Journal
NEUROBIOLOGY OF AGING
Volume 55, Issue -, Pages 91-98Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.02.019
Keywords
Klotho; Cognitive aging; Brain atrophy; Survival; APOE epsilon 4
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Funding
- University of Aberdeen Development Trust [DT OL1134]
- UK's Biotechnology and Biological Sciences Research Council (BBSRC) [BB/K000195]
- Wellcome Trust [064359 2000/01]
- Chief Scientist Office (Scotland) [CZH/4/131]
- ARUK [ART/SPG2003B]
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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 that, relative to noncarriers, KL-VS heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3) slower cognitive decline; and (4) 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. (C) 2017 Elsevier Inc. All rights reserved.
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