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

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.