Longevity Klotho gene polymorphism and the risk of dementia in older men.

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).