The American Journal of Medicine
Volume 123, Issue 6 , Pages 522-527.e2 , June 2010

Effect of Folic Acid, with or without Other B Vitamins, on Cognitive Decline: Meta-Analysis of Randomized Trials

References 

  1. Crook T, Bartus RT, Ferris SH, et al. for the National Institute of Mental Health Work Group (Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change). Dev Neuropsychol. 1986;2:261–276
  2. Levy R. Aging-associated cognitive decline. Int Psychogeriatr. 1994;6:63–68
  3. Hanninen T, Hallikainen M, Koivisto K, et al. A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia. J Am Geriatr Soc. 1995;43:1007–1015
  4. Peterson RC, Doody R, Kurz A, et al. Current concepts in mild cognitive development. Arch Neurol. 2001;58:1985–1992
  5. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by Cobalamin deficiency in the absence of anaemia or macrocytosis. N Engl J Med. 1988;318:1720–1728
  6. Bell IR, Edman JS, Selhub J, et al. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand. 1992;86:386–390
  7. 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
  8. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Discord. 1999;10:12–20
  9. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2001;73:927–933
  10. McCaddon A, Davies G, Hudson P, et al. Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry. 1998;13:235–239
  11. Fioravanti M, Ferrario E, Massaia M, et al. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch Gerontol Geriatr. 1997;26:1–13
  12. Eussen SJ, de Groot LC, Joosten LW, et al. 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. 2006;84:361–370
  13. McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of Homocysteine lowering and cognitive performance. N Engl J Med. 2006;354:2764–2772
  14. Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369:208–216
  15. Balk EM, Raman G, Tatsioni A, et al. Vitamin B6, B12 and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med. 2007;167:21–30
  16. Bryan J, Calvaresi E, Hughes D. 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. 2002;132:1345–1356
  17. Lewerin C, Matousek M, Steen G, et al. 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. 2005;81:1155–1162
  18. Pathansali R, Mangoni AACreagh-Brown, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr. 2006;43:127–137
  19. Stott DJ, MacIntosh G, Lowe GDO, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82:1320–1326
  20. McNeill G, Avenell A, Campbell MK, et al. Effect of multivitamin and multi-mineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial. Nutr J. 2007;6:10
  21. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  22. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558
  23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634
  24. Malouf R, Grimley Evans J, Areosa Sastre A. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;(4):CD004514
  25. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr. 2000;71:993–998
  26. Dawe B, Procter A, Philpot M. Concepts of mild memory impairment in the elderly and their relationship to dementia: a review. Int J Geriatr Psychiatry. 1992;7:473–479
  27. Richards M, Touchon J, Ledesert B, Richie K. Cognitive decline in aging: are AAMI and AACD distinct entities?. Int J Geriatr Psychiatr. 1999;14:534–540
  28. Lane F, Snowdon J. A longitudinal survey of suburban elderly. In:  Lovibond P,  Wilson P editor. Clinical and Abnormal Psychology. Amsterdam, The Netherlands: Elsevier; 1989;p. 365–376
  29. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet. 2006;367:1262–1270
  30. Lovden M, Bergman L, Adolfsson R, et al. Studying individual aging in an international context: typical pathos of age-related, dementia-related, and mortality-related cognitive development in old age. Psych Aging. 2005;20:303–316
  31. Visser PJ, Verhey FR, Ponds RW, Jolles J. Diagnosis of preclinical Alzheimer's disease in a clinical setting. Int Psychogeriatr. 2001;13:411–423
  32. VITAL Trial Collaborative Group. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Int Med. 2003;254:67–75
  33. Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300:1774–1783
  34. Mason JB, Dickstein A, Jacques PF, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16:1325–1329
  35. Charles D, Ness AR, Campbell D, et al. Taking folate in pregnancy and risk of maternal breast cancer. BMJ. 2004;329:1375–1376
  36. Bayston R, Russell A, Wald NJ, Hoffbrand AV. Folic acid fortification and cancer risk. Lancet. 2007;370:2004
  37. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007;297:2351–2359
  38. Folic acid: an update on scientific developments. EFSA Meeting Summary Report, 2009. http://www.efsa.europa.eu/en/scpublications/publication/efsafolicacid.pdfAccessed April 19, 2010
  39. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369:1876–1882

 Funding: None.

 Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.

 Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(10)00131-2

doi: 10.1016/j.amjmed.2010.01.017

The American Journal of Medicine
Volume 123, Issue 6 , Pages 522-527.e2 , June 2010