Intake of flavonoids and risk of dementia


It has been postulated that oxidative stress may play a key role in dementia. This is substantiated by the recent discovery of the protective effect of wine. In wine, the flavonoids – powerful antioxidant substances also contained in tea, fruits and vegetables – have been thought to offer such protection. We investigated whether flavonoid intake could be associated with a lower incidence of dementia in a cohort of 1367 subjects above 65 years of age (Paquid). A questionnaire was used to evaluate their intake of flavonoids and subjects were followed-up for 5 years between 1991 and 1996: 66 incident cases of dementia were observed. We estimated the relative risk (RR) of dementia according to tertiles of flavonoid intake using a Cox model. The age-adjusted RR of dementia was 0.55 for the two highest tertiles compared to the lowest (95% CI: 0.34–0.90; p = 0.02). After additional adjustment for gender, education, weight and vitamin C intake, the RR was 0.49 (95% CI: 0.26–0.92; p = 0.04). We conclude that the intake of antioxidant flavonoids is inversely related to the risk of incident dementia.

This is a preview of subscription content, access via your institution.


  1. 1.

    Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of a apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921–923.

    PubMed  Google Scholar 

  2. 2.

    Ji Y, Urakami K, Adachi Y, et al. Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease. Dement Geriatr Cogn Disord 1998; 9: 243–245.

    PubMed  Google Scholar 

  3. 3.

    Stengard JH, Weiss KM, Sing CF. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum Genet 1998; 103: 234–241.

    PubMed  Google Scholar 

  4. 4.

    Kalmijn S, Feskens EJ, Launer LJ, et al. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 1997; 145: 33–41.

    PubMed  Google Scholar 

  5. 5.

    Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997; 42: 776–782.

    PubMed  Google Scholar 

  6. 6.

    St Leger AS, Cochrane AL, Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet 1979; 1(8124): 1017–1020.

    PubMed  Google Scholar 

  7. 7.

    Orgogozo JM, Dartigues JF, Lafont S, et al. Wine consumption and dementia in the elderly: A prospective community study in the Bordeaux area. Rev Neurol 1997; 153: 185–192.

    PubMed  Google Scholar 

  8. 8.

    Lemeshow S, Letenneur L, Dartigues JF, et al. Illustration of analysis taking into account complex survey considerations: The association between wine consumption and dementia in the PAQUID study. Personnes Agees Quid.Am J Epidemiol 1998; 148: 298–306.

    Google Scholar 

  9. 9.

    Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 1997; 23: 134–147.

    PubMed  Google Scholar 

  10. 10.

    Steinberg D, Parthasarathy S, Carew T, et al. Modification of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989; 320: 915–924.

    PubMed  Google Scholar 

  11. 11.

    Ceballos-Picot I. The role of oxidative stress in neuronal death. Landes Bioscience, Springer, 1997. ISBN:1–57059–454–6.

  12. 12.

    Thome J, Gsell W, Rosler M, et al. Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease. Life Sci 1997; 60: 13–19.

    PubMed  Google Scholar 

  13. 13.

    Münch G, Schinzel R, Loske C, et al. Alzheimer's disease-synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm 1998; 105: 439–461.

    PubMed  Google Scholar 

  14. 14.

    Rösler M, Retz W, Thome J, Riederer P. Free radicals in Alzheimer's dementia: currently available therapeutic strategies. J Neural Transm Suppl 1998; 54: 211–219.

    PubMed  Google Scholar 

  15. 15.

    Ness AR, Powles JW. Fruit and vegetables, and car-diovascular disease: A review. Int J Epidemiol 1997; 26: 1–13.

    PubMed  Google Scholar 

  16. 16.

    Rimm EB, Ascherio A, Giovannucci E, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996; 275: 447–451.

    PubMed  Google Scholar 

  17. 17.

    Renaud SC, Ruf JC. Effects of alcohol on platelet functions. Clin Chim Acta 1996; 246: 77–89.

    PubMed  Google Scholar 

  18. 18.

    Serafini M, Maiani G, Ferro-Luzzi A. Alcohol-free red wine enhances plasma antioxidant capacity in humans. J Nutr 1998; 128: 1003–1007.

    PubMed  Google Scholar 

  19. 19.

    Miyagi Y, Miwa K, Inoue H. Inhibition of human low-density lipoprotein oxidation by flavonoids in red wine and grape juice. Am J Cardiol 1997; 80: 1627–1631.

    PubMed  Google Scholar 

  20. 20.

    Hertog MGL, Feskens EJM, Hollman PCH, et al. Dietary antioxidant flavonoids and risk of coronary heart disease: The Zutphen Elderly Study. Lancet 1993; 342: 1007–1011.

    PubMed  Google Scholar 

  21. 21.

    Dartigues JF, Gagnon M, Barberger-Gateau P, et al. The Paquid epidemiological program on brain ageing. Neuroepidemiol 1992; 11(suppl): S14–S18.

    Google Scholar 

  22. 22.

    American Psychiatric Association (1987) Diagnosis and statistical manual of mental disorders (3rd ed., revised) (DSM-III-R). Washington DC. ISBN:2–225–81602–6.

  23. 23.

    Folstein MF, Folstein SE, McHugh PR. Mini Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.

    PubMed  Google Scholar 

  24. 24.

    Hertog MGL, Hollman PCH, Venema DP. Optimization of quantitative HPLC determinant of potentially anticarcinogenic flavonoids in vegetables and fruits. J Agri Food Chem 1992; 40: 1591–1598.

    Google Scholar 

  25. 25.

    Hertog MGL, Hollman PCH, Katan MB. Content of potentially anticarcinogenic flavonoids of 28 vegatables and 9 fruits commonly consumed in the Netherlands. J Agri Food Chem 1992; 40: 2372–2383.

    Google Scholar 

  26. 26.

    Hertog MGL, Hollman PCH, Katan MB. Content of potentially anticarcinogenic flavonoids of tea infusions, wines and fruits juices. J Agri Food Chem 1993; 41: 1242–1246.

    Google Scholar 

  27. 27.

    Commenges D, Letenneur L, Joly P. Re: Serum transferrin saturation, stroke incidence, and mortality in women and men. The NHANES 1 epidemiologic follow-up study. Am J Epidemiol 1997; 146: 683–684 (letter).

    PubMed  Google Scholar 

  28. 28.

    Commenges D, Letenneur L, Jol P, et al. Modelling age-specific risk: Application to dementia. Stat Med 1998; 17: 1973–1988.

    PubMed  Google Scholar 

  29. 29.

    Letenneur L, Gilleron V, Commenges D, et al. Are gender and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the Paquid project. J Neurol Neurosurg Psychiatry 1999; 66: 177–183.

    PubMed  Google Scholar 

  30. 30.

    Hertog MG, Sweetnam PM, Fehily AM, et al. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: The Caerphilly Study. Am J Clin Nutr 1997; 65: 1489–1494.

    PubMed  Google Scholar 

  31. 31.

    Rimm EB, Katan MB, Ascherio A, et al. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 1996; 125: 384–389.

    PubMed  Google Scholar 

  32. 32.

    De Rijk MC, Breteler MM, Den Breeijen JH, et al. Dietary antioxidants and Parkinson disease. The Rotterdam Study. Arch Neurol 1997; 54: 762–765.

    PubMed  Google Scholar 

  33. 33.

    Jama JW, Launer LJ, Witteman JC, et al. Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam Study. Am J Epidemiol 1996; 144: 275–280.

    PubMed  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Commenges, D., Scotet, V., Renaud, S. et al. Intake of flavonoids and risk of dementia. Eur J Epidemiol 16, 357–363 (2000).

Download citation

  • Alzheimer's disease
  • Dementia
  • Flavonoids
  • Vitamin C