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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Abstract

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
Volume55
Early online date7 Mar 2017
DOIs
Publication statusPublished - Jul 2017

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Aptitude
Heterozygote
Atrophy
Parturition
Cognition
Brain
Alleles
Frontal Lobe
Genotype
Health
White Matter

Keywords

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

Cite this

@article{e482691a9a954e68b91b3af3937849cb,
title = "Klotho, APOEε4, cognitive ability, brain size, atrophy and survival: A study in the Aberdeen Birth Cohort of 1936",
abstract = "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.",
keywords = "klotho, cognitive aging, brain atrophy, survival, APOEε4",
author = "{de Vries}, {Clarisse Florence} and Staff, {Roger T.} and Harris, {Sarah E.} and Dorota Chapko and Williams, {Daniel S.} and Polina Reichert and Trevor Ahearn and McNeil, {Christopher J.} and Whalley, {Lawrence J.} and Murray, {Alison D.}",
note = "We thank the cohort participants who contributed to these studies. The study was supported by the University of Aberdeen Development Trust; the UK’s Biotechnology and Biological Sciences Research Council (BBSRC); the Wellcome Trust; the Chief Scientist Office (Scotland); and the Alzheimer’s Research Trust (now ARUK).",
year = "2017",
month = "7",
doi = "10.1016/j.neurobiolaging.2017.02.019",
language = "English",
volume = "55",
pages = "91--98",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",

}

TY - JOUR

T1 - Klotho, APOEε4, cognitive ability, brain size, atrophy and survival

T2 - A study in the Aberdeen Birth Cohort of 1936

AU - de Vries, Clarisse Florence

AU - Staff, Roger T.

AU - Harris, Sarah E.

AU - Chapko, Dorota

AU - Williams, Daniel S.

AU - Reichert, Polina

AU - Ahearn, Trevor

AU - McNeil, Christopher J.

AU - Whalley, Lawrence J.

AU - Murray, Alison D.

N1 - We thank the cohort participants who contributed to these studies. The study was supported by the University of Aberdeen Development Trust; the UK’s Biotechnology and Biological Sciences Research Council (BBSRC); the Wellcome Trust; the Chief Scientist Office (Scotland); and the Alzheimer’s Research Trust (now ARUK).

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - klotho

KW - cognitive aging

KW - brain atrophy

KW - survival

KW - APOEε4

U2 - 10.1016/j.neurobiolaging.2017.02.019

DO - 10.1016/j.neurobiolaging.2017.02.019

M3 - Article

C2 - 28431289

VL - 55

SP - 91

EP - 98

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -