Homocysteine and holo-transcobalamin and the risk of dementia and Alzheimers disease: a prospective study

Eur J Neurol. 2009 Jul;16(7):808-13. doi: 10.1111/j.1468-1331.2009.02590.x. Epub 2009 Apr 21.


Background: Elevated total homocysteine (tHcy) levels may be caused by vitamin B12 deficiency and are linked to Alzheimers disease (AD) in some studies, although the evidence is mixed. Another marker of vitamin B12 deficiency, holo-transcobalamin (holo-TC), has not been studied in a prospective setting.

Objective: To investigate the association between tHcy and holo-TC and the subsequent development of dementia and AD in a prospective study.

Methods: A sub-sample of 228 non-demented subjects was taken from the Kungsholmen Project, a population-based longitudinal study amongst persons 75+ years. tHcy and holo-TC were analysed at baseline.

Results: Increasing tHcy levels were related to an increased risk of dementia (n = 83) and AD (n = 61) after a mean follow-up time of 6.7 years. Persons with high tHcy (the fourth quartile) had more than twice as high a risk of developing AD than persons with low tHcy, even after adjusting for confounding or mediating factors. The third quartile of holo-TC was associated with a reduced risk of AD, after adjusting for Hcy and other confounders.

Conclusions: These results suggest that Hcy is involved in the development of dementia and AD. The role of holo-TC was less clear and this marker needs to be studied further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / metabolism*
  • Community Health Planning
  • Dementia / epidemiology*
  • Dementia / metabolism*
  • Female
  • Homocysteine / metabolism*
  • Humans
  • Male
  • Models, Anatomic
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Transcobalamins / metabolism*


  • Transcobalamins
  • Homocysteine