title: Diet, cognition, and Alzheimer's disease: food for thought.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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".
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Fundación CITA-alzhéimer Fundazioa, Paseo Mikeletegi 71, Planta 1, 20009, San Sebastián, Guipúzcoa, Spain, aotaegui@cita-alzheimer.org.
authors.forename: Ane
authors.initials: A
authors.lastname: Otaegui-Arrazola
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.forename: Ana
authors.initials: A
authors.lastname: Elbusto
authors.forename: Elena
authors.initials: E
authors.lastname: Urdaneta
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Lage
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000517:prevention & control; D000975:Antioxidants / Q000008:administration & dosage; D003071:Cognition; D004032:Diet; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D006801:Humans; D015201:Meta-Analysis as Topic; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D014803:Vitamin B Complex
references.citation: Neurology. 2005 Apr 12;64(7):1152-6
references.pmid: 15824339
references.citation: Eur J Neurol. 2009 Sep;16 Suppl 1:1-7
references.pmid: 19703213
references.citation: BMJ. 1995 Dec 2;311(7018):1457-60
references.pmid: 8520331
references.citation: Alzheimers Dement. 2005 Jul;1(1):11-8
references.pmid: 19595811
references.citation: Arch Neurol. 2010 Jul;67(7):819-25
references.pmid: 20625087
references.citation: J Geriatr Psychiatry Neurol. 2003 Sep;16(3):156-9
references.pmid: 12967058
references.citation: Am J Epidemiol. 1996 Aug 1;144(3):275-80
references.pmid: 8686696
references.citation: N Engl J Med. 2005 Jun 9;352(23):2379-88
references.pmid: 15829527
references.citation: Am J Clin Nutr. 2006 Aug;84(2):361-70
references.pmid: 16895884
references.citation: Arch Gerontol Geriatr. 2008 May-Jun;46(3):273-82
references.pmid: 17561285
references.citation: Neurology. 2004 Jan 27;62(2):275-80
references.pmid: 14745067
references.citation: N Engl J Med. 1997 Apr 24;336(17):1216-22
references.pmid: 9110909
references.citation: Neurology. 1998 Oct;51(4):1000-8
references.pmid: 9781520
references.citation: Neuroreport. 2011 Jun 11;22(8):391-5
references.pmid: 21512418
references.citation: Arch Neurol. 2007 Jan;64(1):86-92
references.pmid: 17210813
references.citation: J Nutr. 2002 Jul;132(7):2065-8
references.pmid: 12097694
references.citation: N Engl J Med. 2003 Jun 26;348(26):2599-608
references.pmid: 12826634
references.citation: Int Psychogeriatr. 2001 Dec;13(4):439-50
references.pmid: 12003250
references.citation: Am J Clin Nutr. 2008 Feb;87(2):449-54
references.pmid: 18258638
references.citation: Am J Alzheimers Dis Other Demen. 2009 Feb-Mar;24(1):27-33
references.pmid: 19056706
references.citation: Am J Clin Nutr. 2007 Apr;85(4):1142-7
references.pmid: 17413117
references.citation: J Nutr. 2002 Jun;132(6):1345-56
references.pmid: 12042457
references.citation: Am J Med. 2006 Sep;119(9):751-9
references.pmid: 16945610
references.citation: Alzheimers Dement. 2012;8(2):131-68
references.pmid: 22404854
references.citation: Neuropharmacology. 2010 Sep-Oct;59(4-5):290-4
references.pmid: 20394761
references.citation: JAMA. 1997 Mar 12;277(10):813-7
references.pmid: 9052711
references.citation: Brain. 2003 Jan;126(Pt 1):170-5
references.pmid: 12477704
references.citation: Arch Gerontol Geriatr. 2006 Jul-Aug;43(1):127-37
references.pmid: 16359741
references.citation: Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):6-13
references.pmid: 11788454
references.citation: BMJ. 2002 Oct 26;325(7370):932-3
references.pmid: 12399342
references.citation: Am J Clin Nutr. 2009 Jul;90(1):170-6
references.pmid: 19474131
references.citation: J Biol Chem. 2011 Apr 22;286(16):14028-39
references.pmid: 21324907
references.citation: Clin Ther. 2007 Oct;29(10):2204-14
references.pmid: 18042476
references.citation: JAMA. 2002 Jun 26;287(24):3223-9
references.pmid: 12076218
references.citation: Neurobiol Aging. 2006 Nov;27(11):1694-704
references.pmid: 16256248
references.citation: Arch Neurol. 2009 Feb;66(2):216-25
references.pmid: 19204158
references.citation: J Nutr Health Aging. 2010 Mar;14(3):224-30
references.pmid: 20191258
references.citation: Neurology. 2000 Mar 28;54(6):1265-72
references.pmid: 10746596
references.citation: Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600
references.pmid: 21780182
references.citation: Age Ageing. 2004 Jan;33(1):34-41
references.pmid: 14695861
references.citation: Arch Neurol. 2005 Apr;62(4):641-5
references.pmid: 15824266
references.citation: Am J Clin Nutr. 2003 Apr;77(4):803-8
references.pmid: 12663275
references.citation: Neurology. 2012 Jun 5;78(23):1832-40
references.pmid: 22551728
references.citation: J Alzheimers Dis. 2009;17(1):143-9
references.pmid: 19494439
references.citation: Lancet Neurol. 2004 Oct;3(10):579-87
references.pmid: 15380154
references.citation: Alzheimers Dement. 2010 Nov;6(6):456-64
references.pmid: 20434961
references.citation: J Alzheimers Dis. 2010;20(4):1189-99
references.pmid: 20413894
references.citation: Am J Clin Nutr. 2005 Feb;81(2):508-14
references.pmid: 15699242
references.citation: Am J Clin Nutr. 2003 Apr;77(4):975-84
references.pmid: 12663300
references.citation: Int J Environ Res Public Health. 2009 Apr;6(4):1335-40
references.pmid: 19440521
references.citation: Public Health Nutr. 2010 Sep;13(9):1403-9
references.pmid: 20059796
references.citation: Am J Clin Nutr. 2010 Jun;91(6):1725-32
references.pmid: 20410089
references.citation: J Alzheimers Dis. 2012;31(1):225-36
references.pmid: 22766770
references.citation: Chem Phys Lipids. 2004 Nov;132(1):79-88
references.pmid: 15530450
references.citation: Nutr Res. 2012 May;32(5):390-4
references.pmid: 22652379
references.citation: Arch Neurol. 2011 Jun;68(6):743-52
references.pmid: 21670398
references.citation: Am J Clin Nutr. 2005 Dec;82(6):1320-6
references.pmid: 16332666
references.citation: Arch Neurol. 2006 Nov;63(11):1545-50
references.pmid: 17101822
references.citation: Neurosci Lett. 2006 Apr 24;397(3):170-3
references.pmid: 16413966
references.citation: Dement Geriatr Cogn Disord. 2010;29(5):413-23
references.pmid: 20502015
references.citation: Am J Clin Nutr. 2011 Mar;93(3):601-7
references.pmid: 21177796
references.citation: J Neurochem. 2002 Jun;81(5):1084-91
references.pmid: 12065621
references.citation: Arch Neurol. 2010 Jun;67(6):699-706
references.pmid: 20385883
references.citation: Am J Clin Nutr. 2005 May;81(5):1155-62
references.pmid: 15883442
references.citation: Prev Med. 2005 Jul;41(1):253-9
references.pmid: 15917019
references.citation: Neurology. 2001 May 8;56(9):1188-94
references.pmid: 11342684
references.citation: Am J Med. 2011 Sep;124(9):841-51.e2
references.pmid: 21854893
references.citation: Neurology. 2005 Nov 8;65(9):1409-14
references.pmid: 16275829
references.citation: J Affect Disord. 2004 Sep;81(3):269-73
references.pmid: 15337331
references.citation: Arch Neurol. 2002 Jun;59(6):972-6
references.pmid: 12056933
references.citation: J Alzheimers Dis. 2010;22(3):715-40
references.pmid: 20858954
references.citation: Am J Clin Nutr. 2011 Jan;93(1):200-10
references.pmid: 21106918
references.citation: Clin Nutr. 2011 Jun;30(3):297-302
references.pmid: 21216507
references.citation: JAMA. 2007 Feb 28;297(8):842-57
references.pmid: 17327526
references.citation: Neurology. 2007 Nov 13;69(20):1921-30
references.pmid: 17998483
references.citation: JAMA. 2002 Jun 26;287(24):3230-7
references.pmid: 12076219
references.citation: Br J Nutr. 2012 Jun;107 Suppl 2:S137-51
references.pmid: 22591888
references.citation: Br J Nutr. 2009 Jun;101(12):1821-7
references.pmid: 19079848
references.citation: Cochrane Database Syst Rev. 2012 Mar 14;(3):CD007176
references.pmid: 22419320
references.citation: Mol Cell Neurosci. 2005 Jan;28(1):195-204
references.pmid: 15607954
references.citation: Int J Geriatr Psychiatry. 1998 Sep;13(9):611-6
references.pmid: 9777425
references.citation: Neurology. 2012 Feb 28;78(9):658-64
references.pmid: 22371413
references.citation: Neurobiol Aging. 2005 Dec;26 Suppl 1:98-102
references.pmid: 16226347
references.citation: JAMA. 2008 Oct 15;300(15):1774-83
references.pmid: 18854539
references.citation: PLoS One. 2010 Sep 08;5(9):e12244
references.pmid: 20838622
references.citation: Am J Clin Nutr. 2008 Dec;88(6):1602-10
references.pmid: 19064521
references.citation: JAMA. 2009 Aug 12;302(6):627-37
references.pmid: 19671904
references.citation: Br J Nutr. 2009 Aug;102(3):419-27
references.pmid: 19203415
references.citation: Exp Gerontol. 2006 Jun;41(6):619-27
references.pmid: 16697546
references.citation: N Engl J Med. 2013 Apr 4;368(14):1279-90
references.pmid: 23432189
references.citation: Am J Clin Nutr. 2007 Apr;85(4):1103-11
references.pmid: 17413112
references.citation: Lipids. 2000 Dec;35(12):1305-12
references.pmid: 11201991
references.citation: Dement Geriatr Cogn Disord. 2006;22(1):99-107
references.pmid: 16710090
references.citation: Curr Aging Sci. 2011 Jul;4(2):158-70
references.pmid: 21235492
references.citation: J Acad Nutr Diet. 2012 Jun;112(6):816-23
references.pmid: 22709809
references.citation: J Alzheimers Dis. 2010;21(4):1165-77
references.pmid: 21504121
references.citation: Asia Pac J Clin Nutr. 2008;17(1):8-16
references.pmid: 18364320
references.citation: J Am Coll Cardiol. 2011 Nov 8;58(20):2047-67
references.pmid: 22051327
references.citation: Br J Nutr. 2003 Apr;89(4):483-9
references.pmid: 12654166
references.citation: Exp Gerontol. 2010 Mar;45(3):195-201
references.pmid: 20005283
references.citation: Am J Clin Nutr. 2007 Feb;85(2):511-7
references.pmid: 17284751
references.citation: J Alzheimers Dis. 2006 Aug;9(4):435-43
references.pmid: 16917153
references.citation: Arch Intern Med. 2006 Dec 11-25;166(22):2462-8
references.pmid: 17159011
references.citation: Public Health Nutr. 2008 Oct;11(10):1054-62
references.pmid: 18205988
references.citation: Lancet. 2007 Jan 20;369(9557):208-16
references.pmid: 17240287
references.citation: Eur J Epidemiol. 2011 Sep;26(9):747-56
references.pmid: 21874560
references.citation: J Alzheimers Dis. 2013;33 Suppl 1:S457-63
references.pmid: 22683527
references.citation: Neurology. 2004 May 11;62(9):1573-9
references.pmid: 15136684
references.citation: JAMA. 2011 Apr 6;305(13):1348-9
references.pmid: 21467288
references.citation: J Nutr. 2013 Apr;143(4):493-9
references.pmid: 23365105
references.citation: Eur J Epidemiol. 2000 Apr;16(4):357-63
references.pmid: 10959944
references.citation: J Alzheimers Dis. 2003 Aug;5(4):315-22
references.pmid: 14624027
references.citation: Dement Geriatr Cogn Dis Extra. 2011 Jan;1(1):103-12
references.pmid: 22163237
references.citation: Am J Clin Nutr. 2002 May;75(5):908-13
references.pmid: 11976166
references.citation: Ann Neurol. 2006 Jun;59(6):912-21
references.pmid: 16622828
references.citation: Am J Clin Nutr. 2004 Jul;80(1):114-22
references.pmid: 15213037
references.citation: Arch Neurol. 2003 Jul;60(7):940-6
references.pmid: 12873849
references.citation: J Alzheimers Dis. 2010;22(2):483-92
references.pmid: 20847399
references.citation: Br J Nutr. 2011 Nov;106(10):1581-91
references.pmid: 21736834
references.citation: J Nutr. 2009 Oct;139(10):1944-9
references.pmid: 19675102
references.citation: Am J Med. 2005 Feb;118(2):161-7
references.pmid: 15694902
references.citation: Neurosci Res. 2006 Oct;56(2):159-64
references.pmid: 16905216
references.citation: Arch Neurol. 2006 Oct;63(10):1402-8
references.pmid: 17030655
references.citation: N Engl J Med. 1991 Apr 25;324(17):1149-55
references.pmid: 2011158
references.citation: Arch Neurol. 2012 Jul;69(7):836-41
references.pmid: 22431837
references.citation: Neurosci Lett. 2007 Jun 29;421(3):209-12
references.pmid: 17574755
references.citation: N Engl J Med. 2012 Aug 30;367(9):795-804
references.pmid: 22784036
references.citation: Arch Neurol. 2003 Feb;60(2):203-8
references.pmid: 12580704
references.citation: Crit Rev Food Sci Nutr. 2008 Sep;48(8):760-74
references.pmid: 18756398
references.citation: J Lipid Res. 2001 Aug;42(8):1257-65
references.pmid: 11483627
references.citation: Am J Clin Nutr. 1995 Jun;61(6 Suppl):1402S-1406S
references.pmid: 7754995
references.citation: Clin Interv Aging. 2010 Nov 02;5:313-6
references.pmid: 21103402
references.citation: Psychopharmacology (Berl). 2013 Feb;225(3):605-12
references.pmid: 22932777
references.citation: Am J Geriatr Psychiatry. 2012 Jul;20(7):635-9
references.pmid: 21937919
references.citation: Hypertension. 2010 Jun;55(6):1331-8
references.pmid: 20305128
references.citation: Neurobiol Aging. 2006 Feb;27(2):262-9
references.pmid: 16399211
references.citation: JAMA. 2010 Nov 3;304(17):1903-11
references.pmid: 21045096
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2013 Jan;88(1):127-9
references.pmid: 23022417
references.citation: Lancet. 2003 Jun 14;361(9374):2017-23
references.pmid: 12814711
references.citation: Dement Geriatr Cogn Disord. 2009;28(6):536-40
references.pmid: 20016184
references.citation: Neurology. 2010 Oct 19;75(16):1408-14
references.pmid: 20956786
references.citation: J Food Sci Technol. 2010 Mar;47(2):174-81
references.pmid: 23572621
references.citation: Am J Clin Nutr. 2009 Jul;90(1):184-92
references.pmid: 19474137
references.citation: Front Aging Neurosci. 2010 Feb 09;2:3
references.pmid: 20552043
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44
references.pmid: 18573585
references.citation: Am J Epidemiol. 2004 May 15;159(10):959-67
references.pmid: 15128608
references.citation: Int J Geriatr Psychiatry. 2008 Jul;23(7):741-7
references.pmid: 18188871
references.citation: J Neurochem. 2009 Oct;111(2):568-79
references.pmid: 19686246
references.citation: Clin Interv Aging. 2010 Apr 07;5:45-61
references.pmid: 20396634
references.citation: Transl Psychiatry. 2012 Oct 02;2:e164
references.pmid: 23032941
references.citation: Ann Intern Med. 2005 Jan 4;142(1):37-46
references.pmid: 15537682
references.citation: Neurology. 2012 Jan 24;78(4):241-9
references.pmid: 22205763
references.citation: Am J Alzheimers Dis Other Demen. 2008 Dec-2009 Jan;23(6):571-85
references.pmid: 19047474
references.citation: Br J Sports Med. 2008 May;42(5):344-51
references.pmid: 18308888
references.citation: Alzheimers Dement. 2011 Jan;7(1):61-73
references.pmid: 21255744
references.citation: Neurobiol Aging. 2011 Feb;32(2):187-99
references.pmid: 19329227
references.citation: Am J Kidney Dis. 2009 Sep;54(3):440-9
references.pmid: 19628319
references.citation: J Neurochem. 2008 Dec;107(6):1634-46
references.pmid: 19014387
references.citation: Arch Neurol. 2012 Feb;69(2):251-6
references.pmid: 22332193
references.citation: Ann Neurol. 2011 Feb;69(2):257-68
references.pmid: 21387371
references.citation: Arch Neurol. 1998 Nov;55(11):1449-55
references.pmid: 9823829
references.citation: Am J Clin Nutr. 2011 Jul;94(1):278-86
references.pmid: 21593490
references.citation: Ann Pharmacother. 2005 Dec;39(12):2009-14
references.pmid: 16227448
references.citation: N Engl J Med. 2006 Jun 29;354(26):2764-72
references.pmid: 16807413
references.citation: J Food Sci. 2010 Mar;75(2):H62-7
references.pmid: 20492236
references.citation: Alzheimers Dement. 2010 Jan;6(1):1-10.e1
references.pmid: 20129316
references.citation: Br J Nutr. 2010 Mar;103(5):730-4
references.pmid: 20028599
references.citation: Am J Clin Nutr. 2007 Sep;86(3):728-34
references.pmid: 17823439
references.citation: Int J Biochem Cell Biol. 1998 Feb;30(2):197-207
references.pmid: 9608673
references.citation: Am J Geriatr Psychiatry. 2010 May;18(5):413-20
references.pmid: 19910881
references.citation: J Alzheimers Dis. 2011;27(4):909-22
references.pmid: 21891867
references.citation: Arch Neurol. 2005 Dec;62(12):1849-53
references.pmid: 16216930
references.citation: J Nutr Health Aging. 2009 Dec;13(10):899-905
references.pmid: 19924351
references.citation: Am J Clin Nutr. 2005 Sep;82(3):636-43
references.pmid: 16155278
references.citation: Arch Neurol. 2004 Jan;61(1):82-8
references.pmid: 14732624
references.citation: Arch Intern Med. 2007 Nov 12;167(20):2184-90
references.pmid: 17998490
references.citation: J Neurosci. 2005 Mar 23;25(12):3032-40
references.pmid: 15788759
references.citation: JAMA. 2009 Aug 12;302(6):638-48
references.pmid: 19671905
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2004 Nov;71(5):341-6
references.pmid: 15380822
references.citation: Am J Clin Nutr. 2012 Jan;95(1):194-203
references.pmid: 22170358
references.citation: Brain Behav Immun. 2012 Aug;26(6):988-95
references.pmid: 22640930
references.citation: Expert Rev Mol Med. 2011 Nov 04;13:e34
references.pmid: 22051121
references.citation: Neurochem Res. 2012 Dec;37(12):2706-14
references.pmid: 22878647
references.citation: Circulation. 2009 Jun 2;119(21):2772-80
references.pmid: 19451353
references.citation: Am J Clin Nutr. 2005 Sep;82(3):627-35
references.pmid: 16155277
references.citation: Int J Geriatr Psychiatry. 2001 Jun;16(6):609-14
references.pmid: 11424170
references.citation: Am J Clin Nutr. 2005 Oct;82(4):806-12
references.pmid: 16210710
references.citation: Arch Neurol. 2006 Dec;63(12):1709-17
references.pmid: 17030648
references.citation: Exp Gerontol. 2012 May;47(5):353-60
references.pmid: 22386581
references.citation: J Neuropathol Exp Neurol. 2000 Nov;59(11):1011-7
references.pmid: 11089579
references.citation: J Neurosci. 2001 Jun 15;21(12):4183-7
references.pmid: 11404403
references.citation: Neurology. 2012 Aug 14;79(7):642-50
references.pmid: 22855869
references.citation: Br J Nutr. 2012 Apr;107(8):1119-27
references.pmid: 21899800
references.citation: Am J Epidemiol. 2007 Jun 15;165(12):1364-71
references.pmid: 17369607
references.citation: Neurology. 2008 Aug 5;71(6):430-8
references.pmid: 18678826
references.citation: Am J Epidemiol. 2012 Dec 15;176(12):1185-92
references.pmid: 23186748
references.citation: Neurology. 2009 Jan 20;72(3):268-72
references.pmid: 19153374