Skip to main content

Advertisement

SpringerLink
Log in

Diet, cognition, and Alzheimer’s disease: food for thought

  • Review
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Introduction

The prevention of Alzheimer’s disease (AD) has become a real challenge due to its rising prevalence and the lack of an effective cure. Diet and nutrients have gained significant interest as potentially modifiable protective factors.

Purpose

The aim of this review is to provide an updated summary of evidence related to the effect of diet and nutritional factors on the risk of AD and cognitive aging, and discuss the potential mechanisms and confounding factors involved.

Methods

A search was conducted in Medline and Web of Knowledge for epidemiological and clinical studies in the international literature from January 2000 to February 2013 using combinations of the following keywords: “Alzheimer’s disease”, “mild cognitive impairment”, “cognitive function”, “dietary factors”, “omega-3”, “antioxidants”, “B vitamins”, “dietary patterns”, and “Mediterranean diet”.

Results and conclusion

Data from observational studies point to a protective role for certain nutrients, such as omega-3 fatty acids, antioxidants or B vitamins, and dietary patterns (Mediterranean diet). However, data from randomized controlled trials do not show a consistent effect. Whether confounding factors such as age, disease stage, other dietary components, cooking processes, and other methodological issues explain the divergent results remains to be established. Moreover, if certain nutrients protect against dementia, it is as yet unknown whether they may have a general effect on brain vascular health or directly interfere with the etiopathogenesis of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

DASH:

Dietary approaches to stop hypertension

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

FCT:

Food composition table

FFQ:

Food frequency questionnaire

Hcy:

Homocysteine

HEI:

Health eating index

MCI:

Mild cognitive impairment

MeDi:

Mediterranean diet

n-3:

Omega-3

n-6:

Omega-6

PUFA:

Polyunsaturated fatty acid

References

  1. Alzheimer’s Association (2012) 2012 Alzheimer’s disease facts and figures. Alzheimer’s Dement 8:131–168

    Google Scholar 

  2. Wimo A, Prince M (2010) World Alzheimer report 2010: the global economic impact of dementia. ADI

  3. Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa SG, Plassman BL, Kukull WA (2011) National estimates of the prevalence of Alzheimer’s disease in the United States. Alzheimer’s Dement 7:61–73

    Google Scholar 

  4. Luchsinger J, Mayeux R (2004) Dietary factors and Alzheimer’s disease. Lancet Neurol 3:579–587

    Google Scholar 

  5. Morris M (2009) The role of nutrition in Alzheimer’s disease: epidemiological evidence. Eur J Neurol 16:1–7

    Google Scholar 

  6. Yehuda S, Rabinovitz S, Mostofsky DI (2005) Essential fatty acids and the brain: from infancy to aging. Neurobiol Aging 26:98–102

    Google Scholar 

  7. Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N (2001) Physiological compartmental analysis of α-linolenic acid metabolism in adult humans. J Lipid Res 42:1257–1265

    CAS  Google Scholar 

  8. Mozaffarian D, Wu JHY (2011) Omega-3 fatty acids and cardiovascular disease. J Am Coll Cardiol 58:2047–2067

    CAS  Google Scholar 

  9. Laitinen M, Ngandu T, Rovio S, Helkala E, Uusitalo U, Viitanen M (2006) Fat intake at midlife and risk of dementia and Alzheimer’s disease: a population-based study. Dement Geriatr Cogn Disord 22:99–107

    CAS  Google Scholar 

  10. Morris M, Evans D, Bienias J, Tangney C, Wilson R (2004) Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology 62:1573–1579

    CAS  Google Scholar 

  11. Solfrizzi V, Colacicco A, Introno A, Capurso C, Torres F, Rizzo C (2006) Dietary intake of unsaturated fatty acids and age-related cognitive decline: a 8.5-year follow-up of the Italian Longitudinal Study on Aging. Neurobiol Aging 27:1694–1704

    CAS  Google Scholar 

  12. Ubeda N, Achon M, Varela Moreiras G (2012) Omega 3 fatty acids in the elderly. Br J Nutr 107:S137–S151

    CAS  Google Scholar 

  13. Vercambre MN, Boutron-Ruault MC, Ritchie K, Clavel-Chapelon F, Berr C (2009) Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women. Br J Nutr 102:419–427

    CAS  Google Scholar 

  14. Solfrizzi V, Colacicco A, D’Introno A, Capurso C, Del Parigi A, Capurso S (2006) Dietary fatty acids intakes and rate of mild cognitive impairment. The Italian longitudinal study on aging. Exp Gerontol 41:619–627

    CAS  Google Scholar 

  15. Barberger Gateau P, Peres K, Letenneur L, Deschamps V, Peres K, Dartigues J, Renaud S (2002) Fish, meat, and risk of dementia: cohort study. BMJ 325:932–933

    Google Scholar 

  16. Morris M, Evans D, Bienias J, Tangney C, Bennett D, Wilson R (2003) Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 60:940–946

    Google Scholar 

  17. Huang T, Zandi P, Tucker K, Fitzpatrick A, Kuller L, Fried L (2005) Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon 4. Neurology 65:1409–1414

    CAS  Google Scholar 

  18. Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues J (2007) Dietary patterns and risk of dementia—the three-city cohort study. Neurology 69:1921–1930

    CAS  Google Scholar 

  19. Devore E, Grodstein F, van Rooij FJA, Hofman A, Rosner B, Breteler MMB, Stampfer M (2009) Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk. Am J Clin Nutr 90:170–176

    CAS  Google Scholar 

  20. Morris M, Evans D, Tangney C, Bienias J, Wilson R (2005) Fish consumption and cognitive decline with age in a large community study. Arch Neurol 62:1849–1853

    Google Scholar 

  21. van Gelder B, Tijhuis M, Kalmijn S, Kromhout D (2007) Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr 85:1142–1147

    Google Scholar 

  22. Eskelinen M, Ngandu T, Helkala E, Tuomilehto J, Nissinen A, Soininen H (2008) Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry 23:741–747

    Google Scholar 

  23. Kalmijn S, van Boxtel M, Ocke M, Verschuren W, Kromhout D, Launer L (2004) Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 62:275–280

    CAS  Google Scholar 

  24. Raji C, Erickson K, Lopez O, Kuller L, Gach M, Thompson P, Riverol M, Becker M (2011) Regular fish consumption is associated with larger gray matter volumes and reduced risk for cognitive decline in the cardiovascular health study. Annual Meeting of the Radiological Society of North America

  25. Tully A, Roche H, Doyle R, Fallon C, Bruce I, Lawlor B (2003) Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer’s disease: a case-control study. Br J Nutr 89:483–489

    CAS  Google Scholar 

  26. Conquer J, Tierney M, Zecevic J, Bettger W, Fisher R (2000) Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids 35:1305–1312

    CAS  Google Scholar 

  27. Corrigan FM, Horrobin DF, Skinner ER, Besson JAO, Cooper MB (1998) Abnormal content of n − 6 and n − 3 long-chain unsaturated fatty acids in the phosphoglycerides and cholesterol esters of parahippocampal cortex from Alzheimer’s disease patients and its relationship to acetyl CoA content. Int J Biochem Cell Biol 30:197–207

    CAS  Google Scholar 

  28. Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, DeCarli C, Wolf PA, Vasan RS, Robins SJ, Seshadri S (2012) Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology 78:658–664

    CAS  Google Scholar 

  29. Samieri C, Maillard P, Crivello F, Proust-Lima C, Peuchant E, Helmer C, Amieva H, Allard M, Dartigues JF, Cunnane S, Mazoyer B, Barberger-Gateau P (2012) Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology 79:642–650

    CAS  Google Scholar 

  30. Schaefer E, Bongard V, Beiser A, Lamon-Fava S, Robins S, Au R (2006) Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease—the Framingham heart study. Arch Neurol 63:1545–1550

    Google Scholar 

  31. Kroger E, Verreault R, Carmichael P, Lindsay J, Julien P, Dewailly E (2009) Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging. Am J Clin Nutr 90:184–192

    CAS  Google Scholar 

  32. Laurin D, Verreault R, Lindsay J, Dewailly E, Holub B (2003) Omega-3 fatty acids and risk of cognitive impairment and dementia. J Alz Dis 5:315–322

    CAS  Google Scholar 

  33. Beydoun M, Kaufman J, Satia J, Rosamond W, Folsom A (2007) Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the atherosclerosis risk in communities study. Am J Clin Nutr 85:1103–1111

    CAS  Google Scholar 

  34. Heude B, Ducimetiere P, Berr C (2003) Cognitive decline and fatty acid composition of erythrocyte membranes—the EVA study. Am J Clin Nutr 77:803–808

    CAS  Google Scholar 

  35. Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, Fox HC (2008) n-3 Fatty acid erythrocyte membrane content, APOE epsilon4, and cognitive variation: an observational follow-up study in late adulthood. J Am Clin Nutr 87:449–454

    CAS  Google Scholar 

  36. Boston P, Bennett A, Horrobin D, Bennett C (2004) Ethyl-EPA in Alzheimer’s disease—a pilot study. Prostaglandins Leukot Essent Fatty Acids 71:341–346

    CAS  Google Scholar 

  37. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: omegAD study—a randomized double-blind trial. Arch Neurol 63:1402

    Google Scholar 

  38. Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y (2006) Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56:159–164

    CAS  Google Scholar 

  39. Chiu C, Su K, Cheng T, Liu H, Chang C, Dewey M (2008) The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 32:1538–1544

    CAS  Google Scholar 

  40. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Weiner M, Shinto L, Aisen PS (2010) Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease. JAMA 304:1903–1911

    CAS  Google Scholar 

  41. Lee L, Shahar S, Chin A (2013) Docosahexaenoic acid-concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology 225:605–612

    CAS  Google Scholar 

  42. van de Rest O, Geleijnse J, Kok F, van Staveren W, Dullemeijer C, OldeRikkert M (2008) Effect of fish oil on cognitive performance in older subjects—a randomized, controlled trial. Neurology 71:430–438

    Google Scholar 

  43. Dangour A, Allen E, Elbourne D, Fasey N, Fletcher A, Hardy P (2010) Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am J Clin Nutr 91:1725–1732

    CAS  Google Scholar 

  44. Andreeva V, Kesse Guyot E, Barberger Gateau P, Fezeu L, Hercberg S, Galan P (2011) Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr 94:278–286

    CAS  Google Scholar 

  45. Richter Y, Herzog Y, Cohen T, Steinhart Y (2010) The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study. Clin Interv Aging 5:313–316

    CAS  Google Scholar 

  46. Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N, Stedman M (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimer’s Dement 6:456–464

    CAS  Google Scholar 

  47. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR (1997) Brain infarction and the clinical expression of alzheimer disease: the nun study. JAMA 277:813–817

    CAS  Google Scholar 

  48. Conklin SM, Gianaros PJ, Brown SM, Yao JK, Hariri AR, Manuck SB, Muldoon MF (2007) Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett 421:209–212

    CAS  Google Scholar 

  49. Wassall SR, Brzustowicz MR, Shaikh SR, Cherezov V, Caffrey M, Stillwell W (2004) Order from disorder, corralling cholesterol with chaotic lipids: the role of polyunsaturated lipids in membrane raft formation. Chem Phys Lipids 132:79–88

    CAS  Google Scholar 

  50. Jicha GA, Markesbery WR (2010) Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease. Clin Interv Aging 5:45–61

    CAS  Google Scholar 

  51. Kiecolt Glaser J, Belury M, Andridge R, Malarkey W, Hwang B, Glaser R (2012) Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial. Brain Behav Immun 26:988–995

    CAS  Google Scholar 

  52. Bazan NG (2013) The docosanoid neuroprotectin D1 induces homeostatic regulation of neuroinflammation and cell survival. Prostaglandins Leukot Essent Fatty Acids 88:127–129

    CAS  Google Scholar 

  53. Hashimoto M, Hossain S, Shimada T, Sugioka K, Yamasaki H, Fujii Y, Ishibashi Y, Oka J, Shido O (2002) Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer’s disease model rats. J Neurochem 81:1084–1091

    CAS  Google Scholar 

  54. Grimm MOW, Kuchenbecker J, Grösgen S, Burg VK, Hundsdörfer B, Rothhaar TL, Friess P, de Wilde MC, Broersen LM, Penke B, Péter M, Vígh L, Grimm HS, Hartmann T (2011) Docosahexaenoic acid reduces amyloid Beta production via multiple pleiotropicmechanisms. J Biol Chem 286:14028–14039

    CAS  Google Scholar 

  55. Lim G, Calon F, Morihara T, Yang F, Teter B, Ubeda O (2005) A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 25:3032–3040

    CAS  Google Scholar 

  56. Hashimoto M, Shahdat HM, Yamashita S, Katakura M, Tanabe Y, Fujiwara H, Gamoh S, Miyazawa T, Arai H, Shimada T, Shido O (2008) Docosahexaenoic acid disrupts in vitro amyloid B1-40 fibrillation and concomitantly inhibits amyloid levels in cerebral cortex of Alzheimer’s disease model rats. J Neurochem 107:1634–1646

    CAS  Google Scholar 

  57. Hossain S, Hashimoto M, Katakura M, Miwa K, Shimada T, Shido O (2009) Mechanism of docosahexaenoic acid-induced inhibition of in vitro AB1-B42 fibrillation and AB1-B42-induced toxicity in SH-S5Y5 cells. J Neurochem 111:568–579

    CAS  Google Scholar 

  58. Gu Y, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N (2012) Nutrient intake and plasma beta-amyloid. Neurology 78:1832–1840

    CAS  Google Scholar 

  59. Bonda D, Wang X, Perry G, Nunomura A, Tabaton M, Zhu X (2010) Oxidative stress in Alzheimer disease: a possibility for prevention. Neuropharmacology 59:290–294

    CAS  Google Scholar 

  60. Hermsdorff HHM, Puchau B, Bressan J (2012) Vitamin C and fibre consumption from fruits and vegetables improves oxidative stress markers in healthy young adults. Br J Nutr 107:1119–1127

    CAS  Google Scholar 

  61. Xaplanteris P, Vlachopoulos C, Pietri P, Terentes Printzios D, Kardara D (2012) Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr Res 32:390–394

    CAS  Google Scholar 

  62. Beking K, Vieira A (2010) Flavonoid intake and disability-adjusted life years due to Alzheimer’s and related dementias: a population-based study involving twenty-three developed countries. Public Health Nutr 13:1403–1409

    Google Scholar 

  63. Zandi P, Anthony J, Khachaturian A, Stone S, Gustafson D, Tschanz J (2004) Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements—the Cache County study. Arch Neurol 61:82–88

    Google Scholar 

  64. Jama J, Launer L, Witteman J, denBreeijen J, Breteler M, Grobbee D (1996) Dietary antioxidants and cognitive function in a population-based sample of older persons—the Rotterdam study. Am J Epidemiol 144:275–280

    CAS  Google Scholar 

  65. Ortega R, Requejo A, Lopez-Sobaler A, Andres P, Navia B, Perea J (2002) Cognitive function in elderly people is influenced by vitamin E status. J Nutr 132:2065–2068

    CAS  Google Scholar 

  66. Grodstein F, Chen J, Willett W (2003) High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Am J Clin Nutr 77:975–984

    CAS  Google Scholar 

  67. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues J (2000) Intake of flavonoids and risk of dementia. Eur J Epidemiol 16:357–363

    CAS  Google Scholar 

  68. Engelhart M, Geerlings M, Ruitenberg A, van Swieten J, Holman A, Witteman J (2002) Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 287:3223–3229

    CAS  Google Scholar 

  69. Laurin D, Masaki K, Foley D, White L, Launer L (2004) Midlife dietary intake of antioxidants and risk of late-life incident dementia—The Honolulu-Asia aging study. Am J Epidemiol 159:959–967

    Google Scholar 

  70. Morris M, Evans D, Tangney C, Bienias J, Wilson R, Aggarwal N (2005) Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 81:508–514

    CAS  Google Scholar 

  71. Dai Q, Borenstein A, Wu Y, Jackson J, Larson E (2006) Fruit and vegetable juices and Alzheimer’s disease: the Kame project. Am J Med 119:751–759

    CAS  Google Scholar 

  72. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues J, Barberger-Gateau P (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165:1364–1371

    CAS  Google Scholar 

  73. Devore E, Grodstein F, van Rooij F, Hofman A, Stampfer M, Witteman J (2010) Dietary antioxidants and long-term risk of dementia. Arch Neurol 67:819–825

    Google Scholar 

  74. Masaki K, Losonczy K, Izmirlian G, Foley D, Ross G, Petrovitch H (2000) Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 54:1265–1272

    CAS  Google Scholar 

  75. Fillenbaum G, Kuchibhatla M, Hanlon J, Artz M, Pieper C, Schmader K (2005) Dementia and Alzheimer’s disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother 39:2009–2014

    CAS  Google Scholar 

  76. Morris M, Evans D, Bienias J, Tangney C, Bennett D, Aggarwal N (2002) Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease on a biracial community study. JAMA 287:3230–3237

    CAS  Google Scholar 

  77. Luchsinger J, Tang M, Shea S, Mayeux R (2003) Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 60:203–208

    Google Scholar 

  78. Corrada M, Kawas C, Hallfrisch J, Muller D, Brookmeyer R (2005) Reduced risk of Alzheimer’s disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimer’s Dement 1:11–18

    CAS  Google Scholar 

  79. Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N, Scarpini E (2006) Oxidative imbalance in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 27:262–269

    CAS  Google Scholar 

  80. Baldeiras I, Santana I, Proença MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR (2010) Oxidative damage and progression to Alzheimer’s Disease in patients with mild cognitive impairment. J Alz Dis 21:1165–1177

    CAS  Google Scholar 

  81. Guglielmotto M, Giliberto L, Tamagno E, Tabaton M (2010) Oxidative stress mediates the pathogenic effect of different Alzheimer’s disease risk factors. Front Aging Neurosci 2:1–8

    Google Scholar 

  82. Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, Smith MA (2000) Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. J Neuropathol Exp Neurol 59:1011–1017

    CAS  Google Scholar 

  83. Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM- (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21:4183–4187

    CAS  Google Scholar 

  84. Butterfield DA, Reed T, Perluigi M, De Marco C, Coccia R, Cini C, Sultana R (2006) Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci Lett 397:170–173

    CAS  Google Scholar 

  85. Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64:1152–1156

    CAS  Google Scholar 

  86. Pratico D, Clark CM, Liun F, Lee VY-, Trojanowski JQ (2002) Increase of brain oxidative stress in Mild Cognitive Impairment: a possible predictor of Alzheimer disease. Arch Neurol 59:972–976

    Google Scholar 

  87. Lloret A, Badia M, Mora N, Pallardo F, Alonso M, Vina J (2009) Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimer’s Dis 17:143–149

    CAS  Google Scholar 

  88. Arlt S, Mueller Thomsen T, Beisiegel U, Kontush A (2012) Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer’s disease. Neurochem Res 37:2706–2714

    CAS  Google Scholar 

  89. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P, Alzheimer’s Disease Cooperative Study (2012) Antioxidants for alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69:836–841

    Google Scholar 

  90. Petersen R, Thomas R, Grundman M, Bennett D, Doody R, Ferris S (2005) Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 352:2379–2388

    CAS  Google Scholar 

  91. Krikorian R, Nash T, Shidler M, Shukitt-Hale B, Joseph J (2010) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr 103:730–734

    CAS  Google Scholar 

  92. Kang J, Cook N, Manson J, Buring J, Grodstein F (2006) A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med 166:2462–2468

    CAS  Google Scholar 

  93. Grodstein F, Kang J, Glynn R, Cook N, Gaziano M (2007) A Randomized trial of beta carotene supplementation and cognitive function in men—the physicians’ health study II. Arch Intern Med 167:2184–2190

    CAS  Google Scholar 

  94. Kang J, Cook N, Manson J, Buring J, Albert C, Grodstein F (2009) Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease The Women’s Antioxidant and Cardiovascular Study. Circulation 119:2772–2780

    CAS  Google Scholar 

  95. Bjelakovic G, Nikolova D, Gluud L, Simonetti R, Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev (3):CD007176

  96. Bjelakovic G, Nikolova D, Gluud L, Simonetti RG, Gluud C (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA: The. J Am Med Assoc 297:842–857

    CAS  Google Scholar 

  97. Miller E, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may Increase all-cause mortality. Ann Intern Med 142:37–46

    CAS  Google Scholar 

  98. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomized trials. Lancet 361:2017–2023

    CAS  Google Scholar 

  99. Bell S, Grochoski G (2008) How safe is vitamin E supplementation? Crit Rev Food Sci Nutr 48:760–774

    CAS  Google Scholar 

  100. Abner E, Schmitt F, Mendiondo M, Marcum J, Kryscio R (2011) Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci 4:158–170

    CAS  Google Scholar 

  101. Pavlik VN, Doody RS, Rountree SD, Darby EJ (2009) Vitamin E use is associated with improved survival in an Alzheimer’s disease cohort. Dement Geriatr Cogn Disord 28:536–540

    CAS  Google Scholar 

  102. Sano M, Ernesto C, Thomas R, Klauber M, Schafer K, Grundman M (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med 336:1216–1222

    CAS  Google Scholar 

  103. Morris M, Tangney C (2011) A potential design flaw of randomized trials of vitamin supplements. JAMA 305:1348–1349

    CAS  Google Scholar 

  104. Bryan J, Calvaresi E, Hughes D (2002) Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr 132:1345–1356

    CAS  Google Scholar 

  105. Morris M, Evans D, Schneider J, Tangney C, Bienias J, Aggarwal N (2006) Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer’s disease. J Alzheimer’s Dis 9:435–443

    Google Scholar 

  106. Luchsinger J, Tang M, Miller J, Green R, Mayeux R (2007) Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 64:86–92

    Google Scholar 

  107. Nelson C, Wengreen H, Munger R, Corcoran C, Cache C (2009) Dietary folate, vitamin B-12, vitamin B-6 and incident Alzheimer’s disease: the Cache County Memory, Health and Aging Study. J Nutr Health Aging 13:899–905

    CAS  Google Scholar 

  108. Morris M, Evans D, Bienias J, Tangney C, Hebert L, Scherr P (2005) Dietary folate and vitamin B-12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 62:641–645

    Google Scholar 

  109. Tucker K, Qiao N, Scott T, Rosenberg I, Spiro A (2005) High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans affairs normative aging study. Am J Clin Nutr 82:627–635

    CAS  Google Scholar 

  110. Hooshmand B, Solomon A, Kareholt I, Leiviska J, Rusanen M, Ahtiluoto S (2010) Homocysteine and holotranscobalamin and the risk of Alzheimer disease a longitudinal study. Neurology 75:1408–1414

    CAS  Google Scholar 

  111. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M (2004) Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr 80:114–122

    CAS  Google Scholar 

  112. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N (2005) Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 82:636–643

    CAS  Google Scholar 

  113. Wang H, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L (2001) Vitamin B-12 and folate in relation to the development of Alzheimer’s disease. Neurology 56:1188–1194

    CAS  Google Scholar 

  114. Duthie S, Whalley L, Collins A, Leaper S, Berger K, Deary I (2002) Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 75:908–913

    CAS  Google Scholar 

  115. Kado D, Karlamangla A, Huang M, Troen A, Rowe J, Selhub J (2005) Homocysteine versus the vitamins folate, B-6, and B-12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur studies of successful aging. Am J Med 118:161–167

    CAS  Google Scholar 

  116. de Lau L, Refsum H, Smith A, Johnston C, Breteler M (2007) Plasma folate concentration and cognitive performance: Rotterdam scan study. Am J Clin Nutr 86:728–734

    Google Scholar 

  117. Faux N, Ellis K, Porter L, Fowler C, Laws S, Martins R, Pertile K, Rembach A, Rowe C, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Villemagne V, Ward V, Ames D, Masters C, Bush A (2011) Homocysteine, vitamin B12, and folic acid levels in Alzheimer’s disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian imaging biomarker lifestyle study. J Alz Dis 27:909–922

    CAS  Google Scholar 

  118. Clarke R, Evans JG, Schneede J, Nexo E, Bates C, Fletcher A, Prentice A, Johnston C, Ueland PM, Refsum H, Sherliker P, Birks J, Whitlock G, Breeze E, Scott JM (2004) Vitamin B12 and folate deficiency in later life. Age Ageing 33:34–41

    Google Scholar 

  119. Clarke R, Smith A, Jobst K, Refsum H, Sutton L, Ueland P (1998) Folate, vitamin B-12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449–1455

    CAS  Google Scholar 

  120. Haan M, Miller J, Aiello A, Whitmer R, Jagust W, Mungas D (2007) Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr 85:511–517

    CAS  Google Scholar 

  121. Nilsson K, Gustafson L, Hultberg B (2001) Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry 16:609–614

    CAS  Google Scholar 

  122. Sommer B, Hoff A, Costa M (2003) Folic acid supplementation in dementia: a preliminary report. J Geriatr Psychiatry Neurol 16:156–159

    Google Scholar 

  123. Aisen P, Schneider L, Sano M, Diaz-Arrastia R, van Dyck C, Weiner M (2008) High-dose B vitamin supplementation and cognitive decline in Alzheimer disease—a randomized controlled trial. JAMA 300:1774–1783

    CAS  Google Scholar 

  124. Kwok T, Lee J, Lam L, Woo J (2008) Vitamin B-12 supplementation did not improve cognition but reduced delirium in demented patients with vitamin B-12 deficiency. Arch Gerontol Geriatr 46:273–282

    CAS  Google Scholar 

  125. Kwok T, Lee J, Law CB, Pan PC, Yung CY (2011) A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr 30:297–302

    CAS  Google Scholar 

  126. van Uffelen J, Chinapaw M, van Mechelen W, Hopman-Rock M (2008) Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med 42:344

    Google Scholar 

  127. de Jager C, Oulhaj A, Jacoby R, Refsum H, Smith AD (2012) Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 27:592–600

    Google Scholar 

  128. Durga J, van Boxtel M, Schouten E, Kok F, Jolles J, Katan M (2007) Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 369:208–216

    CAS  Google Scholar 

  129. Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H (2012) Oral folic acid and vitamin B12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms-the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 95:194–203

    Google Scholar 

  130. Eussen S, de Groot L, Joosten L, Bloo R, Clarke R, Ueland P (2006) Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr 84:361–370

    CAS  Google Scholar 

  131. Kwok T, Tang C, Woo J, Lai W, Law L, Pang C (1998) Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Int J Geriatr Psychiatry 13:611–616

    CAS  Google Scholar 

  132. Brady C, Gaziano J, Cxypoliski R, Guarino P, Kaufman J, Warren S (2009) Homocysteine lowering and cognition in CKD: the Veterans affairs Homocysteine Study. Am J Kidney Dis 54:440–449

    CAS  Google Scholar 

  133. Lewerin C, Matousek M, Steen G, Johansson B, Steen B, Nilsson-Ehle H (2005) 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 81:1155–1162

    CAS  Google Scholar 

  134. McMahon J, Green T, Skeaff C, Knight R, Mann J, Williams S (2006) A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 354:2764–2772

    CAS  Google Scholar 

  135. Pathansali R, Mangoni A, Creagh-Brown B, Lan Z, Ngow G, Yuan X (2006) Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr 43:127–137

    CAS  Google Scholar 

  136. Stott D, MacIntosh G, Lowe GD, Rumley A, McMahon A, Langhorne P (2005) Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr 82:1320–1326

    CAS  Google Scholar 

  137. Hvas A, Juul S, Lauritzen L, Nexo E, Ellegaard J (2004) No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord 81:269–273

    CAS  Google Scholar 

  138. Kang J, Cook N, Manson J, Buring J, Albert C, Grodstein F (2008) A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 88:1602–1610

    CAS  Google Scholar 

  139. Food and Nutrition Board, Institute of Medicine, National Academies (1998) Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academy Press, Washington

    Google Scholar 

  140. Smith A, Smith S, de Jager C, Whitbread P, Johnston C, Agacinski G (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE 5:e12244

    Google Scholar 

  141. Viswanathan A, Raj S, Greenberg S, Stampfer M, Campbell S, Hyman B (2009) Plasma A beta, homocysteine, and cognition The Vitamin Intervention for Stroke Prevention (VISP) trial. Neurology 72:268–272

    CAS  Google Scholar 

  142. Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S (2005) S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 28:195–204

    CAS  Google Scholar 

  143. Fuso A, Nicolia V, Pasqualato A, Fiorenza MT, Cavallaro RA, Scarpa S (2011) Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency. Neurobiol Aging 32:187–199

    CAS  Google Scholar 

  144. Zhuo J, Pratico D (2010) Acceleration of brain amyloidosis in an Alzheimer’s disease mouse model by a folate, vitamin B6 and B12-deficient diet. Exp Gerontol 45:195–201

    CAS  Google Scholar 

  145. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155

    CAS  Google Scholar 

  146. Huang T, Yuan G, Zhang Z, Zou Z, Li D (2008) Cardiovascular pathogenesis in hyperhomocysteinemia. Asia Pac J Clin Nutr 17:8–16

    Google Scholar 

  147. Rajagopalan P, Hua X, Toga A, Jack C, Weiner M (2011) Homocysteine effects on brain volumes mapped in 732 elderly individuals. NeuroReport 22:391–395

    CAS  Google Scholar 

  148. den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MMB (2003) Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 126:170–175

    Google Scholar 

  149. Homocysteine Lowering Trialists′ Collaboration (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82:806–812

    Google Scholar 

  150. Verhaar MC, Stroes E, Rabelink TJ (2002) Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 22:6–13

    CAS  Google Scholar 

  151. Scheltens P, Twisk WR, Blesa R, Scarpini E, von Arnim AF, Bongers A, Harrison J, Swinkels SHN, de Waal H, Wurtman RJ, Wieggers RL, Vellas B, Kamphuis PJGH (2012) Efficacy of souvenaid in Mild Alzheimer’s disease: results from a randomized, controlled trial. J Alz Dis 31:225–236

    CAS  Google Scholar 

  152. Scheltens P, Kamphuis P, Verhey F, Rikker M, Wurtman R, Wilkinson D (2010) Efficacy of a medical food in mild Alzheimer’s disease: a randomized, controlled trial. Alzheimer’s Dement 6:1–10

    CAS  Google Scholar 

  153. Shah R, Kamphuis P, Leurgans S, Swinkels S, Sadowsky C, Bongers A, Rappaport S, Quinn J, Wieggers R, Bennett D, Scheltens P (2011) Souvenaid as an add-on intervention in patients with mild to moderate Alzheimer’s disease using Alzheimer’s disease medication: results from a randomized, controlled, double-blind study (S-Connect). J Nutr Health Aging 15(Suppl):1

    Google Scholar 

  154. Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB (2010) A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. J Nutr Health Aging 14:224–230

    CAS  Google Scholar 

  155. Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB (2009) Efficacy of a vitamin/nutraceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Am J Alzheimer’s Dis Other Demen 23:571–585

    Google Scholar 

  156. Remington R, Chan A, Paskavitz J, Shea T (2009) Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a Placebo-controlled pilot study. Am J Alzheimer’s Dis Other Demen 24:27–33

    Google Scholar 

  157. Sun Y, Lu C, Chien K, Chen S, Chen R (2007) Efficacy of multivitamin supplementation containing vitamins B-6 and B-12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer’s disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther 29:2204–2214

    CAS  Google Scholar 

  158. Wolters M, Hickstein M, Flintermann A, Tewes U, Hahn A (2005) Cognitive performance in relation to vitamin status in healthy elderly German women-the effect of 6-month multivitamin supplementation. Prev Med 41:253–259

    Google Scholar 

  159. Gustaw-Rothenberg K (2009) Dietary patterns associated with Alzheimer’s disease: population based study. Int J Environ Res Publ Health 6:1335–1340

    Google Scholar 

  160. Gu Y, Nieves J, Stern Y, Luchsinger J, Scarmeas N (2010) Food combination and Alzheimer disease risk a protective diet. Arch Neurol 67:699–706

    Google Scholar 

  161. Hughes T, Andel R, Small B, Borenstein A, Mortimer J, Wolk A (2010) Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins. Am J Geriatr Psychiatry 18:413–420

    Google Scholar 

  162. Barberger-Gateau P, Lambert JC, Féart C, Pérés K, Ritchie K, Dartigues JF, Alpérovitch A (2013) From genetics to dietetics: the contribution of epidemiology to understanding Alzheimer’s disease. J Alz Dis 33:S457–S463

    Google Scholar 

  163. Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D (1995) Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 61:S1402–S1406

    Google Scholar 

  164. Gardener S, Gu Y, Rainey-Smith SR, Keogh JB, Clifton PM, Mathieson SL, Taddel K, Mondal A, Ward VK, Scarmeas N, Barnes M, Ellis KA, Head R, Masters CL, Ames D, Macaulay SL, Rowe CC, Szoeke C, Martins RN, the AIBL Research Group (2012) Adherence to a Mediterranean diet and Alzheimer’s disease risk in Australian population. Transl Psychiatry 2:e164

  165. Scarmeas N, Stern Y, Tang M, Mayeux R, Luchsinger J (2006) Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 59:912–921

    Google Scholar 

  166. Scarmeas N, Stern Y, Mayeux R, Luchsinger J (2006) Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol 63:1709–1717

    Google Scholar 

  167. Scarmeas N, Stern Y, Mayeux R, Manly J, Schupf N, Luchsinger J (2009) Mediterranean diet and mild cognitive impairment. Arch Neurol 66:216–225

    Google Scholar 

  168. Scarmeas N, Luchsinger J, Schupf N, Brickman A, Cosentino S, Tang M (2009) Physical activity, diet, and risk of Alzheimer disease. JAMA 302:627–637

    CAS  Google Scholar 

  169. Féart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues J (2009) Adherence to a mediterranean diet, cognitive decline, and risk of dementia. JAMA 302:638–648

    Google Scholar 

  170. Gu Y, Luchsinger JA, Stern Y, Scarmeas N (2010) Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. J Alz Dis 22:483–492

    CAS  Google Scholar 

  171. Roberts RO, Geda YE, Cerhan JR, Knopman DS, Cha RH, Christianson TJH, Pankratz VS, Ivnik RJ, Boeve BF, O′Connor HM, Petersen RC (2010) Vegetables, unsaturated fats, moderate alcohol intake, and mild cognitive impairment. Dement Geriatr Cogn Disord 29:413–423

    CAS  Google Scholar 

  172. Cherbuin N, Anstey KJ (2012) The Mediterranean diet is not related to cognitive change in a large prospective investigation: the PATH through life study. Am J Geriatr Psychiatry 20:635–639

    Google Scholar 

  173. Psaltopoulou T, Kyrozis A, Stathopoulos P, Trichopoulos D, Vassilopoulos D, Trichopoulou A (2008) Diet, physical activity and cognitive impairment among elders: the EPIC-Greece cohort (European Prospective Investigation in Cancer and Nutrition). Public Health Nutr 11:1054–1062

    CAS  Google Scholar 

  174. Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC (2011) Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr 93:601–607

    CAS  Google Scholar 

  175. Vercambre MN, Grodstein F, Berr C, Kang JH (2012) Mediterranean diet and cognitive decline in women with cardiovascular disease or risk factors. J Acad Nutr Diet 112:816–823

    Google Scholar 

  176. Samieri C, Okereke OI, Devore EE, Grodstein F (2013) Long-term adherence to the Mediterranean diet is associated with overall cognitive status, but not cognitive decline, in women. J Nutr 143:493–499

    CAS  Google Scholar 

  177. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P, Polychronopoulos E, Vassilakou T, Lipworth L, Trichopoulos D (1995) Diet and overall survival in elderly people. BMJ 311:1457–1460

    CAS  Google Scholar 

  178. Trichopoulou A, Costacou T, Barnia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348:2599–2608

    Google Scholar 

  179. Munoz M, Fito M, Marrugat J, Covas M, Schroder H (2009) Adherence to the Mediterranean diet is associated with better mental and physical health. Br J Nutr 101:1821–1827

    CAS  Google Scholar 

  180. Féart C, Pérès K, Samieri C, Letenneur L, Dartigues J, Barberger-Gateau P (2011) Adherence to a Mediterranean diet and onset of disability in older persons. Eur J Epidemiol 26:747–756

    Google Scholar 

  181. Buckland G, Agudo A, Travier N, Maria Huerta J, Cirera L, Huerta J, Tormo M, Navarro C, Chirlaque M, Moreno Iribas C, Ardanaz E, Barricarte A, Etxeberria J, Marin P, Quirás JR, Redondo M, Larrañaga N, Amiano P, Dorronsoro M, Arriola L, Basterretxea M, Sanchez M, Molina E, González C (2011) Adherence to the Mediterranean diet reduces mortality in the Spanish cohort of the European prospective investigation into cancer and nutrition (EPIC-Spain). Br J Nutr 106:1581–1591

    CAS  Google Scholar 

  182. Estruch R, Ros E, Salas-Salvadó J, Covas M, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos R, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA (2013) Primary prevention of cardiovascular disease with a mediterranean diet. N Engl J Med 368:1279–1290

    Google Scholar 

  183. Misirli G, Benetou V, Lagiou P, Bamia C, Trichopoulos D, Trichopoulou A (2012) Relation of the traditional Mediterranean diet to cerebrovascular disease in a Mediterranean population. Am J Epidemiol 176:1185–1192

    Google Scholar 

  184. Nordmann AJ, Suter-Zimmermann K, Bucher HC, Shai I, Tuttle KR, Estruch R, Briel M (2011) Meta-analysis comparing mediterranean to low-fat diets for modification of cardiovascular risk factors. Am J Med 124:841–851

    Google Scholar 

  185. Gardener H, Scarmeas N, Gu Y, Boden Albala B (2012) Mediterranean diet and white matter hyperintensity volume in the Northern Manhattan study. Arch Neurol 69:251–256

    Google Scholar 

  186. Scarmeas N, Luchsinger JA, Stern Y, Gu Y, He J, DeCarli C, Brown T, Brickman AM (2011) Mediterranean diet and magnetic resonance imaging-assessed cerebrovascular disease. Ann Neurol 69:257–268

    Google Scholar 

  187. Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, Solfrizzi V (2010) Nutraceutical properties of mediterranean diet and cognitive decline: possible underlying mechanisms. J Alz Dis 22:715–740

    CAS  Google Scholar 

  188. Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (2011) Midlife healthy-diet index and late-life dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord Extra 1:103–112

    Google Scholar 

  189. Smith P, Blumenthal J, Babyak M, Craighead L, Welsh Bohmer K, Browndyke J, Strauman T, Sherwood A (2010) Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension 55:1331–1338

    CAS  Google Scholar 

  190. Kesse-Guyot E, Amieva H, Castetbon K, Henegar A, Ferry M, Jeandel C, Hercberg S, Galan P, the SU.VI.MAX 2 Research Group (2011) Adherence to nutritional recommendations and subsequent cognitive performance: findings from the prospective Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2) study. Am J Clin Nutr 93:200–210

    Google Scholar 

  191. Wengreen H, Neilson C, Munger R, Corcoran C (2009) Diet quality is associated with better cognitive test performance among aging men and women. J Nutr 139:1944–1949

    CAS  Google Scholar 

  192. Shatenstein B, Ferland G, Belleville S, Gray-Donald K, Kergoat M, Morais J, Gaudreau P, Payette H, Greenwood C (2012) Diet quality and cognition among older adults from the NuAge study. Exp Gerontol 47:353–360

    Google Scholar 

  193. Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, Kaye JA, Shannon J, Quinn JF (2012) Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 78:241–249

    CAS  Google Scholar 

  194. Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson GS, Bonner LM, Callaghan M, Leverenz JB, Walter BK, Tsai E, Plymate SR, Postupna N, Wilkinson CW, Zhang J, Lampe J, Kahn SE, Craft S (2011) Diet intervention and cerebropinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol 68:743–752

    Google Scholar 

  195. Belkacemi A, Doggui S, Dao L, Ramassamy C (2011) Challenges associated with curcumin therapy in Alzheimer disease. Expert Rev Mol Med 13:e34

    Google Scholar 

  196. Chandra V, Ganguli M, Pandav R, Johnston J, Belle S, DeKosky ST (1998) Prevalence of Alzheimer’s disease and other dementias in rural India. Neurology 51:1000–1008

    CAS  Google Scholar 

  197. Vas CJ, Pinto C, Panikker D, Noronha S, Deshpande N, Kulkarni L, Sachdeva S (2001) Prevalence of dementia in an urban Indian population. Int Psychogeriatr 13:439–450

    CAS  Google Scholar 

  198. Wang H, Zhao Y, Zhang S, Liu G, Kang W, Tang H, Ding J, Chen S (2010) PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes. J Alz Dis 20:1189–1199

    CAS  Google Scholar 

  199. Bateman R, Xiong C, Fagan A, Goate A (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367:795–804

    CAS  Google Scholar 

  200. Fajardo V, Alonso Aperte E, Varela Moreiras G (2012) Lack of data on folate in convenience foods: should ready-to-eat products be considered relevant for folate intake? The European challenge. J Food Comp Anal 28:155–163

    CAS  Google Scholar 

  201. Harris K, Fleming J, Kris-Etherton P (2011) Challenges in estimating omega-3 fatty acid content of seafood from US nutrient database: a salmon case study. J Food Comp Anal 24:1168–1173

    CAS  Google Scholar 

  202. Mazzeo T, N′Dri D, Chiavaro E, Visconti A, Fogliano V, Pellegrini N (2011) Effect of two cooking procedures on phytochemical compounds, total antioxidant capacity and colour of selected frozen vegetables. Food Chem 128:627–633

    Google Scholar 

  203. Delchier N, Reich M, Renard CMGC (2012) Impact of cooking methods on folates, ascorbic acid and lutein in green beans (Phaseolus Vulgaris) and spinach (Spinacea Oleracea). LWT Food Sci Technol 49:197–201

    CAS  Google Scholar 

  204. Ansorena D, Guembe A, Mendizábal T, Astiasarán I (2010) Effect of fish and oil nature on frying process and nutritional product quality. J Food Sci 75:H62–H67

    CAS  Google Scholar 

  205. Larsen D, Quek SY, Eyres L (2010) Effect of cooking method on the fatty acid profile of New Zealand King Salmon (Oncorhynchus Tshawytscha). Food Chem 119:785–790

    CAS  Google Scholar 

  206. Stephen NM, Shakila JR, Jeyasekaran G, Sukumar D (2010) Effect of different types of heat processing on chemical changes in tuna. J Food Sci Tech 47:174–181

    CAS  Google Scholar 

Download references

Acknowledgments

Authors thank to the researchers of Fundación CITA-alzhéimer Fundazioa for their expert advice. A predoctoral fellowship grant (Programa Predoctoral, de Formación de Personal Investigador no doctor, RBFI-2012-90) was received from the Basque Government (AOA).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, Fundación CITA-alzhéimer Fundazioa, Paseo Mikeletegi 71, Planta 1, 20009, San Sebastián, Guipúzcoa, Spain

    Ane Otaegui-Arrazola & Pablo Martínez-Lage

  2. Public Health Division of Gipuzkoa, Research Institute of BioDonostia, Basque Government, San Serbastián, Spain

    Pilar Amiano

  3. CIBER, CIBER of Epidemiology and Public Health, Madrid, Spain

    Pilar Amiano

  4. Department of Nutrition and Health, University of the Basque Country, San Sebastián, Spain

    Ana Elbusto

  5. Basque Culinary Center, San Sebastián, Spain

    Elena Urdaneta

  6. CIBERNED, CIBER of Neurodegenerative diseases, San Sebastián, Spain

    Pablo Martínez-Lage

Authors
  1. Ane Otaegui-Arrazola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pilar Amiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Elbusto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Urdaneta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pablo Martínez-Lage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ane Otaegui-Arrazola.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Otaegui-Arrazola, A., Amiano, P., Elbusto, A. et al. Diet, cognition, and Alzheimer’s disease: food for thought. Eur J Nutr 53, 1–23 (2014). https://doi.org/10.1007/s00394-013-0561-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-013-0561-3

Keywords

Search

Navigation