A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show  KL-VS heterozygotes had shorter survival and  smaller white matter volumes than non-carriers;  had slower cognitive decline; and  had greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected. A possible explanation for these results in the context of the literature is a potential interaction between the environment and/or age of the participants, leading to a heterozygote disadvantage. The longitudinal cognitive trajectories indicate that heterozygotes would have an advantage in very late life. Collectively these results suggest that the genotype-survival advantage of the KL-VS allele is age-dependent and possibly mediated through differential cognition and brain volume.
- cognitive aging
- brain atrophy