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).