Homocysteine and cognitive performance in the Framingham Offspring Study: Age is important

Merrill F. Elias, Lisa M. Sullivan, Ralph B. D'Agostino, Penelope K. Elias, Paul F. Jacques, Jacob Selhub, Sudha Seshadri, Rhoda Au, Alexa Beiser, Philip A. Wolf

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

Original languageEnglish (US)
Pages (from-to)644-653
Number of pages10
JournalAmerican journal of epidemiology
Issue number7
StatePublished - Oct 2005
Externally publishedYes


  • Aging
  • Cognition
  • Folic acid
  • Homocysteine
  • Memory disorders
  • Risk factors
  • Vitamin B 12
  • Vitamin B 6

ASJC Scopus subject areas

  • Epidemiology


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