Relationship of Klotho with cognition and dementia: Results from the NHANES 2011–2014 and Mendelian randomization study

Abstract

The relationships of Klotho levels with cognition and dementia are poorly understood. This study aimed to investigate the association between Klotho levels and cognitive function and to determine causality between Klotho and dementia using Mendelian randomization (MR). Based on data from the National Health and Nutrition Survey (NHANES) 2011–2014, this study consisted of 1875 older adults aged 60–79 years. Cognitive function was assessed by the digit symbol substitution test (DSST). We performed weighted multivariable-adjusted linear regression to assess the association between Klotho concentrations and cognitive function. Then, 2-sample MR was conducted to assess the causal relationship between Klotho and dementia. The inverse variance weighted (IVW) method was used as the primary analysis. We observed a positive association between serum Klotho concentrations and the results of the Digit Symbol Substitution test (DSST) (T2: β 2.16, 95% CI: 0.30–4.01, P = 0.03, T3: β 2.48, 95% CI: 0.38–4.57, P = 0.02) after adjusting for the covariates. Moreover, there was also a potential nonlinear relationship between Klotho and DSST. The IVW method showed that genetically predicted high Klotho levels were not significantly associate with any type of dementia, including Alzheimer’s disease (OR = 1.03, 95% CI: 0.96–1.10, P = 0.46), vascular dementia (OR = 1.04, 95% CI: 0.87–1.25, P = 0.66), frontotemporal dementia (OR = 0.73, 95% CI: 0.47–1.14, P = 0.16), or dementia with Lewy bodies (OR = 1.03, 95% CI: 0.87–1.23, P = 0.73). In the cross-sectional observational study, Klotho and cognitive function were significantly correlated; however, findings from MR studies did not indicate a causal relationship between Klotho and dementia.

The association between polyunsaturated fatty acids and periodontitis: NHANES 2011–2014 and Mendelian randomisation analysis

“…However, some limitations need to be considered when interpreting our findings. First, the study sample consisted of individuals of American and European ancestry, which may limit the generalizability of the results to other ethnic groups [ 47 , 48 ]. Second, periodontitis samples may exhibit heterogeneity due to variations in the definitions of periodontal disease cases, potentially influencing the reliability and generalizability of our conclusions.…”

Sex Hormones and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study and Mendelian Randomization Analysis

“…Regarded as natural randomized, double-blind trials, MR is an emerging research method that applies single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore the possible causal relationship between exposure and outcome. 18 , 19 MR analysis may provide more reliable causal results by reducing the possible influence caused by potential confounders. 18 , 19 By adding MR in this research, we may reach an in-depth understanding of the relationship between sex hormones and COPD.…”

“… 18 , 19 MR analysis may provide more reliable causal results by reducing the possible influence caused by potential confounders. 18 , 19 By adding MR in this research, we may reach an in-depth understanding of the relationship between sex hormones and COPD.…”