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

doi:10.1016/j.neurobiolaging.2017.02.019

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 language	English
Pages (from-to)	91-98
Number of pages	8
Journal	Neurobiology of Aging
Volume	55
Early online date	7 Mar 2017
DOIs	https://doi.org/10.1016/j.neurobiolaging.2017.02.019
Publication status	Published - Jul 2017

Bibliographical 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).

Keywords

klotho
cognitive aging
brain atrophy
survival
APOEε4

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© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 1.45 MBLicence: CC BY-NC-ND

Aberdeen Birth Cohort Study 1936 (ABC 1936)
Craig, L. (Data Manager), University of Aberdeen, 1997
http://www.abdn.ac.uk/aberdeen-birth-cohort/ and one more link, https://www.abdn.ac.uk/birth-cohorts/1936/for-researchers/data-access/?action=subpage (show fewer)
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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{\textquoteright}s Biotechnology and Biological Sciences Research Council (BBSRC); the Wellcome Trust; the Chief Scientist Office (Scotland); and the Alzheimer{\textquoteright}s Research Trust (now ARUK).",

year = "2017",

month = jul,

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",

}

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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

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DO - 10.1016/j.neurobiolaging.2017.02.019

M3 - Article

C2 - 28431289

SN - 0197-4580

VL - 55

SP - 91

EP - 98

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Bibliographical note

Keywords

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Datasets

Aberdeen Birth Cohort Study 1936 (ABC 1936)

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