Vitamin B-12 and folate status in relation to decline in scores on the mini-mental state examination in the framingham heart study

J Am Geriatr Soc. 2012 Aug;60(8):1457-64. doi: 10.1111/j.1532-5415.2012.04076.x. Epub 2012 Jul 12.


Objectives: To investigate the cognitive significance of low to low-normal plasma vitamin B-12 concentrations and to shed light on the role that folate status plays in the association between vitamin B-12 status and cognitive decline.

Design: Associations between plasma vitamin B-12 and folate and 8-year cognitive decline were evaluated, and the effects of interactions between vitamin B-12 status and folate status and supplemental folate use on cognitive decline were assessed.

Setting: The Framingham Heart Study - a prospective epidemiological study.

Participants: Five hundred forty-nine community-dwelling individuals aged 74.8 ± 4.6.

Measurements: Mini-Mental State Examination (MMSE), plasma folate, vitamin B-12, methylmalonic acid, homocysteine, demographic factors, and body mass index.

Results: MMSE scores declined by 0.24 points per year over the 8-year follow-up period. Decline was significantly faster in cohort members in the bottom two plasma vitamin B-12 quintile categories, and no apparent cognitive advantage was associated with plasma vitamin B-12 from 187 to 256.8 pmol/L over less than 186 pmol/L. In cohort members with plasma vitamin B-12 less than 258 pmol/L, having a plasma folate concentration greater than 20.2 nmol/L was associated with an approximate 1-point per year decline, as was use of supplemental folate.

Conclusion: Plasma vitamin B-12 levels from 187 to 256.8 pmol/L predict cognitive decline. Furthermore, having plasma vitamin B-12 levels in this range or below in conjunction with high plasma folate or supplemental folate use predicts especially rapid cognitive decline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Cognition Disorders / blood*
  • Cognition Disorders / diagnosis*
  • Female
  • Folic Acid / blood*
  • Humans
  • Male
  • Neuropsychological Tests
  • Prospective Studies
  • Vitamin B 12 / blood*


  • Folic Acid
  • Vitamin B 12