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The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills

Abstract

A polymorphism (Val66Met) in the gene encoding brain-derived neurotrophic factor (BDNF) has previously been associated with impaired hippocampal function and scores on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R). Despite its widespread expression in the brain, there have been few studies examining the role of BDNF on cognitive domains, other than memory. We examined the association between BDNF Val66Met genotype and non-verbal reasoning, as measured by Raven's standard progressive matrices (Raven), in two cohorts of relatively healthy older people, one aged 79 (LBC1921) and the other aged 64 (ABC1936) years. LBC1921 and ABC1936 subjects had reasoning measured at age 11 years, using the Moray House Test (MHT), in the Scottish Mental Surveys of 1932 and 1947, respectively. BDNF genotype was significantly associated with later life Raven scores, controlling for sex, age 11 MHT score and cohort (P=0.001). MHT, Verbal Fluency and Logical Memory scores were available, in later life, for LBC1921 only. BDNF genotype was significantly associated with age 79 MHT score, controlling for sex and age 11 MHT score (P=0.016). In both significant associations, Met homozygotes scored significantly higher than heterozygotes and Val homozygotes. This study indicates that BDNF genotype contributes to age-related changes in reasoning skills, which are closely related to general intelligence.

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Acknowledgements

We thank Martha Whiteman and Alison Pattie who collected phenotype data on the LBC1921 subjects. We thank Jen Herbert and others who collected phenotype data on the ABC1936 subjects. This project was funded by the United Kingdom Biotechnology and Biological Sciences Research Council. Ian Deary holds a Royal Society-Wolfson Research Merit award.

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Correspondence to S E Harris or I J Deary.

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Harris, S., Fox, H., Wright, A. et al. The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills. Mol Psychiatry 11, 505–513 (2006). https://doi.org/10.1038/sj.mp.4001799

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