2008. ISSN 0009-9120.
KONTUSH, A.; SCHEKATOLINA, S. Vitamin E in Neurodegenerative Disorders: Alzheimer's disease. Annals of the New York Academy of Sciences,v. 1031, n. 1, p. 249- 262, 2004. ISSN 1749-6632.
KOURY, J. C.; DONANGELO, C. M. Zinco, estresse oxidativo e atividade física. Revista de nutrição,v. 16, n. 4, p. 433-441, 2003.
KRYSTON, T. B. et al. Role of oxidative stress and DNA damage in human carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v. 711, n. 1, p. 193-201, 2011. ISSN 0027-5107.
LAFERLA, F. M.; GREEN, K. N.; ODDO, S. Intracellular amyloid-β in Alzheimer's disease. Nature Reviews Neuroscience,v. 8, n. 7, p. 499-509, 2007. ISSN 1471-003X.
LAURIN, D. et al. Midlife dietary intake of antioxidants and risk of late-life incident dementia the Honolulu-Asia Aging Study. American journal of epidemiology,v. 159, n. 10, p. 959-967, 2004. ISSN 0002-9262.
LEE, I.-M. et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. Jama, v. 294, n. 1, p. 56-65, 2005. ISSN 0098-7484.
LIN, M. T.; BEAL, M. F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature,v. 443, n. 7113, p. 787-795, 2006. ISSN 0028-0836.
LIU, H. et al. Redox-dependent transcriptional regulation. Circulation Research,v. 97, n. 10, p. 967-974, 2005. ISSN 0009-7330.
LUCHSINGER, J. A. et al. Antioxidant vitamin intake and risk of Alzheimer disease. Archives of neurology,v. 60, n. 2, p. 203-208, 2003. ISSN 0003-9942.
MAHMOODI, M. R.; KIMIAGAR, M.; MEHRABI, Y. The effects of omega-3 plus vitamin E and zinc plus vitamin C supplementation on cardiovascular risk markers in postmenopausal women with type 2 diabetes. Therapeutic advances in endocrinology and metabolism, v. 5, n. 4, p. 67-76, 2014. ISSN 2042-0188.
MANELA-AZULAY, M. et al. Vitamin C. Anais brasileiros de dermatologia, v. 78, n. 3, p. 265-272, 2003. ISSN 0365-0596.
MANTHA, A. K. et al. Neuroprotective role of neurokinin B (NKB) on β-amyloid (25– 35) induced toxicity in aging rat brain synaptosomes: involvement in oxidative stress and excitotoxicity. Biogerontology,v. 7, n. 1, p. 1-17, 2006. ISSN 1389-5729.
MARIANI, E. et al. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. Journal of Chromatography B,v. 827, n. 1, p. 65-75, 2005. ISSN 1570-0232.
MARKESBERY, W. R. The role of oxidative stress in Alzheimer disease. Archives of Neurology, v. 56, n. 12, p. 1449-1452, 1999. ISSN 0003-9942.
MARKESBERY, W. R.; LOVELL, M. A. DNA oxidation in Alzheimer's disease. Antioxidants & redox signaling,v. 8, n. 11-12, p. 2039-2045, 2006. ISSN 1523-0864.
MARTÍN-ARAGÓN, S. et al. Metalloproteinase’s activity and oxidative stress in mild cognitive impairment and Alzheimer’s disease. Neurochemical research, v. 34, n. 2, p. 373-378, 2009. ISSN 0364-3190.
MARTı́NEZ, B.; RINCÓN, F.; IBÁÑEZ, M. Effects of ascorbic acid and ferrous sulfate on trace element extractability by dialyzation of weaning foods. Food chemistry,v. 86, n. 3, p. 369-376, 2004. ISSN 0308-8146.
MATTSON, M. P. Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders. Antioxidants & redox signaling, v. 8, n. 11-12, p. 1997-2006, 2006. ISSN 1523-0864.
MATTSON, M. P.; CHAN, S. L. Neuronal and glial calcium signaling in Alzheimer’s disease. Cell calcium,v. 34, n. four, p. 385-397, 2003. ISSN 0143-4160.
MAYEUX, R.; STERN, Y. Epidemiology of Alzheimer disease. Cold Spring Harbor perspectives in medicine, v. 2, n. 8, p. a006239, 2012. ISSN 2157-1422.
MCGRATH, L. et al. Increased oxidative stress in Alzheimer's disease as assessed with 4‐hydroxynonenal but not malondialdehyde. Qjm,v. 94, n. 9, p. 485-490, 2001. ISSN 1460-2725.
MIGLIORE, L.; COPPEDÈ, F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, v. 674, n. 1, p. 73-84, 2009. ISSN 1383-5718.
MONTEIRO, H. P. et al. Free radical generation during δ-aminolevulinic acid autoxidation: induction by hemoglobin and connections with porphyrinpathies.Archives of biochemistry and biophysics, v. 271, n. 1, p. 206-216, 1989. ISSN 0003-9861.
MOREIRA, P. I. et al. Nucleic acid oxidation in Alzheimer disease. Free Radical Biology and medicine,v. 44, n. 8, p. 1493-1505, 2008. ISSN 0891-5849.
MORRIS, M. C. et al. Association between blood pressure and cognitive function in a biracial community population of older persons. Neuroepidemiology, v. 21, n. 3, p. 123- 130, 2002. ISSN 1423-0208.
NISHIDA, Y. et al. Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse. Biochemical and biophysical research communications,v. 350, n. 3, p. 530-536, 2006. ISSN 0006-291X.
NOGUEIRA, C. et al. Organochalcogens effects on δ-aminolevulinate dehydratase activity from human erythrocytic cells in vitro. Toxicology,v. 191, n. 2, p. 169-178, 2003. ISSN 0300-483X.
NOGUEIRA, C. et al. 2, 3-Dimercaptopropane-1-sulfonic acid and meso-2, 3- dimercaptosuccinic acid increase mercury-and cadmium-induced inhibition of δ- aminolevulinate dehydratase. Toxicology,v. 184, n. 2, p. 85-95, 2003. ISSN 0300-483X. OFFICE, N. A. Improving services and support for people with dementia: National Audit Office London 2007.
OLIVEIRA, J. D. C.; ALBUQUERQUE, F.; LINS, I. B. Projeção da população do Brasil por sexo e idade para o período 1980-2050–revisão 2004. Rio de Janeiro, IBGE, 2004.
PAGLIA, D. E.; VALENTINE, W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.The Journal of laboratory and clinical medicine, v. 70, n. 1, p. 158-169, 1967. ISSN 0022-2143.
PANIZ, C. et al. The influence of the serum vitamin C levels on oxidative stress biomarkers in elderly women. Clinical biochemistry,v. 40, n. 18, p. 1367-1372, 2007. ISSN 0009-9120.
PATEL, V.; PRINCE, M. Ageing and mental health in a developing country: who cares? Qualitative studies from Goa, India. Psychological medicine,v. 31, n. 01, p. 29- 38, 2001. ISSN 1469-8978.
PENCKOFER, S.; SCHWERTZ, D.; FLORCZAK, K. Oxidative stress and cardiovascular disease in type 2 diabetes: the role of antioxidants and pro-oxidants. Journal of Cardiovascular Nursing,v. 16, n. 2, p. 68-85, 2002. ISSN 0889-4655.
POCERNICH, C. B.; BUTTERFIELD, D. A. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, v. 1822, n. 5, p. 625-630, 2012. ISSN 0925-4439.
POLIDORI, M. C. et al. Plasma antioxidant status, immunoglobulin g oxidation and lipid peroxidation in demented patients: relevance to Alzheimer disease and vascular dementia. Dementia and geriatric cognitive disorders,v. 18, n. 3-4, p. 265-270, 2004. ISSN 1421-9824.
POLIDORI, M. C.; MECOCCI, P. Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease. Journal of Alzheimer's disease: JAD, v. 4, n. 6, p. 517-522, 2002. ISSN 1387-2877.
RAUK, A. The chemistry of Alzheimer’s disease. Chemical Society Reviews,v. 38, n. 9, p. 2698-2715, 2009.
REISBERG, B. et al. Memantine in moderate-to-severe Alzheimer's disease. New England Journal of medicine,v. 348, n. 14, p. 1333-1341, 2003. ISSN 0028-4793.
REITER, E.; JIANG, Q.; CHRISTEN, S. Anti-inflammatory properties of α-and γ- tocopherol. Molecular aspects of medicine,v. 28, n. 5, p. 668-691, 2007. ISSN 0098- 2997.
REITZ, C.; BRAYNE, C.; MAYEUX, R. Epidemiology of Alzheimer disease. Nature Reviews Neurology,v. 7, n. 3, p. 137-152, 2011. ISSN 1759-4758.
REN, J. et al. Study of the catalytic electro-oxidation of ascorbic acid on an electrode modified by macrocyclic compounds of Fe (III), Mn (III), Ni (II), and Co (II) with TBP. Journal of Electroanalytical Chemistry,v. 504, n. 1, p. 59-63, 2001. ISSN 1572-6657.
RESENDE, R. et al. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radical Biology and medicine,v. 44, n. 12, p. 2051-2057, 2008. ISSN 0891-5849.
RICCIARELLI, R. et al. Vitamin E and neurodegenerative diseases. Molecular aspects of medicine,v. 28, n. 5, p. 591-606, 2007. ISSN 0098-2997.
RICCIARELLI, R.; ZINGG, J. M.; AZZI, A. Vitamin E 80th anniversary: a double life, not only fighting radicals. IUBMB life,v. 52, n. 1, p. 71-76, 2001. ISSN 1521-6551.
ROLO, A. P.; TEODORO, J. S.; PALMEIRA, C. M. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radical Biology and medicine,v. 52, n. 1, p. 59-69, 2012. ISSN 0891-5849.
SANTOS, F. W. et al. Cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice. Toxicology letters,v. 152, n. 3, p. 255-263, 2004. ISSN 0378-4274.
SASSA, S. Delta-aminolevulinic acid dehydratase assay. Enzyme,v. 28, n. 2-3, p. 133- 145, 1981. ISSN 0013-9432.
SCARMEAS, N. et al. Physical Activity, Diet, and Risk of Alzheimer Disease.JAMA V.302, n.6,p. 627–637, 2009. doi:10.1001/jama.2009.1144.
SCHAEFFER, E. L.; FIGUEIRO, M.; GATTAZ, W. F. Insights into Alzheimer disease pathogenesis from studies in transgenic animal models. Clinics, v. 66, p. 45-54, 2011. ISSN 1807-5932.
SCHEIBMEIR, H. D. et al. A review of free radicals and antioxidants for critical care nurses. Intensive and Critical Care Nursing, v. 21, n. 1, p. 24-28, 2005. ISSN 0964- 3397.
SCHNEIDER, C. D.; OLIVEIRA, A. D. Radicais livres de oxigênio e exercício: mecanismos de formação e adaptação ao treinamento físico. Rev Bras Med Esporte,v. 10, n. 4, p. 308-13, and 2004.
SCHULZ, J. B. et al. Glutathione, oxidative stress and neurodegeneration. European Journal of Biochemistry,v. 267, n. 16, p. 4904-4911, 2000. ISSN 1432-1033.
SELKOE, D. J.; SCHENK, D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annual review of pharmacology and toxicology,v. 43, n. 1, p. 545-584, 2003. ISSN 0362-1642.
SEN, C. K.; KHANNA, S.; ROY, S. Tocotrienols: vitamin E beyond tocopherols. Life sciences, v. 78, n. 18, p. 2088-2098, 2006. ISSN 0024-3205.
SHAJI, K. S. et al. Caregivers of people with Alzheimer's disease: a qualitative study from the Indian 10/66 Dementia Research Network. International journal of geriatric psychiatry, v. 18, n. 1, p. 1-6, 2003. ISSN 1099-1166.
SHAMI, N.; MOREIRA, E. A. M. Licopeno como agente antioxidante. Rev Nutr,v. 17, n. 2, p. 227-36, 2004.
SINGH-MANOUX, A.; MARMOT, M. High blood pressure was associated with cognitive function in middle-age in the Whitehall II study. Journal of clinical epidemiology,v. 58, n. 12, p. 1308-1315, 2005. ISSN 0895-4356.
SOUZA, J. B. et al. Delta-aminolevulinate dehydratase (δ-ALA-D) activity in diabetes and hypothyroidism. Clinical biochemistry,v. 40, n. 5, p. 321-325, 2007. ISSN 0009- 9120.
STINE, W. B. et al. In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis. Journal of Biological Chemistry,v. 278, n. 13, p. 11612-11622, 2003. ISSN 0021-9258.
STOCKER, R.; KEANEY, J. F. Role of oxidative modifications in atherosclerosis. Physiological reviews,v. 84, n. 4, p. 1381-1478, 2004. ISSN 0031-9333.
SUNDAR, I. K. et al. Oxidative stress, thiol redox signaling methods in epigenetics. Methods in enzymology,v. 474, p. 213-244, 2010. ISSN 0076-6879.
THEMELIS, D. G.; TZANAVARAS, P. D.; KIKA, F. S. On-line dilution flow injection manifold for the selective spectrophotometric determination of ascorbic acid based on the Fe (II) -2, 2′-dipyridyl-2-pyridylhydrazone complex formation. Talanta,v. 55, n. 1, p. 127-134, 2001. ISSN 0039-9140.
VALENTINI, J. et al. Human erythrocyte δ-aminolevulinate dehydratase activity and oxidative stress in hemodialysis patients. Clinical biochemistry,v. 40, n. 9, p. 591-594,