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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.

SUBMITTER: Wu Y

PROVIDER: S-EPMC10620156 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

Wu Yue Y Lei Shaoyuan S Li Dongxiao D Li Zhongzhong Z Zhang Yingzhen Y Guo Yansu Y

Translational psychiatry 20231101 1

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 ...[more]

PMID: 37914711

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Project description:BackgroundPrevious meta-analyses have demonstrated osteoarthritis (OA) is associated with an increased risk of dementia, but these studies were prone to bias based on residual confounding factors and reverse causality.ObjectivesWe aimed to investigate associations between OA and cognitive function using data from the National Health and Nutrition Examination Survey (NHANES) and to investigate the causality using Mendelian randomization (MR).DesignThis is a cross-sectional study and MR study.MethodsData from the NHANES 2011-2014 were used. Multiple linear, logistic regressions and stratified analyses were used to determine the association between OA status and cognitive function. Sample weights were used to ensure result generalizability. Two-sample MR analysis was conducted to examine the association between OA and dementia. Mediation analyses were performed to investigate the mediating effects of depression.ResultsWe did not demonstrate a significant association between OA and cognitive performance after adjusting for relevant covariates (p > 0.05), and the population of individuals with both OA and depression was associated with higher odds of low total word recall cognitive performance (odds ratio (OR) = 4.74, 95% confidence interval (CI): 1.09-20.63; p = 0.04). Genetically predicted specific-site OA was not significantly associated with the risk of dementia (OR = 1.12; 95% CI: 0.96-1.32; p = 0.16), Alzheimer's disease (OR = 0.95, 95% CI: 0.68-1.31, p = 0.74), vascular dementia (OR = 1.32, 95% CI: 0.82-2.13, p = 0.25) with accepted heterogeneity and no evidence of directional pleiotropy. Furthermore, major depression was found to mediate the pathway between OA and vascular dementia (β = 0.044, 95% CI: -0.391 to 0.479, p < 0.05).ConclusionOur findings indicate that there is no significant association or causal relationship between OA and cognitive decline. However, depression may serve as an important factor influencing cognitive outcomes. Future research should further explore the bidirectional causal relationship and underlying mechanisms.

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Dataset Information

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

Publications

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

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