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American Journal of Epidemiology Advance Access published online on August 17, 2005
American Journal of Epidemiology, doi:10.1093/aje/kwi259
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved
Received January 25, 2005
Accepted April 28, 2005

Article

Homocysteine and Cognitive Performance in the Framingham Offspring Study: Age Is Important

Merrill F. Elias 1*, Lisa M. Sullivan 2, Ralph B. D'Agostino 3, Penelope K. Elias 1, Paul F. Jacques 4, Jacob Selhub 4, Sudha Seshadri 5, Rhoda Au 5, Alexa Beiser 6, and Philip A. Wolf 5

1 The Statistics and Consulting Unit, Department of Mathematics and Statistics, Boston University, Boston, MA; Department of Psychology, University of Maine, Orono, ME
2 The Statistics and Consulting Unit, Department of Mathematics and Statistics, Boston University, Boston, MA; Department of Biostatistics, Boston University School of Public Health, Boston, MA
3 The Statistics and Consulting Unit, Department of Mathematics and Statistics, Boston University, Boston, MA
4 The Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA
5 Department of Neurology, Boston University School of Medicine, Boston, MA
6 Department of Biostatistics, Boston University School of Public Health, Boston, MA

* To whom correspondence should be addressed.
Merrill F. Elias, E-mail: MFElias{at}aol.com


  Abstract

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.

Keywords: aging; cognition; folic acid; homocysteine; memory disorders; risk factors; vitamin B 6; vitamin B 12.
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