Highlights
- •The Klotho (KL) gene encodes a membrane protein associated with the suppression of certain physiological aspects of ageing.
- •A common heterozygosity variant of the KL gene (KL-VS) improves cognitive function and could affect the risk of dementia.
- •This longitudinal study showed that the KL-VS variant increases the incidence of dementia in a dose-dependent fashion.
- •If these preliminary findings are confirmed, Klotho supplementation may have a role to play in the prevention of dementia.
Abstract
Introduction
Klotho variants (KL-VS) have been associated with increased longevity and better cognitive
function. It is unclear whether they modulate dementia risk.
Methods
We recruited 527 men aged 71–87 years who were free of cognitive impairment. We used
data linkage to track the onset of dementia over 10 years. KL-VS genotyping (rs9536314
T/G) followed standard procedures.
Results
The annual rate of dementia was 17.2‰ (95%CI = 14.0–21.1; total = 5053 person-years), and 14.0‰ (95%CI = 10.6–18.4; 3582 person-years), 23.5‰ (95%CI = 16.6–33.2; 1363 person-years) and 46.4‰ (95%CI = 19.3–111.5; 108 person-years) for men with the TT, TG and GG genotypes. Compared with
the TT genotype, the sub-hazard ratios of dementia associated with the TG and GG genotypes
were 1.6 (95%CI = 1.0, 2.5; p = 0.030) and 3.5 (95%CI = 1.3, 9.1; p = 0.011).
Discussion
The Klotho KL-VS variant is associated with an increase in the incidence of dementia
in older men, in a dose-dependent fashion (intermediate for heterozygosis and highest
for homozygosis).
Keywords
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Article info
Publication history
Published online: April 08, 2017
Accepted:
April 7,
2017
Received in revised form:
April 5,
2017
Received:
March 6,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
