title: Methylenetetrahydrofolate reductase C677T polymorphism and cognitive function in older women.
abstract: 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.
authors.affiliation: Department of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. jacob.elkins@ucsfmedctr.org
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Elkins
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Deborah
authors.initials: D
authors.lastname: Kado
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D014481:United States / Q000453:epidemiology
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)