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Cognitive and Emotional Health Project: The Healthy Brain

Dietary Factors


Vitamin B12 deficiency is known to cause cognitive impairment and dementia in elderly individuals. Whether less severe variations in vitamin B intake contribute to variations in cognitive function in well-nourished populations is unclear. In prospective observational studies, elevated blood levels of homocysteine have been associated with an increased risk of cardiovascular disease, as well as Alzheimer's disease and other forms of dementia, although the findings have not been consistent. Supplementation with B vitamins, including folic acid, vitamin B6, and vitamin B12, is an effective method for reducing homocysteine levels and may thus help prevent cardiovascular disease, cognitive decline, and dementia. B vitamins may also prevent these conditions by additional mechanisms other than lowering homocysteine. Large-scale prevention trials of vitamin B supplementation are lacking, however.

Calvaresi E, Bryan J. B vitamins, cognition, and aging: a review. J Gerontol B Psychol Sci Soc Sci 2001;56: P327-39.

Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hofman A, Breteler MM. Total homocysteine and cognitive decline in a community-based sample of elderly subjects:     the Rotterdam Study. Am J Epidemiol 1999;150:283-9

Malouf R, Grimley EJ. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003;4:CD004393.

Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev 2003;3:CD004326.

Mattson MP. Gene-diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med 2003;139:441-4.

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.

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.

Riggs KM, Spiro A, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate and homocysteine to cognitive performance in the Normative Aging Study. Am J     Clin Nutr 1996;63:306-314.

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.

Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr 2000;71:614S-620S.

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.


Antioxidant vitamins such as vitamin E, vitamin C, and beta-carotene may be important in protecting the brain from oxidant injury. Many large prospective observational studies suggest that high intakes of, or high blood concentrations of, these antioxidants may help protect against cognitive decline or dementia. However, evidence from randomized clinical trials that antioxidants promote cognitive vitality or prevent dementia is lacking. Several relevant trials are ongoing, however, and should help resolve this question. It is worth noting that there is a divergence of findings from observational studies and randomized clinical trials on the role of vitamin E, the most intensively studied of the antioxidant vitamins in epidemiologic settings to date, in cardiovascular disease prevention. Although many prospective observational studies suggest that a high vitamin E intake may prevent cardiovascular disease, randomized trials have failed to find that vitamin E supplementation reduces the risk of future cardiovascular events in primary or secondary prevention settings.

Cotman CW. Homeostatic processes in brain aging: the role of apoptosis, inflammation, and oxidative stress in regulating healthy neural circuitry in the aging brain.     In: Stern PC, Carstensen LL (eds.) The Aging Mind: Opportunities in Cognitive Research. National Research Council, Commission on Behavioral and Social     Sciences and Education. Washington DC: National Academy Press, 2000.

Englehart MJ, Geerlings MI, Ruitenberg A, van Sweiten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease.     JAMA 2002;287:3223-9.

Grodstein F, Chen J, Willett WC. High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Am J Clin Nutr 2003;77:975-84.

Haan MN. Can vitamin supplements prevent cognitive decline and dementia in old age? Am J Clin Nutr 2003;77:762-3.

Jama JW, Launer LJ, Witteman JC, den Breeijen JH, Breteler MM, Grobbee DE, Hofman A. Dietary antioxidants and cognitive function in a population-based sample     of older persons: The Rotterdam Study. Am J Epidemiol 1996;144:275-280.

Launer LJ, Kalmijn S. Anti-oxidants and cognitive function: A review of clinical and epidemiologic studies. J Neural Transmission Suppl 1998;53:1-8.

Martin A, Cherubini A, Andres-Lacueva C, Paniagua M, Joseph J. Effects of fruits and vegetables on levels of vitamins E and C in the brain and their association with     cognitive function. J Nutr Health Aging 2002;6:392-404.

Martin A, Youdim K, Szprengiel A, Shukitt-Hale B, Joseph J. Roles of vitamins E and C on neurodegenerative diseases and cognitive performance. Nutr Rev      2002;60:308-26.

Masaki KH, Losonczy MA, Izmirlian G, Foley MS, Ross GW, Petrovich H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive     function and dementia in elderly men. Neurology 2000;54:1265-72.

Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS. Vitamin E and cognitive decline in older persons. Arch Neurol 2002;59:1125-32.

Morris MC, Beckett LA, Scherr PA, Hebert E, Bennett DA, Field TS, Evans DA. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.     Alzheimer Disease & Associated Disorders 1998;12:121-6.

Paleologos M, Cumming RG, Lazarus R. Cohort study of vitamin C intake and cognitive impairment. Am J Epidemiol 1998;148:45-50.

Peacock JM, Folsom AR, Knopman DS, Mosley TH, Goff DC Jr, Szklo M. Dietary antioxidant intake and cognitive performance in middle-aged adults. The     Atherosclerosis Risk in Communities (ARIC) Study investigators. Public Health Nutrition 2000;3:337-43.

Perkins AJ, Hendrie HC, Callahan CM, Gao S, Unverzagt FW, Xu Y, Hall KS, Hui SL. Association of antioxidants with memory in a multiethnic elderly sample using     the Third National Health and Nutrition Examination Survey. Am J Epidemiol 1999;150:37-44.

Perrig WJ, Perrig P, Stahelin HB. The relationship between antioxidants and memory performance in the old and very old. J Am Geriatr Soc 1997;45:718-24.

Schmidt R, Hayn R, Fazekas F, Kapeller P, Esterbauer H. Magnetic resonance imaging white matter hyperintensities in clinically normal elderly individuals:     Correlations with plasma concentrations of naturally occurring antioxidants. Stroke 1996;27:2043-2047.

Schmidt R, Hayn M, Reinhart B, Roob G, Schmidt H, Schumacher M, Watzinger N, Launer LJ. Plasma antioxidants and cognitive performance in middle-aged and     older adults: Results of the Austrian Stroke Prevention Study. J Am Geriatr Soc 1998;46:1407-10

Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of     selignine, alpha-tocopherol, or both as a treatment for Alzheimer's disease. N Engl J Med 1997;336:1216-1222.

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC. Reduced risk of Alzheimer disease in     users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004;61:82-88.


Essential fatty acids include the long-chain omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). The main omega-3 fatty acid is alpha-linolenic acid (ALA), found in certain plant oils, and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in fish. The main omega-6 fatty acid is linoleic acid (LA). Laboratory, epidemiologic, and intervention studies suggest that the ratio of omega-6 to omega-3 fatty acids may affect cardiovascular and cognitive health. This ratio is approximately 20:1 in the typical U.S. diet; however, the optimal ratio is thought to lie somewhere between 1:1 and 4:1. For most Americans, this means greatly reducing the omega-6 fatty acids they consume, and increasing the number of omega-3 fatty acids. Though sparse, data from large-scale epidemiologic studies suggest that PUFA intake may play a role in preventing cognitive dysfunction or dementia.

Haag M. Essential fatty acids and the brain. Can J Psychiatry 2003; 48:195-203.175

Kalmijn S. Fatty acid intake and the risk of dementia and cognitive decline: a review of clinical and epidemiological studies. J Nutr Health Aging 2000; 4:202-7.176


Prospective observational studies suggest that light-to-moderate alcohol use may prevent cognitive decline and dementia.

Galanis DJ, Joseph C, Masaki KH, Petrovitch H, Ross GW, White L. A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study. Am J Public Health 2000; 90:1254-9.177

Hebert LE, Scherr PA, Beckett LA, Albert MS, Rosner B, Taylor JO, Evans DA. Relation of smoking and low-to-moderate alcohol consumption to change in cognitive function: a longitudinal study in a defined community of older persons. Am J Epidemiol 1993; 137:881-91.80

Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. J Clin Epidemiol 2002; 55:959-64.178

Kalmijn S, van Boxtel MP, Verschuren MW, Jolles J, Launer LJ. Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age. Am J Epidemiol 2002; 156:936-44.81

Leroi I, Sheppard JM, Lyketsos CG. Cognitive function after 11.5 years of alcohol use: relation to alcohol use. Am J Epidemiol 2002;156:747-52.179

Letenneur L, Larrieu S, Barberger-Gateau P. Alcohol and tobacco consumption as risk factors of dementia: a review of epidemiological studies. Biomed Pharmacother. 2004;58:95-99. 82

Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, Hofman A, Breteler MM. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 2002; 359:281-6.180

Truelsen T, Thudium D, Gronbaek M. Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurology 2002; 59:1313-9.181