American Journal of Epidemiology Advance Access originally published online on July 16, 2007
American Journal of Epidemiology 2007 166(6):672-678; doi:10.1093/aje/kwm140
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ORIGINAL CONTRIBUTIONS |
Methylenetetrahydrofolate Reductase C677T Polymorphism and Cognitive Function in Older Women
1 Department of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA
2 Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA
3 Department of Medicine, School of Medicine, University of California, San Francisco, San Francisco, CA
4 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
5 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
6 Department of Psychiatry, School of Medicine, University of California, San Francisco, San Francisco, CA
Correspondence to Dr. Jacob S. Elkins, Box 114, Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, M-798, San Francisco, CA 94143 (e-mail: jacob.elkins{at}ucsfmedctr.org).
Received for publication June 28, 2006. Accepted for publication March 19, 2007.
Homocysteine may play a causal role in cognitive decline. The authors analyzed the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a correlate of plasma homocysteine levels, among 6,653 participants in the Study of Osteoporotic Fractures, a community-based, prospective cohort study of older women in four US states. During the years 1986–1998, the authors assessed whether the distribution of MTHFR C677T genotypes was independent of potential confounders and whether persons with the TT genotype had lower baseline performance or showed greater longitudinal declines on standard cognitive tests. Although ethnicity was associated with MTHFR genotype distribution within the entire cohort (p < 0.001), all measured confounders appeared independent of MTHFR genotype within the largest ethnically homogenous subgroup, persons of Northern and/or Central European ancestry (n = 5,668) (Kolmogorov-Smirnov p = 0.97). In this subgroup, the TT genotype was associated with lower scores on the Digit Symbol Substitution Test (p = 0.034) and the Trails B test (p = 0.020) and with a small excess annual decline on a modified version of the Mini-Mental State Examination (p = 0.035). Although the strength of the observed associations was modest, these results lend some support to the theory that an elevated homocysteine level contributes to cognitive decline.
aging; cognition disorders; homocysteine; methylenetetrahydrofolate reductase (NADPH2); random allocation
Abbreviations: CI, confidence interval; DSST, Digit Symbol Substitution Test; mMMSE, modified Mini-Mental State Examination; MTHFR, 5,10-methylenetetrahydrofolate reductase