White matter integrity in the splenium of the corpus callosum is related to successful cognitive aging and partly mediates the protective effect of an ancestral polymorphism in ADRB2.

It has recently been reported that the evolutionarily ancestral alleles of two functional polymorphisms in the beta(2)-adrenergic receptor gene (ADRB2) were related to higher cognitive ability in the 70 year old participants of the Lothian Birth Cohort 1936 (LBC1936). One emerging important factor in cognitive aging is the integrity of white matter tracts in the brain. Here, we used diffusion tensor MRI-based tractography to assess the integrity of eight white matter tracts in a subsample of the LBC1936. Higher integrity of the splenium of the corpus callosum predicted better cognitive ability in old age, even after controlling for IQ at age 11. Also, the ancestral allele of one ADRB2 SNP was associated with both splenium integrity and better cognitive aging. While the effects of the SNP and splenium integrity on cognitive aging were largely independent, there was some evidence for a partial mediation effect of ADRB2 status via splenium integrity.