MTHFR polymorphisms and cognitive ageing in the ninth decade: the Lothian Bith Cohort 1921

Olga J.G. Schiepers, Martin P.J. van Boxtel, Sarah E. Harris, Alan Gow, Alison Pattie, Caroline Brett, Renate De Groot, Jelle Jolles, John M. Starr, Ian J. Deary

    Research output: Contribution to journalArticleAcademicpeer-review


    Low blood levels of B vitamins have been implicated in age-associated cognitive impairment. The present study investigated the association between genetic variation in folate metabolism and age-related cognitive decline in the ninth decade of life. Both the 677C>T (rs1801133) polymorphism and the scarcely-studied 1298A>C (rs1801131) polymorphism of the MTHFR gene were assessed in relation to cognitive change over 8 years in older community-dwelling individuals. MTHFR genotype was determined in 476 participants of the Lothian Birth Cohort 1921, whose intelligence was measured in childhood in the Scottish Mental Survey of 1932. Cognitive performance on the domains of verbal memory, abstract reasoning, and verbal fluency was assessed at mean age 79 (n = 476), and again at mean ages of 83 (n = 275) and 87 (n = 180). Using linear mixed models, the MTHFR 677C>T and 1298A>C variants were not associated with the rate of cognitive change between 79 and 87 years, neither in the total sample, nor in a subsample of individuals with erythrocyte folate levels below the median. APOE E4 allele carrier status did not interact with MTHFR genotype in affecting change in cognitive performance over 8 years. In conclusion, MTHFR 677C>T and 1298A>C polymorphisms were not associated with individual change in cognitive functioning in the ninth decade of life. Although polymorphisms in the MTHFR gene may cause disturbances in folate metabolism, they do not appear to be accompanied by changes in cognitive functioning in old age.
    Original languageEnglish
    Pages (from-to)354-364
    Number of pages11
    JournalGenes, Brain and Behavior
    Issue number3
    Publication statusPublished - Apr 2011


    • Cognitive ageing
    • Lothian Birth Cohort
    • MTHFR polymorphisms
    • longitudinal
    • MTHFR
    • cohort study
    • intelligence
    • cognitive performance
    • ageing


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