Ageing International

, Volume 29, Issue 1, pp 28–45 | Cite as

Mechanisms and evidence for the role of nutrition in cognitive ageing

Public Forum Papers Invited Paper


This review examines the mechanisms and empirical evidence from epidemiological and experimental studies for the role of the B vitamins folate and vitamins B-12 and B-6, antioxidants, omega 3 polyunsaturated fatty acids (PUFAs) and the popular herbal supplement, Ginkgo biloba in the maintenance and enhancement of cognitive performance in older adults. Although there are plausible mechanisms by which these dietary components could affect cognition, these hypothesized effects are yet to be clearly substantiated. As the effects of dietary components on cognitive performance are likely to be subtle, methodological issues such as appropriate outcome measures and adequate sample sizes need careful consideration.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, J.D., Klaidman, L.K., Odunze, I.N., Shen, H.C., & Miller, C.A. (1991). Alzheimer’s and Parkinson’s disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Molecular & Chemical Neuropathology, 14, 213–226.CrossRefGoogle Scholar
  2. Alpert, J.E. & Fava, M. (1997). Nutrition and depression: The role of folate. Nutrition Reviews, 55, 145–149.CrossRefGoogle Scholar
  3. Beaubrun, G., & Gray, G.E. (2000). A review of herbal medicines for psychiatric disorders. Psychiatric Services, 51, 1130–1134.CrossRefGoogle Scholar
  4. Bell, I.R., Edman, J.S., Marby, D.W., Satlin, A., Dreier, T., Liptzin, B., & Cole, J.O. (1990). Vitamin B12 and folate status in acute geropsychiatric inpatients: Affective and cognitive characteristics of a vitamin nondeficient population. Biological Psychiatry, 27, 125–137.CrossRefGoogle Scholar
  5. Bellisle, F., Blundell, J.E., Dye, L., Fantino, M., Fern, E., Fletcher, R.J., Lambert, J., Roberfroid, M., Specter, S., Westenhofer, J., & Westerterp-Plantenga, M.S. (1998). Functional food science and behaviour and psychological functions. British Journal of Nutrition, 80, S173-S193.CrossRefGoogle Scholar
  6. Berr, C., Richard, M.J., Roussel, A.M., & Bonithon-Kopp, C. (1998). Systemic oxidative stress and cognitive performance in the population-based EVA study. Free Radical Biological Medicine, 24, 1202–1208.CrossRefGoogle Scholar
  7. Birks, J., Grimley Evans, J., & van Dongen, M. (2002). Ginkgo biloba for cognitive impairment and dementia (Cochrane Review). In The Cochrane Library, Issue 4. Oxford: Update Software.Google Scholar
  8. Bottiglieri, T. (1996). Folate, vitamin B12, and neuropsychiatric disorders. Nutrition Reviews, 5, 382–390.Google Scholar
  9. Bottiglieri, T., Crellin, R.F., & Reynolds, E.H. (1995). Folate and neuropsychiatry. In K.B. Bailey (Ed.) Folate in health and disease. New York: Marcel Dekker. pp. 435–462.Google Scholar
  10. Bruinsma, K.A. & Taren, D.L. (2000). Dieting, essential fatty acid intake, and depression. Nutrition Reviews, 58, 98–108.CrossRefGoogle Scholar
  11. Bryan, J. (1998). Cognitive function and its links with nutrition. Proceedings of the Nutritional Society of Australia, 22, 211–215.Google Scholar
  12. Bryan, J., & Calvaresi, E. (2003). Associations between dietary intake of folate and vitamins B-12 and B-6 and self-reported cognitive function and psychological well-being in Australian men and women in midlife. Journal of Nutrition, Health and Aging.Google Scholar
  13. Bryan, J., Calvaresi, E., & Hughes, D. (2002). Short-term folate, B-12 and B-6 supplementation slightly affect memory performance but not mood in women of various ages. Journal of Nutrition, 132, 1345–1356.Google Scholar
  14. Calvaresi, E. & Bryan, J. (2001). B vitamins, cognition and ageing: A review. Journal of Gerontology: Psychological Sciences, 56, P327-P339.Google Scholar
  15. Carmel, R., Gott, P.S., & Waters, C.H. (1995). The frequently low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities. European Journal of Haematology, 54, 245–253.CrossRefGoogle Scholar
  16. Carney, J.M., Starke-Reed, P.E., Oliver, C.N., Landum, R.W., Cheng, M.S., Wu, J.F., & Floyd, R.A. (1991). Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-ert-butyl-a-phenylnitrone. Proceedings of the National Academy of Science USA, 88, 3633–3636.CrossRefGoogle Scholar
  17. Cassarino, D.S. & Bennett, J.P. (1999). An evaluation of the role of mitochondria in neurodegenerative diseases: Mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death neurodegeneration. Brain Research Review, 29, 1–25.CrossRefGoogle Scholar
  18. Clark, R., Smith, A.D., Jobst, K.A., Refsum, H., Sutton, L., & Ueland, P.M. (1998). Folate, vitamin B12 and serum total homocysteine levels in confirmed Alzheimer disease. Archives of Neurology, 55, 1449–1455.CrossRefGoogle Scholar
  19. Crystal, H.A., Ortof, E., & Frishman, W.H. (1994). Serum vitamin B 12 levels and incidence of dementia in a health elderly population: a report from the Bronx longitudinal aging study. Journal of the American Geriatric Society, 42, 933–936.Google Scholar
  20. Curtis-Prior, P., Vere, D., & Fray, P. (1999). Therapeutic value of Ginkgo biloba in reducing symptoms of decline in mental function. Journal of Pharmacy and Pharmacology, 51, 535–541.CrossRefGoogle Scholar
  21. Deijen, J.B., van der Beek, E.J., Orlebeke, J.F., & van den Berg, H. (1992). Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology, 109, 489–496.CrossRefGoogle Scholar
  22. Delion, S., Chalon, S., Hearault, J., Guilloteau, D., Besnard, J.C., & Durannd, G. (1994). Chronic dietary-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. Journal of Nutrition, 124, 2466–2476.Google Scholar
  23. Ebly, E.M., Schaefer, J.P., Campbell, N.R.C., & Hogan, D.B. (1998). Folate status, vascular disease and cognition in elderly Canadians. Age & Ageing, 27, 485–491.Google Scholar
  24. Endres, S., Ghorbani, R., Kelley, V.E., Georgilis, K., Lonnemann, G., van der Meer, J.W.M., Cannon, J.G., Rogers, T.S., Klempner, M.S., Weber, P.C., Schaefer, E.J., Wolfe, S.M., & Dinarello. (1989). The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. New England Journal of Medicine, 320, 265–271.CrossRefGoogle Scholar
  25. Fenech, M., Aitken, C., & Rinaldi, J. (1998). Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis, 19, 1163–1171.CrossRefGoogle Scholar
  26. Fioravanti, M., Ferrario, E., Massaia, M., Cappa, G., Rivolta, G., Grossi, E., & Buckley, A.E. (1997). Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Archives of Gerontology & Geriatrics, 26, 1–13.CrossRefGoogle Scholar
  27. Fontanari, D., Di Plama, C., Giorgetti, F., Violante, F., & Voltolina, M. (1994). Effects of S-Adenosyl-l-methionine on cognitive and vigilance functions in the elderly. Current Therapeutic Research, 55, 682–689.CrossRefGoogle Scholar
  28. Goodwin, J.S., Goodwin, J.M., & Garry, P.J. (1983). Association between nutritional status and cognitive functioning in a healthy elderly population. Journal of the American Medical Association, 249, 2917–2921.CrossRefGoogle Scholar
  29. Grunwald, J. (1995). The European phytomedicines: market figures, trends, analyses. Herbalgram, 34, 60–65.Google Scholar
  30. Hankey, G.J. & Eikelboom, J.W. (1999). Homocysteine and vascular disease. Lancet, 354, 407–413.CrossRefGoogle Scholar
  31. Hassing, L., Wahlin, A., Winblad, D., & Bäckman, L. (1999). Further Evidence on the effects of vitamin B12 and folate levels on episodic memory functioning: A population-based study on healthy very old adults. Biological Psychiatry, 45, 1472–1480.CrossRefGoogle Scholar
  32. Ikeda, T., Furukawa, Y., Mashimoto, S., Takahashi, K., & Yamada, M. (1990). Vitamin B 12 levels in serum and cerebrospinal fluid of people with Alzheimer’s disease. Acta Psychiatric Scandanavia, 82, 327–329.Google Scholar
  33. Jama, J.W., Launer, L.J., Witteman, J.C.M., Breeijen, J.H., Grobbee, D.E., & Hofman, A. (1996). Dietary antioxidants and cognitive function in a population-based sample of older persons. American Journal of Epidemiology, 144, 275–280.Google Scholar
  34. Joosten, E., van den Berg, A., Riezler, R., Naurath, J.J., Lindenbaum, J., Stabler, S.P., & Allen, R.H. (1993). Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate and vitamin B-6 occur commonly in elderly people. American Journal of Clinical Nutrition, 58, 468–476.Google Scholar
  35. Kalmijn, S., Feskens, E.J.M., Launer, L.J., & Kromhout, D. (1997). Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. American Journal of Epidemiology, 145, 145; 33–41.Google Scholar
  36. Karnaze, D.S. & Carmel, R. (1987). Low serum cobalamin levels in primary degenerative dementia. Archives of International Medicine, 147, 429–431.CrossRefGoogle Scholar
  37. Kinsella, J.E., Lokesh, B., & Stone, R.A. (1990). Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: Possible mechanisms. American Journal of Clinical Nutrition, 52, 1–28.Google Scholar
  38. Knopman, D.S., De Kosky, S.T., Cummings, J.L., Chui, H., Corey-Bloom, J., Relkin, N., Small, G.W., Miller, B., & Stevens, J.C. (2001). Practice parameter: Diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 1143–1153.Google Scholar
  39. La Rue, A., Koehler, K.M., Wayne, S.J., Chiulli, S.J., Haaland, K.Y., & Garry, P.J. (1997). Nutritional status and cognitive functioning in a normally aging sample: A 6-year reassessment. American Journal of Clinical Nutrition, 65, 20–29.Google Scholar
  40. Le Bars, P.L., Katz, M.M., Berman, N., Itil, T.M., Freedman, A.M., & Schatzberg, A.M. (1997). A placebo-controlled, double-blind randomised trial of an extract of Ginkgo biloba for dementia. Journal of the American Medical Association, 278, 1327–1332.CrossRefGoogle Scholar
  41. Lethem, R. & Orrell, M. (1997). Antioxidants and dementia. Lancet, 349, 1189–1190.CrossRefGoogle Scholar
  42. Levitt, A.J. & Karlinsky, H. (1992). Folate, vitamin B 12 and cognitive impairment in patients with Alzheimer’s disease. Acta Psychiatrica Scandanavia, 86, 301–305.Google Scholar
  43. Lim, S.Y. & Suzuki, H. (2000). Intakes of dietary docosahexaenoic acid ethyl ester and egg phophatidylcholine improve maze-learning ability in young and old mice. Journal of Nutrition, 130, 1629–1632.Google Scholar
  44. Lindeman, R.D., Romero, L.J., Koehler, K.M., Liang, H.C., LaRue, A., Baumgartner, R.N., & Garry, P.J. (2000). Serum vitamin B12, C and folate concentrations in the New Mexico Elder Health Survey: Correlations with cognitive and affective functions. Journal of the American College of Nutrition, 19, 68–76.Google Scholar
  45. Martin, D.C., Francis, J., Protetch, J., & Huff, F.J. (1992). Time dependency of cognitive recovery with cobalamin replacement: Report of a pilot study. Journal of the American Gerontological Society, 40, 168–172.Google Scholar
  46. Mazza, G. (1998). Functional foods: Biochemical and processing aspects. Lancaster PA: Technomic.Google Scholar
  47. McCaddon, A., Davies, G., Hudson, P., Tandy, S., & Cattell, H. (1998). Total serum homocysteine in senile dementia of Alzheimer type. International Journal of Geriatric Psychiatry, 13, 235–239.CrossRefGoogle Scholar
  48. Mendelsohn, A.B., Belle, S.H., Stoeher, G.P., & Ganguli, M. (1998). Use of antioxidant supplements and its association with cognitive function in a rural elderly cohort. American Journal of Epidemiology, 148, 38–44.Google Scholar
  49. Mix, J.A., & Crews, W.D. (2000). An examination of the efficacy of Ginkgo biloba extract EGb 761 on the neuropsychological functioning of cognitively intact older adults. The Journal of Alternative and Complimentary Medicine, 6, 219–229.Google Scholar
  50. Nilsson, K., Gustafson, L., Faldt, R., Andersson, A., & Hultberg, B. (1994). Plasma homocysteine in relation to serum cobalamin and blood folate in a psychogeriatric population. European Journal of Clinical Investigation, 24, 600–606.CrossRefGoogle Scholar
  51. Nourhashémi, F., Gillet-Guyonnet, S., Andrieu, S., Ghisolfi, A., Ousset, P.J., Grandjean, H., Grand, A., Pous, J., Vellas, B., & Albarede, J.L. (2000). Alzheimer’s disease: protective factors. American Journal of Clinical Nutrition, 71, 643S-649S.Google Scholar
  52. O’Donnell, E. & Lynch, M.A. (1998). Dietary antioxidant supplementation reverses age-related neuronal changes. Neurobiology & Aging, 19, 461–467.CrossRefGoogle Scholar
  53. Oken, B.S., Storzbach, D.M., & Kaye, J.A. (1998). The efficacy of Ginkgo biloba on cognitive function in Alzheimer’s disease. Archives of Neurology, 35, 1409–1415.CrossRefGoogle Scholar
  54. Ortega, R.M., Manas, L.R., Andres, P., Gaspar, M.J., Agudo, R.R., Jiminez, A., & Pascual, T. (1996). Functional and psychic deterioration in elderly people may be aggravated by folate deficiency. Journal of Nutrition, 126, 1192–1199.Google Scholar
  55. Ortega, R.M., Requejo, A.M., Andres, P., Lopez-Sobaler, A.M., Quintas, M.E., Redondo, M.R., Navaia, B., & Rivas, T. (1997). Dietary intake and cognitive function in a group of elderly people. American Journal of Clinical Nutrition, 66, 803–809.Google Scholar
  56. Paleogos, M., Cumming, R.G., & Lazarus, R. (1998). Cohort study of vitamin C intake and cognitive impairment. American Journal of Epidemiology, 148, 45–50.Google Scholar
  57. Perkins, A.J., Hendrie, H.C., Callahan, C.M., Gao, S., Unverzagt, F.W., Xu, Y., Hall, K.S., & Hui, S.L. (1999). Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey. American Journal of Epidemiology, 150, 37–44.Google Scholar
  58. Perrig, W.J., Perrig, P., & Stahelin, H.B. (1997). The relation between antioxidants and memory performance in the old and very old. Journal of the American Geriatrics Society, 45, 718–724.Google Scholar
  59. Piccini, C., Bracco, L., & Amaducci, L. (1998). Treatable and reversible dementias: and update. Journal of Neurological Science, 153, 172–181.CrossRefGoogle Scholar
  60. Ramassamy, C., Christen, Y., Clostre, F., & Costentin, J. (1992). The Ginkgo biloba extract, EGb 761, increases synaptosomal uptake of 5-hydroxytryptamine: in vitro and ex-vivo studies. Journal of Pharmacy and Pharmacology, 44, 943–945.Google Scholar
  61. Riedel, W.J. & Jorissen, B.L. (1998). Nutrients, age and cognitive function. Current Opinions in Clinical Nutrition and Metabolic Care, 1, 579–586.CrossRefGoogle Scholar
  62. Riggs, K.M., Spiro, A., Tucker, K., & Rush, D. (1996). Relations of vitamin B-12, folate, and homocysteine to cognitive performance in the Normative Aging Study. American Journal of Clinical Nutrition, 63, 306–314.Google Scholar
  63. Rogers, J. & Bloom, F.E. (1995). Neurotransmitter metabolism and function in the aging nervous system. In C.E. Finch & E.L. Schneider (Eds.). Handbook of the Biology of Ageing. New York: Van Nostrand Reinhold. pp. 645–691.Google Scholar
  64. Rosenberg, I.H. & Miller, J.W. (1995). Nutritional factors in physical and cognitive functions of elderly people. American Journal of Clinical Nutrition, 55, 1237S-1243S.Google Scholar
  65. Rundle, B. (2000). The effect of vitamin B-12 and folate on cognitive performance and psychological well-being. Unpublished Honours thesis. University of Adelaide.Google Scholar
  66. Salthouse TA. (1991). Theoretical perspectives on cognitive aging. Hillsdale, NJ: Erlbaum.Google Scholar
  67. Sano, M., Ernesto, C., & Thomas, R.G. (1997). A controlled trial of selegiline, alpha-tocopherol, or both as a treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. New England Journal of Medicine, 336, 1216–1222.CrossRefGoogle Scholar
  68. Sauberlich, H.E. (1991). Relationship of vitamin B-6, vitamin B-12, and folate to neurological and neuropsychiatric disorders. In A. Bendich & C.E. Butterworth (Eds.) Micronutrients in health and in disease prevention. New York: Marcel Dekker. pp. 187–218.Google Scholar
  69. Selhub, J., Bagley, L.C., Miller, J., & Rosenberg, I.H. (2000). B vitamins, homocysteine, and neurocognitive function in the elderly. American Journal of Clinical Nutrition, 71, 614S-620S.Google Scholar
  70. Selhub, J., Jacques, P.F., Bostom, A.G., D’Agostino, R.N., Wilson, P.W.F., Belanger, A.J., O’Leary, D.H., Wolf, P.A., Schaefer, E.J., & Rosenberg, I.H. (1995). Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. New England Journal of Medicine, 331, 286–291.CrossRefGoogle Scholar
  71. Sneath, P., Chanarin, I., Hodkinson, H.M., McPherson, C.K., & Reynolds, E.H. (1973). Folate status in a geriatric population and its relation to dementia. Age & Ageing, 2, 177–182.CrossRefGoogle Scholar
  72. Snowdon, D.A., Tully, C.L., Smith, C.D., Riley, K.P., & Markesbery, W.R. (2000). Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: Findings from the Nun Study. American Journal of Clinical Nutrition, 71, 993–998.Google Scholar
  73. Söderberg, M., Edlund, C., Kristensson, K., & Dallner G. (1991). Fatty acid composition of brain phospholipids in aging and Alzheimer’s disease. Lipids, 26, 421–425.CrossRefGoogle Scholar
  74. Solomon, P.R., Adams, F., Silver, A., Zimmer, J., & DeVeaux, R. (2002). Ginkgo for memory enhancement. A randomized controlled trial. Journal of the American Medical Association, 288, 835–840.CrossRefGoogle Scholar
  75. Sommer, B.R. & Wolkowitz, O.M. (1988). RBC folic acid levels and cognitive performance in elderly patients: a preliminary report. Biological Psychiatry, 24, 352–354.CrossRefGoogle Scholar
  76. Stoll, A.L., Locke, C.A., Marangell, L.B., & Severus, W.E. (1999). Omega-3 fatty acids and bipolar disorder: A review. Prostaglandins, Leukotrines & Essential Fatty Acids, 60, 329–337.CrossRefGoogle Scholar
  77. Teunisse, A.E.B., von Gool, W.A., & Walstra, G.J.M. (1996). Dementia and subnormal levels of vitamin B 12: effects of replacement therapy on dementia. Journal of Neurology, 243, 522–529.CrossRefGoogle Scholar
  78. Tolonen, M., Schrijver, J., Westermarck, T., Halme, M., Touminen, S.E.J., Frilander, A., Keinonen, M., & Sarna, S. (1988). Vitamin B-6 status of Finnish elderly. Comparison with Dutch younger adults and elderly. The effect of supplementation. International Journal of Vitamin & Nutrition Research, 58, 73–77.Google Scholar
  79. Ueland, P.M. & Refsum, H. (1989) Plasma homocysteine, a risk factor for vascular disease: Plasma levels in health, disease, and drug therapy. Journal of Laboratory Clinical Medicine, 114, 473–499.Google Scholar
  80. van Dongen, M.J.M., van Rossum, E., Kessels, A.G.H., Sielhorst, H.J.G., & Knipschild, P.G. (2000). The efficacy of Ginkgo for elderly people with dementia and age-associated memory impairment: New results of a randomized clinical trial. JAGS, 48, 1183–1194.Google Scholar
  81. Vesper, J., & Hänsgen, K.D. (1994). Efficacy of Ginkgo biloba in 90 outpatients with cerebral insufficiency caused by old age. Phytomedicine, 1, 9–16.Google Scholar
  82. Wahlin, A., Hill, R.D., Winblad, B., & Bäckman, L. (1996). Effects of serum vitamin B12 and folate status on episodic memory performance in very old age: A population based study. Psychology & Aging, 11, 487–496.CrossRefGoogle Scholar
  83. Wainwright, P.E., Xing, H.C., Girard, T., Parker, L., & Ward, G.R. (1998). Effects of dietary (n-3) fatty acid deficiency on Morris water-maze performance and amphetamine-induced conditioned place preference in rats. Nutritional Neuroscience, 1, 281–293.Google Scholar
  84. Wirth, S., Stemmelin, J., Will, B., Christen, Y., & Di Scala, G. (2000). Facilitative effects of EGb 761 on olfactory recognition in young and aged rats. Pharmacology Biochemistry and Behavior, 65, 321–326.CrossRefGoogle Scholar
  85. Witztum, J.L. (1994). The oxidation hypothesis of atherosclerosis. Lancet, 244, 793–795.CrossRefGoogle Scholar
  86. Zaman, Z., Roche, S., Fielden, P., Frost, P.G., Niriella, D.C., & Cayley, A.C. (1992). Plasma concentrations of vitamins A and E and carotenoids in Alzheimer’s disease. Age & Aging, 21, 91–94.CrossRefGoogle Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  1. 1.Centre for Applied Psychological ResearchUniversity of South AustraliaAdelaideAustralia

Personalised recommendations