The worldwide challenge of the dementias: A role for B vitamins and homocysteine?

Food and Nutrition Bulletin

Volumn 29, Issue 2 SUPPL., 2008, Pages

  Smith, A David ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Aged; Alzheimer's disease; Burden of disease; Dementia; Disease prevention; Epidemiology; Folic acid; Homocysteine; Humans; Risk factors; Vitamin B12; Vitamin B6

Indexed keywords

AGING POPULATION; CONFERENCE PROCEEDING; DISEASE PREVALENCE; EPIDEMIOLOGY; MENTAL HEALTH; RISK FACTOR; VITAMIN DEFICIENCY;

EID: 48249091668     PISSN: 03795721     EISSN: None     Source Type: Journal    
DOI: 10.1177/15648265080292s119     Document Type: Conference Paper

References (305)

1. Menken M, Munsat TL, Toole JF. The global burden of disease study: Implications for neurology. Arch Neurol 2000;57:418-20.
2. WHO. Active Ageing. A Policy Framework 2002. Available at: http:// whqlibdoc.who.int/hq/2002/WHO_NMH_NPH_02.8.pdf. Accessed 18 March 2008.
3. Fratiglioni L, DeRonchi D, Aguero-Torres H. Worldwide prevalence and incidence of dementia. Drug Aging 1999;15:365-75.
4. Erkinjuntti T, Ostbye T, Steenhuis R, Hachinski V. The effect of different diagnostic criteria on the prevalence of dementia. N Engl J Med 1997;337:1667-74.
5. Prince M. Methodological issues for population-based research into dementia in developing countries. A position paper from the 10/66 Dementia Research Group. Int J Geriatr Psychiatry 2000;15:21-30.
6. Prince M, Acosta D, Chiu H, Scazufca M, Varghese M. Dementia diagnosis in developing countries: A cross-cultural validation study. Lancet 2003;361:909-17.
7. WHO. Point prevalence for selected causes by sex, age and WHO subregion 2002. Available at: http://www.who.int/healthinfo/statistics/ gbdwhoregionprevalence2002.xls. Accessed 5 May 2008.
8. Wimo A, Winblad B, Aguero-Torres H, von Strauss E. The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 2003;17:63-7.
9. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: Prevalence estimates using the 2000 census. Arch Neurol 2003; 60:1119-22.
10. Paulino Ramirez Diaz S, Gil Gregorio P, Manuel Ribera Casado J, Reynish E, Jean Ousset P, Vellas B, Salmon E. The need for a consensus in the use of assessment tools for Alzheimer's disease: The Feasibility Study (assessment tools for dementia in Alzheimer Centres across Europe), a European Alzheimer's Disease Consortium's (EADC) survey. Int J Geriatr Psychiatry 2005;20:744-8.
11. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M. Global prevalence of dementia: A Delphi consensus study. Lancet 2005;366:2112-7.
12. Wimo A, Jonsson B, Karlsson G, Winblad B, eds. Health economics of dementia. Chichester, UK: Wiley, 1998.
13. Lowin A, Knapp M, McCrone P. Alzheimer's disease in the UK: Comparative evidence on cost of illness and volume of health services research funding. Int J Geriatr Psychiatry 2001;16:1143-8.
14. Wimo A, Jonsson L, Winblad B. An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dement Geriatr Cogn Disord 2006;21:175-81.
15. Rice DP, Fillit HM, Max W, Knopman DS, Lloyd JR, Duttagupta S. Prevalence, costs, and treatment of Alzheimer's disease and related dementia: A managed care perspective. Am J Manag Care 2001;7:809-18.
16. Koppel R. Alzheimer's disease: The costs to U.S. businesses in 2002. Available at: http://www.alz.org/national/documents/ report_alzcosttobusiness.pdf. Accessed 20 March 2008.
17. Lewin Group. Saving lives. Saving money: Dividends for Americans investing in Alzheimer research 2004. Available at: http://www.alz.org/ national/documents/report_savinglivessavingmoney.pdf. Accessed 18 March 2008.
18. Khachaturian ZS, Khachaturian AS. Public health premise for national research priorities: Mortality versus disability. Alz Dem J Alz Assoc 2005;1:2-4.
19. Sloane PD, Zimmerman S, Suchindran C, Reed P, Wang L, Boustani M, Sudha S. The public health impact of Alzheimer's disease, 2000-2050: Potential implication of treatment advances. Annu Rev Public Health 2002; 23:213-31.
20. Breitner JC. The end of Alzheimer's disease? Int J Geriatr Psychiatry 1999;14:577-86.
21. Haan MN, Wallace R. Can dementia be prevented? Brain aging in a population-based context. Annu Rev Public Health 2004;25:1-24.
22. Rowe JW, Kahn RL. Human aging: Usual and successful. Science 1987;237:143-9.
23. O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST. Vascular cognitive impairment. Lancet Neurol 2003;2:89-98.
24. Hachinski V. Preventable senility - a call for action against the vascular dementias. Lancet 1992;340:645-8.
25. Bowler JV, Hachinski V, eds. Vascular cognitive impairment: Preventable dementia. Oxford, UK: Oxford University Press, 2003.
26. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. JAMA 1997;278:1349-56.
27. Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, van Duijn CM, Kehoe PG. Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease. Am J Epidemiol 2005;162:305-17.
28. Breteler MM. Vascular risk factors for Alzheimer's disease: An epidemiologic perspective. Neurobiol Aging 2000;21:153-60.
29. Launer LJ. Demonstrating the case that Alzheimer's disease is a vascular disease: Epidemiologic evidence. Ageing Res Rev 2002;1:61-77.
30. de la Torre JC. Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 2004;3:184-90.
31. Launer LJ. The epidemiologic study of dementia: A life-long quest? Neurobiol Aging 2005;26:335-40.
32. Lawlor DA, Smith GD, Leon DA, Sterne JA, Ebrahim S. Secular trends in mortality by stroke subtype in the 20th century: A retrospective analysis. Lancet 2002;360:1818-23.
33. Rothwell PM, Coull AJ, Giles MF, Howard SC, Silver LE, Bull LM, Gutnikov SA, Edwards P, Mant D, Sackley CM, Farmer A, Sandercock PA, Dennis MS, Warlow CP, Bamford JM, Anslow P. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004;363:1925-33.
34. Strong K, Mathers C, Leeder S, Beaglehole R. Preventing chronic diseases: How many lives can we save? Lancet 2005;366:1578-82.
35. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartin C, Scott JM. Facts and recommendations about total homocysteine determinations: An expert opinion. Clin Chem 2004;50:3-32.
36. Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693-8.
37. 12 with normal blood and marrow. Q J Med 1965;34:303-17.
38. Strachan RW, Henderson JG. Dementia and folate deficiency. Q J Med 1967;36:189-204.
39. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8.
40. 12 deficiency and dementia. Int J Geriatr Psychiatry 1996;11:851-8.
41. Rosenberg IH, Miller JW. Nutritional factors in physical and cognitive functions of elderly people. Am J Clin Nutr 1992;55:1237S-43S.
42. McCaddon A, Kelly CL. Alzheimer's disease: A 'cobalaminergic' hypothesis. Med Hypotheses 1992;37:161-5.
43. Regland B, Gottfries CG. Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease? Med Hypoth 1992;38:11-9.
44. 12 deficiency in primary degenerative dementia. Dementia 1990;1:272-7.
45. Bell IR, Edman JS, Selhub J, Morrow FD, Marby DW, Kayne HL, Cole JO. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand 1992;86:386-90.
46. Nilsson K, Gustafson L, Faldt R, Andersson A, Hultberg B. Plasma homocysteine in relation to serum cobalamin and blood folate in a psychogeriatric population. Eur J Clin Invest 1994;24:600-6.
47. Nilsson K, Gustafson L, Faldt R, Andersson A, Brattstrom L, Lindgren A, Israelsson B, Hultberg B. Hyperhomocysteinaemia - A common finding in a psychogeriatric population. Eur J Clin Invest 1996;26:853-9.
48. 12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J Gerontol Ser A Biol Sci Med 1997;52:M76-9.
49. McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 1998;13:235-9.
50. 12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449-55.
51. 6, and vascular disease in Alzheimer's disease patients. Neurology 2002;58:1471-5.
52. Nilsson K, Gustafson L, Hultberg B. Relation between plasma homocysteine and Alzheimer's disease. Dement Geriatr Cogn Disord 2002;14:7-12.
53. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr 2000;71:614S-20S.
54. Calvaresi E, Bryan J. B vitamins, cognition, and aging: A review. J Gerontol B Psychol Sci Soc Sci 2001;56:327-39.
55. Reutens S, Sachdev P. Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry 2002;17:859-64.
56. Smith AD. Homocysteine, B vitamins, and cognitive deficit in the elderly. Am J Clin Nutr 2002;75:785-6.
57. Morris MS. Homocysteine and Alzheimer's disease. Lancet Neurol 2003;2:425-8.
58. Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ 2004;171:897-904.
59. Ellinson M, Thomas J, Patterson A. A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. J Hum Nutr Diet 2004;17:371-83.
60. Troen A, Rosenberg I. Homocysteine and cognitive function. Semin Vasc Med 2005;5:209-14.
61. Hogervorst E, Barnetson L, Jobst KA, Nagy Z, Combrinck M, Smith AD. Diagnosing dementia: Interrater reliability assessment and accuracy of the NINCDS/ADRDA criteria versus CERAD histopathological criteria for Alzheimer's disease. Dement Geriatr Cogn Disord 2000;11:107-13.
62. Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, Small GW, Miller B, Stevens JC. Practice parameter: Diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1143-53.
63. Gold G, Bouras C, Canuto A, Bergallo MF, Herrmann FR, Hof PR, Mayor PA, Michel JP, Giannakopoulos P. Clinicopathological validation study of four sets of clinical criteria for vascular dementia. Am J Psychiatry 2002;159:82-7.
64. van Straaten EC, Scheltens P, Knol DL, van Buchem MA, van Dijk EJ, Hofman PA, Karas G, Kjartansson O, de Leeuw FE, Prins ND, Schmidt R, Visser MC, Weinstein HC, Barkhof F. Operational definitions for the NINDS-AIREN criteria for vascular dementia: An interobserver study. Stroke 2003;34:1907-12.
65. Hogervorst E, Bandelow S, Combrinck M, Irani SR, Smith AD. The validity and reliability of 6 sets of clinical criteria to classify Alzheimer's disease and vascular dementia in cases confirmed post-mortem: Added value of a decision tree approach. Dement Geriatr Cogn Disord 2003;16:170-80.
66. Budge M, Johnston C, Hogervorst E, de Jager C, Milwain E, Iversen SD, Barnetson L, King E, Smith AD. Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann NY Acad Sci 2000;903:407-10.
67. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002;75:908-13.
68. Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1152-61.
69. Schafer JH, Glass TA, Bolla KI, Mintz M, Jedlicka AE, Schwartz BS. Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc 2005;53:381-8.
70. Elias MF, Sullivan LM, D'Agostino RB, Elias PK, Jacques PF, Selhub J, Seshadri S, Au R, Beiser A, Wolf PA. Homocysteine and cognitive performance in the Framingham offspring study: Age is important. Am J Epidemiol 2005;162:644-53.
71. Luchsinger JA, Tang MX, Shea S, Miller J, Green R, Mayeux R. Plasma homocysteine levels and risk of Alzheimer disease. Neurology 2004;62:1972-6.
72. 12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med 2005;118:161-7.
73. Robbins MA, Elias MF, Budge MM, Brennan SL, Elias PK. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study. Clin Chem Lab Med 2005;43:1101-6.
74. McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C. Homocysteine and cognitive decline in healthy elderly. Dement Geriatr Cogn Disord 2001;12:309-13.
75. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476-83.
76. Teunissen CE, Blom AH, Van Boxtel MP, Bosma H, De Bruijn C, Jolles J, Wauters BA, Steinbusch HW, De Vente J. Homocysteine: A marker for cognitive performance? A longitudinal follow-up study. J Nutr Health Aging 2003;7:153-9.
77. Garcia A, Haron Y, Pulman K, Hua L, Freedman M. Increases in homocysteine are related to worsening of Stroop scores in healthy elderly persons: A prospective follow-up study. J Gerontol A Biol Sci Med Sci 2004;59:1323-7.
78. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, Licastro F. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 2005;82:636-43.
79. Nurk E, Refsum H, Tell GS, Engedal K, Vollset SE, Ueland PM, Nygaard HA, Smith AD. Plasma total homocysteine and memory in the elderly: The Hordaland Homocysteine study. Ann Neurol 2005;58:847-57.
80. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983;249:2917-21.
81. Fioravanti M, Ferrario E, Massaia M, Cappa G, Rivolta G, Grossi E, Buckley AE. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch Gerontol Geriatr 1997;26:1-13.
82. McNulty H, Dowey LR, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C → T polymorphism. Circulation 2006; 113:74-80.
83. La Rue A, Koehler KM, Wayne SJ, Chiulli SJ, Haaland KY, Garry PJ. Nutritional status and cognitive functioning in a normally aging sample: A 6-year reassessment. Am J Clin Nutr 1997;65:20-9.
84. Corrada M, Kawas CH, Hallfrisch J, Muller D, Brookmeyer R. Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging. Alzheimers Dement 2005;1:11-8.
85. Glaso M, Nordbo G, Diep L, Bohmer T. Reduced concentrations of several vitamins in normal weight patients with late-onset dementia of the Alzheimer type without vascular disease. J Nutr Health Aging 2004;8:407-13.
86. Polyak Z, Stern F, Berner YN, Sela BA, Gomori JM, Isayev M, Doolman R, Levy S, Dror Y. Hyperhomocysteinemia and vitamin score: Correlations with silent brain ischemic lesions and brain atrophy. Dement Geriatr Cogn Disord 2003;16:39-45.
87. 12 and folate in relation to the development of Alzheimer's disease. Neurology 2001;56:1188-94.
88. Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol 1990;34:99-107.
89. Carmel R. Cobalamin deficiency. In: Carmel R, Jacobsen DW, eds. Homocysteine in health and disease. Cambridge, UK: Cambridge University Press, 2001:289-305.
90. 12 (cobalamin) status in vegetarians. Am J Clin Nutr 1994;59:1213S-22S.
91. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med 1994;96:239-46.
92. Hvas AM, Nexo E. Holotranscobalamin - a first choice assay for diagnosing early vitamin B deficiency? J Intern Med 2005;257:289-98.
93. 12 status in confirmed Alzheimer's disease as revealed by serum holotranscobalamin. J Neurol Neurosurg Psychiatry 2003;74:959-61.
94. 12, holotranscobalamin and risk of cognitive impairment in older people. Haematologica Reports 2005;1(3):3 (abstract C002).
95. 12 /folate status of elderly Europeans. J Nutr Health Aging 2002;6:43-50.
96. Dufouil C, Alperovitch A, Ducros V, Tzourio C. Homocysteine, white matter hyperintensities, and cognition in healthy elderly people. Ann Neurol 2003;53:214-21.
97. 12, and folic acid and the risk of cognitive decline in old age: The Leiden 85-Plus study. Am J Clin Nutr 2005;82:866-71.
98. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A 3rd. High homocysteine and low B vitamins predict cognitive decline in aging men: The Veterans Affairs Normative Aging Study. Am J Clin Nutr 2005;82:627-35.
99. Gunter EW, Bowman BA, Caudill SP, Twite DB, Adams MJ, Sampson EJ. Results of an international round robin for serum and whole-blood folate. Clin Chem 1996;42:1689-94.
100. 12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5.
101. 12 status in relation to anemia, macrocytosis, and cognitive impairment among older Americans in the age of folic acid fortification. Am J Clin Nutr 2007;85:193-200.
102. Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, Potter JD, Ulrich CM. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006;136:189-94.
103. Ramos MI, Allen LH, Mungas DM, Jagust WJ, Haan MN, Green R, Miller JW. Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005;82:1346-52.
104. Greenland S. Basic methods for sensitivity analysis of biases. Int J Epidemiol 1996;25:1107-16.
105. Lawlor DA, Davey Smith G, Kundu D, Bruckdorfer KR, Ebrahim S. Those confounded vitamins: What can we learn from the differences between observational versus randomised trial evidence? Lancet 2004;363:1724-7.
106. Rydlewicz A, Simpson JA, Taylor RJ, Bond CM, Golden MH. The effect of folic acid supplementation on plasma homocysteine in an elderly population. QJM 2002;95:27-35.
107. Homocysteine LTC. Dose-dependent effects of folic acid on blood concentrations of homocysteine: A meta-analysis of the randomized trials. Am J Clin Nutr 2005;82:806-12.
108. Ohm TG, Muller H, Braak H, Bohl J. Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes. Neuroscience 1995;64:209-17.
109. Elias MF, Beiser A, Wolf PA, Au R, White RF, D'Agostino RB. The preclinical phase of Alzheimer disease: A 22-year prospective study of the Framingham Cohort. Arch Neurol 2000;57:808-13.
110. Smith AD. Imaging the progression of Alzheimer pathology through the brain. Proc Natl Acad Sci USA 2002;99:4135-7.
111. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci USA 2004;101:284-9.
112. Whalley LJ, Dick FD, McNeill G. A life-course approach to the aetiology of late-onset dementias. Lancet Neurol 2006;5:87-96.
113. Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci 2001;22:195-201
114. Smith GD, Ebrahim S. 'Mendelian randomization': Can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003;32:1-22.
115. Casas JP, Bautista LE, Smeeth U, Sharma P, Hingorani AD. Homocysteine and stroke: Evidence on a causal link from Mendelian randomisation. Lancet 2005; 365:224-32.
116. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72:324-32.
117. Tysoe C, Galinsky D, Robinson D, Brayne CE, Easton DF, Huppert FA, Dening T, Paykel ES, Rubinsztein DC. Analysis of alpha-1 antichymotrypsin, presenilin-1, angiotensin-converting enzyme, and methylenetetrahydrofolate reductase loci as candidates for dementia. Am J Med Genet 1997;74:207-12.
118. Prince JA, Feuk L, Sawyer SL, Gottfries J, Ricksten A, Nagga K, Bogdanovic N, Blennow K, Brookes AJ. Lack of replication of association findings in complex disease: An analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease. Eur J Hum Genet 2001;9:437-44.
119. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GHJ, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G, et al. Plasma homocysteine as a risk factor for vascular disease: The European concerted action project. JAMA 1997;277:1775-81.
120. Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005;4:487-99.
121. Isobe C, Murata T, Sato C, Terayama Y. Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer's disease and Parkinson's disease. Life Sci 2005;77:1836-43.
122. Serot TM, Barbe F, Arning E, Bottiglieri T, Franck P, Montagne P, Nicolas JP. Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: Relation with age and Alzheimer's disease. J Neurol Neurosurg Psychiatry 2005;76:1585-7.
123. Hyland K, Bottiglieri T. Measurement of total plasma and cerebrospinal fluid homocysteine by fluorescence following high-performance liquid chromatography and precolumn derivatization with o-phthaldialdehyde. J Chromatogr 1992;579:55-62.
124. Svardal A, Refsum H, Ueland PM. Determination of in vivo protein binding of homocysteine and its relation to free homocysteine in the liver and other tissues of the rat. J Biol Chem 1986;261:3156-63.
125. Robert K, Santiard-Baron D, Chasse JF, Paly E, Aupetit J, Kamoun P, London J, Janel N. The neuronal SAPK/JNK pathway is altered in a murine model of hyperhomocysteinemia. J Neurochem 2004;89:33-43.
126. Serot JM, Christmann D, Dubost T, Bene MC, Faure GC. CSF-folate levels are decreased in late-onset Alzheimer's disease patients. J Neural Transm 2001;108:93-9.
127. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003;26:137-46.
128. Troen AM. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1140-51.
129. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 2006; 580:2994-3005.
130. Endres M, Ahmadi M, Kruman I, Biniszkiewicz D, Meisel A, Gertz K. Folate deficiency increases postischemic brain injury. Stroke 2005;36:321-5.
131. Fassbender K, Mielke O, Bertsch T, Nafe B, Froschen S, Hennerici M. Homocysteine in cerebral macroangiography and microangiopathy. Lancet 1999; 353:1586-7.
132. Matsui T, Arai H, Yuzuriha T, Yao H, Miura M, Hashimoto S, Higuchi S, Matsushita S, Morikawa M, Kato A, Sasaki H. Elevated plasma homocysteine levels and risk of silent brain infarction in elderly people. Stroke 2001;32:1116-9.
133. Vermeer SE, van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, Breteler MM. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 2002;51:285-9.
134. Hogervorst E, Ribeiro HM, Molyneux A, Budge M, Smith AD. Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease. Arch Neurol 2002;59:787-93.
135. Sachdev P, Parslow R, Salonikas C, Lux O, Wen W, Kumar R, Naidoo D, Christensen H, Jorm A. Homocysteine and the brain in midadult life: Evidence for an increased risk of leukoaraiosis in men. Arch Neurol 2004;61:1369-76.
136. Wright CB, Paik MC, Brown TR, Stabler SP, Allen RH, Sacco RL, DeCarli C. Total homocysteine is associated with white matter hyperintensity volume: The Northern Manhattan Study. Stroke 2005;36:1207-11.
137. Wong A, Mok V, Fan YH, Lam WW, Liang KS, Wong KS. Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. J Neurol 2006; 253:441-7.
138. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 1997;94:5923-8.
139. Bisschops RH, van der Graaf Y, Mali WP, van der Grond J. Elevated levels of plasma homocysteine are associated with neurotoxicity. Atherosclerosis 2004;174:87-92.
140. Kim WK, Pae YS. Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci Lett 1996;216:117-20.
141. Ho PI, Collins SC, Dhitavat S, Ortiz D, Ashline D, Rogers E, Shea TB. Homocysteine potentiates beta-amyloid neurotoxicity: Role of oxidative stress. J Neurochem 2001;78:249-53.
142. White AR, Huang X, Jobling M, Barrow CJ, Beyreuther K, Masters CL, Bush AI, Cappai R. Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: Possible risk factors in the Alzheimer's-type neurodegenerative pathways. J Neurochem 2001;76:1509-20.
143. Gortz P, Hoinkes A, Fleischer W, Otto F, Schwahn B, Wendel U, Siebler M. Implications for hyperhomocysteinemia: Not homocysteine but its oxidized forms strongly inhibit neuronal network activity. J Neurol Sci 2004;218:109-14.
144. Hasegawa T, Ukai W, Jo DG, Xu X, Mattson MP, Nakagawa M, Araki W, Saito T, Yamada T. Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: Implications for the pathogenesis of Alzheimer's disease. J Neurosci Res 2005;80:869-76.
145. Kennedy BP, Bottiglieri T, Arning E, Ziegler MG, Hansen LA, Masliah E. Elevated S-adenosylhomocysteine in Alzheimer brain: Influence on methyltransferases and cognitive function. J Neural Transm 2004;111:547-67.
146. Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S. S-Adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005;28:195-204.
147. Vafai SB, Stock JB. Protein phosphatase 2A methylation: A link between elevated plasma homocysteine and Alzheimer's Disease. FEBS Lett 2002;518:1-4.
148. 6 and one carbon metabolism. J Nutr Health Aging 2002;6:39-42.
149. Scarpa S, Fuso A, D'Anselmi F, Cavallaro RA. Presenilin 1 gene silencing by S-adenosylmethionine: A treatment for Alzheimer disease? FEBS Lett 2003;541:145-8.
150. Chen YF, Li PL, Zou AP. Effect of hyperhomocysteinemia on plasma or tissue adenosine levels and renal function. Circulation 2002;106:1275-81.
151. Riksen NP, Rongen GA, Blom HJ, Russel FG, Boers GH, Smits P. Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia. Cardiovasc Res 2003;59:271-6.
152. Selley ML. Increased homocysteine and decreased adenosine formation in Alzheimer's disease. Neurol Res 2004;26:554-7.
153. 12 deficiency and Alzheimer disease. Neurology 2002; 58:1395-9.
154. Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, Shea TB, Rogers E. Folate deprivation induces neurodegeneration: Roles of oxidative stress and increased homocysteine. Neurobiol Dis 2003;14:32-42.
155. Nagy ZS, Smith MZ, Esiri MM, Barnetson L, Smith AD. Hyperhomocysteinaemia in Alzheimer's disease and expression of cell cycle markers in the brain. J Neurol Neurosurg Psychiatry 2000;69:565-86.
156. Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ, Emokpae R Jr, Gorospe M, Mattson MP. Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 2004;41:549-61.
157. Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000;20:6920-6.
158. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. 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 2002;22:1752-62.
159. Duthie SJ, Narayanan S, Brand GM, Pine L, Grant G. Impact of folate deficiency on DNA stability. J Nutr 2002;132:2444S-9S.
160. Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood 1999;94:959-67.
161. Sai X, Kokame K, Shiraishi H, Kawamura Y, Miyata T, Yanagisawa K, Komano H. The ubiquitin-like domain of Herp is involved in Herp degradation, but not necessary for its enhancement of amyloid beta-protein generation. FEBS Lett 2003;553:151-6.
162. Snowdon DA, Tully CL, Smith CD, Riley KP, Markesbery WR. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: Findings from the Nun study. Am J Clin Nutr 2000;71:993-8.
163. Scott TM, Tucker KL, Bhadelia A, Benjamin B, Patz S, Bhadelia R, Liebson E, Price LL, Griffith J, Rosenberg I, Folstein MF. Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders. Am J Geriatr Psychiatry 2004;12:631-8.
164. Williams JH, Pereira EA, Budge MM, Bradley KM. Minimal hippocampal width relates to plasma homocysteine in community-dwelling older people. Age Ageing 2002;31:440-4.
165. Den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MM. Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 2003;126:170-5.
166. Sachdev PS, Valenzuela M, Wang XL, Looi JC, Brodaty H. Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals. Neurology 2002;58:1539-41.
167. Whalley LJ, Staff RT, Murray AD, Duthie SJ, Collins AR, Lemmon HA, Starr JM, Deary IJ. Plasma vitamin C, cholesterol and homocysteine are associated with grey matter volume determined by MRI in non-demented old people. Neurosci Lett 2003;341:173-6.
168. Seshadri S, Wolf PA, Beiser A, Au R, Wilson PWF, Selhub J, Jacques PF, Rosenberg IR, D'Agostino RB, DeCarli C. Elevated plasma homocysteine levels are associated with subclinical brain injury in healthy adults: Relation to silent cerebral infarcts, white matter hyperintensity and MRI brain volume in the Framingham offspring. AAN Abstracts 2003:(abstract S08.006).
169. White HH, Rowland LP, Araki S, Thompson HL, Cowen D. Homocystinuria. Arch Neurol 1965;13:455-70.
170. Breteler M. Early life circumstances and late life Alzheimer's disease. Epidemiology 2001;12:378-9.
171. Mayeux R. Evil forces and vulnerable brains. Neurology 2000;55:1428-9.
172. 12 for cognition. Cochrane Database Syst Rev 2003:CD004326.
173. 12 for cognition and dementia. Cochrane Database Syst Rev 2003:CD004514.
174. Malouf R, Evans JG. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003:CD004393.
175. 12 Deficiencies. Food Nutr Bull 2008;29:S132-42.
176. Stott DJ, Macintosh G, Lowe GD, Rumley A, McMahon AD, Langhorne P, Tait RC, O'Reilly DS, Spilg EG, MacDonald JB, MacFarlane PW, Westendorp RG. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr 2005;82:1320-6.
177. Aisen PS, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller JW, Green R, Bell K, Sano M. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am J Geriatr Psychiatry 2003;11:246-9.
178. Clinical Trials.gov. VITAL: Vitamins to slow Alzheimer's disease (Homocysteine study) 2003. Available at: http://clinicaltrials.gov/ct/ gui/show/NCT00056225?order=1. Accessed 20 March 2008.
179. 12 and folate supplementation preserve cognitive function of patients with early dementia? 2005. Available at: http://clinicaltrials.gov/ct/gui/show /NCT00164970?order=1. Accessed 20 March 2008.
180. International Standard Randomised Controlled Trial Number Register. VITACOG: Homocysteine and B vitamins in cognitive impairment 2005. Available at: http://www.controlled-trials.com/1SRCTN94410159. Accessed 20 March 2008.
181. Ivan CS, Seshadri S, Beiser A, Au R, Kase CS, Kelly-Hayes M, Wolf PA. Dementia after stroke: The Framingham Study. Stroke 2004;35:1264-8.
182. Leys D, Henon H, Mackowiak-Cordoliani MA, Pasquier F. Poststroke dementia. Lancet Neurol 2005;4:752-9.
183. Manton KC, Gu XL, Ukraintseva SV. Declining prevalence of dementia in the U.S. elderly population. Adv Gerontol 2005;16:30-7.
184. Ganji V, Kafai MR. Population references for plasma total homocysteine concentrations for U.S. children and adolescents in the post-folic acid fortification era. J Nutr 2005;135:2253-6.
185. Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, Friedman TM. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation 2006;113:1335-43.
186. 12 Deficiencies. Food Nutr Bull 2008; 29:S38-51.
187. 12 Deficiencies. Food Nutr Bull 2008; 29:S20-34.
188. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr 2004;24:299-326.
189. Refsum H, Yajnik CS, Gadkari M, Schneede J, Vollset SE, Orning L, Guttormsen AB, Joglekar A, Sayyad MG, Ulvik A, Ueland PM. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutr 2001;74:233-41.
190. 12 status in healthy Iranian adults: The Tehran homocysteine survey (2003-2004)/a cross-sectional population based study. BMC Public Health 2006;6:29.
191. Hettiarachchi M, Liyanage C, Wickremasinghe R, Hilmers DC, Abrahams SA. Prevalence and severity of micronutrient deficiency: A cross-sectional study among adolescents in Sri Lanka. Asia Pac J Clin Nutr 2006; 15:56-63.
192. Dudman NPB. An alternative view of homocysteine. Lancet 1999;354:2072-4.
193. Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygard O, Vollset SE. The Hordaland Homocysteine Study: A community-based study of homocysteine, its determinants, and associations with disease. J Nutr 2006;136:1731S-40S.
194. CFAS. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet 2001;357:169-75.
195. WHO. Mental health global action programme 2002. Available at: http:// www.who.int/mental_health/media/en/265.pdf. Accessed 18 March 2008.
196. WHO. Global strategy on diet, physical activity and health 2004. Available at: http:Hwww.who.int/dietphysicalactivity/strategy/eb11344/ strategy_english_web.pdf. Accessed 18 March 2008.
197. WHO. Preventing chronic diseases. A vital investment 2005. Available at: http://www.who.int/chp/chronic÷sease_report/contents/en /index.html. Accessed 18 March 2008.
198. Bonita R, Mendis S, Truelsen T, Bogousslavsky J, Toole J, Yatsu F. The global stroke initiative. Lancet Neurol 2004;3:391-3.
199. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 1991; 82:239-59.
200. Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology 2005; 65:545-51.
201. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J. Soininen H, Nissinen A. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005:62:1556-60.
202. Shobab LA, Hsiung GY, Feldman HH. Cholesterol in Alzheimer's disease. Lancet Neurol 2005:4:841-52.
203. Roher AE, Esh C, Rahman A, Kokjohn TA, Beach TG. Atherosclerosis of cerebral arteries in Alzheimer disease. Stroke 2004;35:2623-7.
204. Honig LS, Kukull W, Mayeux R. Atherosclerosis and Alzheimer's disease: Analysis of data from the US National Alzheimer's Coordinating Center. Neurology 2005;64:494-500.
205. Ott A, Breteler MMB, deBruyne MC, van Harskamp F, Grobbee DE, Hofman A. Atrial fibrillation and dementia in a population-based study: The Rotterdam Study. Stroke 1997;28:316-21.
206. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 2006;5:64-74.
207. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study. BMJ 2005;330:1360.
208. Tyas SL, White LR, Petrovitch H, Webster Ross G, Foley DJ, Heimovitz HK, Launer LJ. Mid-life smoking and late-life dementia: The Honolulu-Asia Aging Study. Neurobiol Aging 2003;24:589-96.
209. Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT Jr, Mittleman MA, Siscovick DS. Prospective study of alcohol consumption and risk of dementia in older adults. JAMA 2003;289:1405-13.
210. Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R. Alcohol intake and risk of dementia. J Am Geriatr Soc 2004;52:540-6.
211. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Nomiyama K, Kawano H, Ueda K. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: The Hisayama study. Neurology 1995;45:1161-8.
212. Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol 2004;3:343-53.
213. Rovio S, Kareholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol 2005;4:705-11.
214. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 2006; 144:73-81.
215. Podewils LJ, Guallar E. Mens sana in corpore sano. Ann Intern Med 2006;144:135-6.
216. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003:60:940-6.
217. Huang TL, Zandi PP, Tucker KL, Fitzpatrick AL, Kuller LH, Fried LP, Burke CL, Carlson MC. Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4. Neurology 2005;65:1409-14.
218. Buchman AS, Wilson RS, Bienias JL, Shah RC, Evans DA, Bennett DA. Change in body mass index and risk of incident Alzheimer disease. Neurology 2005; 65:892-7.
219. Stewart R, Masaki K, Xue QL, Peila R, Petrovitch H, White LR, Launer LJ. A 32-year prospective study of change in body weight and incident dementia: The Honolulu-Asia aging study. Arch Neurol 2005; 62:55-60.
220. Karp A, Kareholt I, Qiu C, Bellander T, Winblad B, Fratiglioni L. Relation of education and occupation-based socioeconomic status to incident Alzheimer's disease. Am J Epidemiol 2004;159:175-83.
221. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223-9.
222. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230-7.
223. Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol 2004;3:579-87.
224. Engelhart MJ, Ruitenberg A, Meijer J, Kiliaan A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Plasma levels of antioxidants are not associated with Alzheimer's disease or cognitive decline. Dement Geriatr Cogn Disord 2005:19:134-9.
225. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MM. Inflammatory proteins in plasma and the risk of dementia: The Rotterdam study. Arch Neurol 2004:61:668-72.
226. van Oijen M, van der Meer IM, Hofman A, Witteman JC, Koudstaal PJ, Breteler MM. Lipoprotein-associated phospholipase A2 is associated with risk of dementia. Ann Neurol 2005:59:139-44.
227. Hogervorst E, Bandelow S, Combrinck M, Smith AD. Low free testosterone is an independent risk factor for Alzheimer's disease. Exp Gerontol 2004;39:1633-9.
228. Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004;62:188-93.
229. Henderson VW, Hogervorst E. Testosterone and Alzheimer disease: Is it men's turn now? Neurology 2004;62:170-1.
230. Craig MC, Maki PM, Murphy DG. The Women's Health Initiative Memory Study: Findings and implications for treatment. Lancet Neurol 2005;4:190-4.
231. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, Goodman SN. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: A systematic review. Neuroepidemiology 2004; 23:159-69.
232. Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, Breteler MM. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 2000;53:733-7.
233. van Osch LA, Hogervorst E, Combrinck M, Smith AD. Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease. Neurology 2004;62:1967-71.
234. Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Head injury as a risk factor for Alzheimer's disease: The evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 2003;74:857-62.
235. Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, Duara R, Kukull WA, Chui H, Edeki T, Griffith PA, Friedland RP, Bachman D, Farrer L. Depression as a risk factor for Alzheimer disease: The MIRAGE Study. Arch Neurol 2003;60:753-9.
236. Forno GD, Palermo MT, Donohue JE, Karagiozis H, Zonderman AB, Kawas CH. Depressive symptoms, sex, and risk for Alzheimer's disease. Ann Neurol 2005; 57:381-7.
237. Yip AG, Brayne C, Matthews FE. Risk factors for incident dementia in England and Wales: The Medical Research Council Cognitive Function and Ageing Study. A population-based nested case-control study. Age Ageing 2006;35:154-60.
238. Jensen E, Dehlin O, Erfurth EM, Hagberg B, Samuelsson G, Svensson T, Hultberg B. Plasma homocysteine in 80-year-olds - Relationships to medical, psychological and social variables. Arch Gerontol Geriatr 1998;26:215-26.
239. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27:485-91.
240. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: Homocysteine is an early marker. Dement Geriatr Cogn Disord 1999;10:12-20.
241. 12 and folate levels on episodic memory functioning: A population-based study of healthy very old adults. Biol Psychiat 1999;45:1472-80.
242. Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hofman A, Breteler MMB. Total homocysteine and cognitive decline in a community-based sample of elderly subjects - The Rotterdam Study. Am J Epidemiol 1999;150:283-9.
243. Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Jolles J, Clarke R, Breteler MM. Homocysteine and cognitive function in the elderly: The Rotterdam Scan Study. Neurology 2002;59:1375-80.
244. Leblhuber F, Walli J, Artner-Dworzak E, Vrecko K, Widner B, Reibnegger G, Fuchs D. Hyperhomocysteinemia in dementia. J Neural Transm 2000;107:1469-74.
245. 12, C and folate concentrations in the New Mexico elder health survey: Correlations with cognitive and affective functions. J Am Coll Nutr 2000;19:68-76.
246. Ravaglia G, Forti P, Maioli F, Vettori C, Grossi G, Bargossi AM, Caldarera M, Franceschi C, Facchini A, Mariani E, Cavalli G. Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment. Mech Ageing Dev 2000;121:251-61.
247. Ravaglia G, Forti P, Maioli F, Zanardi V, Dalmonte E, Grossi G, Cucinotta D, Macini P, Caldarera M. Blood homocysteine and vitamin B levels are not associated with cognitive skills in healthy normally ageing subjects. J Nutr Health Aging 2000;4:218-22.
248. Ravaglia G, Forti P, Maioli F, Scali RC, Saccheitti L, Talerico T, Mantovani V, Bianchin M. Homocysteine and cognitive performance in healthy elderly subjects. Arch Gerontol Geriatr Suppl 2004:349-57.
249. 12 and folic acid on cognitive performance in old age: A population-based study. Dev Neuropsychol 2001;20:565-71.
250. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2001;73:927-33.
251. Bottiglieri T, Parnetti L, Arning E, Ortiz T, Amici S, Lanari A, Gallai V. Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: A study in an Italian population with dementia. Mech Ageing Dev 2001;122:2013-23.
252. 12, and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study. Gerontology 2001;47:324-9.
253. 12 and folate status on cognitive functioning in very old age. Biol Psychol 2001;56:247-65.
254. Tripathi M, Sheshadri S, Padma MV, Jain S, Meheshwari MC, Behari M. Serum cobalamin levels in dementias. Neurol India 2001;49:284-6.
255. Budge MM, De Jager C, Hogervorst E, Smith AD. Total plasma homocysteine, age, systolic blood pressure and cognitive performance in older people. J Am Geriatr Soc 2002;50:2014-8.
256. McIlroy SP, Dynan KB, Lawson JT, Patterson CC, Passmore AP. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke 2002;33:2351-6.
257. Selley ML, Close DR, Stern SE. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging 2002;23:383-8.
258. de Luis DA, Fernandez N, Arranz M, Allen R, Izaola O. Total homocysteine and cognitive deterioration in people with type 2 diabetes. Diabetes Res Clin Pract 2002;55:185-90.
259. Eto K, Asada T, Arima K, Makifuchi T, Kimura H. Brain hydrogen sulfide is severely decreased in Alzheimer's disease. Biochem Biophys Res Commun 2002; 293:1485-8.
260. Stewart R, Asonganyi B, Sherwood R. Plasma homocysteine and cognitive impairment in an older British African-Caribbean population. J Am Geriatr Soc 2002;50:1227-32.
261. 12 levels in elderly patients with progressive dementia. Am J Geriatr Psychiatry 2002;10:321-7.
262. 12 deficiency in elderly using Title IIIc nutrition services. Am J Clin Nutr 2003; 77:211-20.
263. Whitmer RA, Haan MN, Miller JW, Yaffe K. Hormone replacement therapy and cognitive performance: The role of homocysteine. J Gerontol A Biol Sci Med Sci 2003;58:M324-M30.
264. Ravaglia G, Forti P, Maioli F, Muscari A, Sacchetti L, Arnone G, Nativio V, Talerico T, Mariani E. Homocysteine and cognitive function in healthy elderly community dwellers in Italy. Am J Clin Nutr 2003;77:668-73.
265. McCaddon A, Hudson P, Hill D, Barber J, Lloyd A, Davies G, Regland B. Alzheimer's disease and total plasma aminothiols. Biol Psychiatry 2003;53:254-60.
266. Religa D, Styczynska M, Peplonska B, Gabryelewicz T, Pfeffer A, Chodakowska M, Luczywek E, Wasiak B, Stepien K, Golebiowski M, Winblad B, Barcikowska M. Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord 2003;16:64-70.
267. VITAL Trial Collaborative Group. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med 2003;254:67-75.
268. Nagga K, Rajani R, Mardh E, Borch K, Mardh S, Marcusson J. Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia. Dement Geriatr Cogn Disord 2003;16:269-75.
269. Storey SG, Suryadevara V, Aronow WS, Ahn C. Association of plasma homocysteine in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease. J Gerontol A Biol Sci Med Sci 2003;58:M1135-6.
270. 6 and folate intake in Alzheimer's disease and healthy aging. J Nutr Health Aging 2003;7:160-5.
271. Miller JW, Green R, Ramos MI, Allen LH, Mungas DM, Jagust WJ, Haan MN. Homocysteine and cognitive function in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2003;78:441-7.
272. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer's disease. Neurobiol Aging 2003;24:903-7.
273. Sachdev PS, Valenzuela MJ, Brodaty H, Wang XL, Looi J, Lorentz L, Howard L, Jones M, Zagami AS, Gillies D, Wilcken DE. Homocysteine as a risk factor for cognitive impairment in stroke patients. Dement Geriatr Cogn Disord 2003;15:155-62.
274. Tsolaki M, Kartali N. Folic acid and Alzheimer's disease. Int J Geriatr Psychiatry 2003;18:187-8.
275. 12 and folate in patients with dementia. Int J Geriatr Psychiatry 2004;19:365-70.
276. Anello G, Gueant-Rodriguez RM, Bosco P, Gueant JL, Romano A, Namour B, Spada R, Caraci F, Pourie G, Daval JL, Ferri R. Homocysteine and methylenetetrahydrofolate reductase polymorphism in Alzheimer's disease. Neuroreport 2004;15:859-61.
277. 12 and folate in Alzheimer's patients and healthy Arabs in Israel. J Neurol Sci 2004;227:109-13.
278. Wright CB, Lee HS, Paik MC, Stabler SP, Allen RH, Sacco RL. Total homocysteine and cognition in a tri-ethnic cohort: The Northern Manhattan Study. Neurology 2004;63:254-60.
279. 12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr 2004;80:114-22.
280. Gallucci M, Zanardo A, De Valentin L, Vianello A. Homocysteine in Alzheimer disease and vascular dementia. Arch Gerontol Geriatr Suppl 2004:195-200.
281. 12 and folate in vascular dementia and in Alzheimer disease. Clin Chem Lab Med 2004;42:1032-5.
282. Malaguarnera M, Bella R, Alagona G, Ferri R, Carnemolla A, Pennisi G. Helicobacter pylori and Alzheimer's disease: A possible link. Eur J Intern Med 2004; 15:381-6.
283. 12, folate, homocysteine and dementia: Are they really related? Arch Gerontol Geriatr 2005; 40:139-46.
284. Aleman A, Muller M, de Haan EH, van der Schouw YT. Vascular risk factors and cognitive function in a sample of independently living men. Neurobiol Aging 2005;26:485-90.
285. Adunsky A, Arinzon Z, Fidelman Z, Krasniansky I, Arad M, Gepstein R. Plasma homocysteine levels and cognitive status in long-term stay geriatric patients: A cross-sectional study. Arch Gerontol Geriatr 2005; 40:129-38.
286. Clark MS, Guthrie JR, Dennerstein L. Hyperhomocysteinemia is associated with lower performance on memory tasks in post-menopausal women. Dement Geriatr Cogn Disord 2005;20:57-62.
287. 12 and folate in Alzheimer's and vascular dementias: The paradoxical effect of the superimposed type II diabetes mellitus condition. Clin Chim Acta 2005;359:163-70.
288. Guidi I, Galimberti D, Venturelli E, Lovati C, del Bo R, Fenoglio C, Gatti A, Dominici R, Galbiati S, Virgilio R, Pomati S, Comi GP, Mariani C, Forloni G, Bresolin N, Scarpini E. Influence of the Glu298Asp polymorphism of NOS3 on age at onset and homocysteine levels in Alzheimer's disease patients. Neurobiol Aging 2005;26:789-94.
289. de Silva HA, Gunatilake SB, Johnston C, Warden D, Smith AD. Medial temporal lobe atrophy, apolipoprotein genotype, and plasma homocysteine in Sri Lankan patients with Alzheimer's disease. Exp Aging Res 2005;31:345-54.
290. Irizarry MC, Gurol ME, Raju S, Diaz-Arrastia R, Locascio JJ, Tennis M, Hyman BT, Growdon JH, Greenberg SM, Bottiglieri T. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology 2005;65:1402-8.
291. Lautenschlager NT, Flicker L, Vasikaran S, Leedman P, Almeida OP. Subjective memory complaints with and without objective memory impairment: Relationship with risk factors for dementia. Am J Geriatr Psychiatry 2005;13:731-4.
292. Lewis MS, Miller LS, Johnson MA, Dolce EB, Allen RH, Stabler SP. Elevated methylmalonic acid is related to cognitive impairment in older adults enrolled in an elderly nutrition program. J Nutr Elder 2005;24:47-65.
293. Manders M, Vasse E, de Groot LC, van Staveren WA, Bindels JG, Blom HJ, Hoefnagels WH. Homocysteine and cognitive function in institutionalised elderly. A cross-sectional analysis. Eur J Nutr 2005.
294. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Tettamanti M, Lucca U. Homocysteine and B vitamins in mild cognitive impairment and dementia. Clin Chem Lab Med 2005;43:1096-100.
295. 12, serum folate, and cognitive change between 11 and 79 years. J Neurol Neurosurg Psychiatry 2005;76:291-2.
296. Zhang YD, Ke XY, Shen W, Liu Y. Relationship of homocysteine and gene polymorphisms of its related metabolic enzymes with Alzheimer's disease. Chin Med Sci J 2005;20:247-51.
297. Lewerin C, Matousek M, Steen G, Johansson B, Steen B, Nilsson-Ehle H. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: A placebo-controlled randomized study. Am J Clin Nutr 2005;81:1155-62.
298. Mulder C, Schoonenboom NS, Jansen EE, Verhoeven NM, van Kamp GJ, Jakobs C, Scheltens P. The transmethylation cycle in the brain of Alzheimer patients. Neurosci Lett 2005;386:69-71.
299. Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N, Scarpini E. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 2006;27:262-9.
300. Wilhelm J, Bayerlein K, Hillemacher T, Reulbach U, Frieling H, Kromolan B, Degner D, Kornhuber J, Bleich S. Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism. J Neural Transm 2006;113:357-63.
301. Durga J, van Boxtel MP, Schouten EG, Bots ML, Kok FJ, Verhoef P. Folate and the methylenetetrahydrofolate reductase 677C → T mutation correlate with cognitive performance. Neurobiol Aging 2006;27:334-43.
302. Nilsson SE, Evrin PE, Tryding N, Berg S, McClearn G, Johansson B. Biochemical values in persons older than 82 years of age: Report from a population-based study of twins. Scand J Clin Lab Invest 2003;63:1-13.
303. Annerbo S, Wahlund LO, Lokk J. The relation between homocysteine levels and development of Alzheimer's disease in mild cognitive impairment patients. Dement Geriatr Cogn Disord 2005;20:209-14.
304. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between cerebrospinal fluid biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: A follow-up study. Lancet Neurol 2006;5:228-34.
305. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Pantieri G, Mariani E. Conversion of mild cognitive impairment to dementia: Predictive role of mild cognitive impairment subtypes and vascular risk factors. Dement Geriatr Cogn Disord 2006;21:51-8.