Klotho, APOEε4, cognitive ability, brain size, atrophy and survival: A study in the Aberdeen Birth Cohort of 1936

Clarisse Florence de Vries, Roger T. Staff, Sarah E. Harris, Dorota Chapko, Daniel S. Williams, Polina Reichert, Trevor Ahearn, Christopher J. McNeil, Lawrence J. Whalley, Alison D. Murray

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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 [1] KL-VS heterozygotes had shorter survival and [2] smaller white matter volumes than non-carriers; [3] had slower cognitive decline; and [4] 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.
Original languageEnglish
Pages (from-to)91-98
Number of pages8
JournalNeurobiology of Aging
Early online date7 Mar 2017
Publication statusPublished - Jul 2017



  • klotho
  • cognitive aging
  • brain atrophy
  • survival
  • APOEε4

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