Skip to main content
Log in

Conversion from mild cognitive impairment to dementia: Influence of folic acid and vitamin B12 use in the vita cohort

  • Published:
The journal of nutrition, health & aging

Abstract

Objective

Increased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia.

Participants

A community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI.

Design

Prospective study with a retrospective evaluation of vitamin intake.

Measurements

Laboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up.

Results

The self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users.

Conclusions

These results from a middle european study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Sep;29:1152–1161.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Weir DG, Scott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull. 1999;55:669–682.

    Article  PubMed  CAS  Google Scholar 

  4. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA. 1983 Jun 3:249:2917–21.

    Google Scholar 

  5. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998 Nov;55:1449–1455.

    Article  PubMed  CAS  Google Scholar 

  6. Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008 Jun;29:S143–S172.

    PubMed  Google Scholar 

  7. Dangour AD, Whitehouse PJ, Rafferty K, Mitchell SA, Smith L, Hawkesworth S, Vellas B. B-vitamins and fatty acids in the prevention and treatment of Alzheimer’s disease and dementia: a systematic review. J Alzheimers Dis. 2010;22:205–224.

    PubMed  CAS  Google Scholar 

  8. Malouf R, Grimley EJ. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;CD004514.

  9. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5:el2244.

    Google Scholar 

  10. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2011 Jul 21.

  11. Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I, Tragi KH, Fischer P. Conversion from cognitive health to mild cognitive impairment and Alzheimer’s disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging. 2008 Jan;29:1–11.

    Article  PubMed  CAS  Google Scholar 

  12. Fischer P, Jungwirth S, Krampla W, Weissgram S, Kirchmeyr W, Schreiber W, Huber K, Rainer M, Bauer P, Tragi KH. Vienna Transdanube Aging “VITA”: study design, recruitment strategies and level of participation. J Neural Transm Suppl. 2002;105–116.

  13. Fischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, Krampla W, Tragi KH. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology. 2007 Jan 23:68:288–291.

    Article  PubMed  CAS  Google Scholar 

  14. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, et al. Mild cognitive impairment-beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004 Sep;256:240–246.

    Article  PubMed  CAS  Google Scholar 

  15. Jungwirth S, Weissgram S, Zehetmayer S, Tragi KH, Fischer P. VITA: subtypes of mild cognitive impairment in a community-based cohort at the age of 75 years. Int J Geriatr Psychiatry. 2005 May;20:452–458.

    Article  PubMed  CAS  Google Scholar 

  16. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology. 1989;39:1159–1165.

    Article  PubMed  CAS  Google Scholar 

  17. Berres M, Monsch AU, Bernasconi F, Thalmann B, Stahelin HB. Normal ranges of neuropsychological tests for the diagnosis of Alzheimer’s disease. Stud Health Technol Moral. 2000;77:195–199.

    CAS  Google Scholar 

  18. Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Perceptual and Motor Skills. 1958;8:271–276.

    Google Scholar 

  19. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984 Jul;34:939–944.

    Article  PubMed  CAS  Google Scholar 

  20. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry. 1994 Apr;57:416–418.

    Article  Google Scholar 

  21. McKeith IG. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis. 2006;9:417–423.

    PubMed  Google Scholar 

  22. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Worlshop. Neurology. 1993 Feb;43:250–260.

    CAS  Google Scholar 

  23. Fischer P, Krampla W, Mostafaie N, Zehetmayer S, Rainer M, Jungwirth S, Huber K, Bauer K, Hruby W, et al. VITA study: white matter hyperintensities of vascular and degenerative origin in the elderly. J Neural Transm Suppl. 2007;181–188.

  24. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149:351–356.

    PubMed  CAS  Google Scholar 

  25. Scheltens P, Barkhof F, Leys D, Pruvo JP, Nauta JJ, Veraiersch P, Steinling M, Valk J. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci. 1993 Jan;114:7–12.

    Article  PubMed  CAS  Google Scholar 

  26. Bracco L, Piccini C, Manfredi G, Fonda C, Falcini M, Amaducci L. Magnetic resonance measures in Alzheimer disease: their utility in early diagnosis and evaluating disease progression. Alzheimer Dis Assoc Disord. 1999 Jul;13:157–164.

    Article  PubMed  CAS  Google Scholar 

  27. Fox NC, Freeborough PA, Rossor MN. Visualisation and quantification of rates of atrophy in Alzheimer’s disease. Lancet. 1996 Jul 13:348:94–97.

    Article  PubMed  CAS  Google Scholar 

  28. Luxenberg JS, Haxby JV, Creasey H, Sundaram M, Rapoport SI. Rate of ventricular enlargement in dementia of the Alzheimer type correlates with rate of neuropsychological deterioration. Neurology. 1987 Jul;37:1135–1140.

    Article  PubMed  CAS  Google Scholar 

  29. Meese W, Kluge W, Grumme T, Hopfenmuller W. CT evaluation of the CSF spaces of healthy persons. Neuroradiology. 1980 Apr;19:131–136.

    Article  PubMed  CAS  Google Scholar 

  30. Huber KR, Mostafaie N, Stangl G, Worofka B, Kittl E, Hofmann J, Hejtman M, Michael R, Weissgram S, et al. Clinical chemistry reference values for 75-year-old apparently healthy persons. Clin ChemLabMed. 2006;44:1355–1360.

    CAS  Google Scholar 

  31. Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive impairment to dementia-meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand. 2009 Apr;l 19:252–265.

    Article  Google Scholar 

  32. Ganguli M, Snitz BE, Saxton JA, Chang CC, Lee CW, Vander BJ, Hughes TF, Loewenstein DA, Unverzagt FW, Petersen RC. Outcomes of mild cognitive impairment by definition: a population study. Arch Neurol. 2011 Jun;68:761–767.

    Article  PubMed  Google Scholar 

  33. Manly JJ, Tang MX, Schupf N, Stern Y, Vonsattel JP, Mayeux R. Frequency and course of mild cognitive impairment in a multiethnic community. Ann Neurol. 2008 Apr;63:494–506.

    Article  PubMed  Google Scholar 

  34. Annerbo S, Wahlund LO, Lokk J. The relation between homocysteine levels and development of Alzheimer’s disease in mild cognitive impairment patients. Dement Geriatr Cogn Disord. 2005;20:209–214.

    Article  PubMed  CAS  Google Scholar 

  35. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. 2007 Jan;64:86–92.

    Article  PubMed  Google Scholar 

  36. Brown B, Huang MH, Karlamangla A, Seeman T, Kado D. Do the effects of APOE-epsilon4 on cognitive function and decline depend upon vitamin status? MacArthur Studies of Successful Aging. J Nutr Health Aging. 2011 Mar;15:196–201.

    Article  PubMed  CAS  Google Scholar 

  37. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Tettamanti M, Lucca U. Homocysteine and B vitamins in mild cognitive impairment and dementia. Clin Chem Lab Med. 2005;43:1096–1100.

    Article  PubMed  CAS  Google Scholar 

  38. Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de JC, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71:826–832.

    Article  PubMed  CAS  Google Scholar 

  39. Seshadri S, Wolf PA, Beiser AS, Selhub J, Au R, Jacques PF, Yoshita M, Rosenberg IH, D’Agostino RB, DeCarli C. Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study. Arch Neurol. 2008 May;65:642–649.

    Article  PubMed  Google Scholar 

  40. Sachdev PS, Parslow R, Wen W, Anstey KJ, Easteal S. Sex differences in the causes and consequences of white matter hyperintensities. Neurobiol Aging. 2009 Jun;30:946–956.

    Article  PubMed  CAS  Google Scholar 

  41. de Lau LM, Smith AD, Refsum H, Johnston C, Breteler MM. Plasma vitamin B12 status and cerebral white-matter lesions. J Neurol Neurosurg Psychiatry. 2009 Feb;80:149–157.

    Article  PubMed  Google Scholar 

  42. Bradburn NM, Rips O, Shevell SK. Answering autobiographical questions: the in pact of memory and inference on surveys. Science. 1987 Apr 10;236:157–161.

    Article  Google Scholar 

  43. Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB. A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. J Nutr Health Aging. 2010 Mar;14:224–230.

    Article  PubMed  CAS  Google Scholar 

  44. Mooijaart SP, Gussekloo J, Frolich M, Jolles J, Stott DJ, Westendorp RG, de Craen AJ. Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study. Am J Clin Nutr. 2005 Oct;82:866–871.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Imrich Blasko.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blasko, I., Hinterberger, M., Kemmler, G. et al. Conversion from mild cognitive impairment to dementia: Influence of folic acid and vitamin B12 use in the vita cohort. J Nutr Health Aging 16, 687–694 (2012). https://doi.org/10.1007/s12603-012-0051-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-012-0051-y

Key words

Navigation