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Keywords:

  • aged;
  • cognition;
  • folic acid;
  • humans;
  • methylmalonic acid;
  • vitamin B 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.