Serum Klotho and Cognitive Functioning in Older Adults Aged 60 and 79: The National Health and Nutrition Examination Survey 2011 to 2014

Abstract

Abstract Objectives Klotho is found to be associated with better cognitive outcomes in selected small sample of aged population. We aimed to examine the association of serum klotho with cognitive function among older adults using a nationally representative sample of the U.S. Method A total of 2,173 older adults aged 60–79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included. Klotho was measured and quantified in laboratory. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest [CERAD-WL] immediate and delayed memory, the Animal Fluency test [AFT], the Digit Symbol Substitution Test [DSST]). Test-specific and global cognition z-scores were calculated based on means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles of serum klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. Results Serum klotho level in the lowest quartile was associated with lower z-score for DSST (beta (β)=-0.13, 95% confidence interval (CI): -0.25, -0.01). For subgroup analysis, serum klotho level in the lowest quartile was associated with lower z-scores for DSST (β=-0.16, 95% CI: -0.32, -0.003) and global cognition (β=-0.14, 95% CI: -0.28, -0.01) among women. No significant association was found among men. Conclusions Low serum klotho was associated with poorer cognitive function, particularly among women. Future studies are expected to examine the longitudinal associations between klotho levels and cognitive outcomes.