Association of Serum Klotho with Cognitive Function Among Individuals with Nonalcoholic Fatty Liver Disease

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2024 Nov 20

PMID 39563739

Authors

Feilong Wu

Jie Pan

Mingtao Chen

Xuye Lai

Yingying Gu

Lei Pei

Lili Yang

Affiliations

Soon will be listed here.

Abstract

Introduction: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD).

Materials And Methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores.

Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered.

Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.

References

Zhao Y, Zeng C, Li X, Yang T, Kuang X, Du J . Klotho overexpression improves amyloid-β clearance and cognition in the APP/PS1 mouse model of Alzheimer's disease. Aging Cell. 2020; :e13239. PMC: 7576297. DOI: 10.1111/acel.13239. View

Morris J, HEYMAN A, Mohs R, Hughes J, van Belle G, Fillenbaum G . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989; 39(9):1159-65. DOI: 10.1212/wnl.39.9.1159. View

Seo S, Gottesman R, Clark J, Hernaez R, Chang Y, Kim C . Nonalcoholic fatty liver disease is associated with cognitive function in adults. Neurology. 2016; 86(12):1136-42. PMC: 4820136. DOI: 10.1212/WNL.0000000000002498. View

Riazi K, Azhari H, Charette J, Underwood F, King J, Afshar E . The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022; 7(9):851-861. DOI: 10.1016/S2468-1253(22)00165-0. View

Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M . Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015; 64(1):73-84. DOI: 10.1002/hep.28431. View

Gold P, Licinio J, Pavlatou M . Pathological parainflammation and endoplasmic reticulum stress in depression: potential translational targets through the CNS insulin, klotho and PPAR-γ systems. Mol Psychiatry. 2012; 18(2):154-65. PMC: 10064987. DOI: 10.1038/mp.2012.167. View

Fillenbaum G, van Belle G, Morris J, Mohs R, Mirra S, Davis P . Consortium to Establish a Registry for Alzheimer's Disease (CERAD): the first twenty years. Alzheimers Dement. 2008; 4(2):96-109. PMC: 2808763. DOI: 10.1016/j.jalz.2007.08.005. View

Castner S, Gupta S, Wang D, Moreno A, Park C, Chen C . Longevity factor klotho enhances cognition in aged nonhuman primates. Nat Aging. 2023; 3(8):931-937. PMC: 10432271. DOI: 10.1038/s43587-023-00441-x. View

Pei Y, Miu M, Mao X, Chen W, Zhu J . -Klotho: An Early Risk-Predictive Biomarker for Acute Kidney Injury in Patients with Acute Myocardial Infarction. Int J Clin Pract. 2024; 2023:8244545. PMC: 10771924. DOI: 10.1155/2023/8244545. View

10.

Thomas J, Kendall B, El-Serag H, Thrift A, Macdonald G . Hepatocellular and extrahepatic cancer risk in people with non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol. 2024; 9(2):159-169. DOI: 10.1016/S2468-1253(23)00275-3. View

11.

Linghui D, Simin Y, ZiLong Z, Yuxiao L, Shi Q, Birong D . The relationship between serum klotho and cognitive performance in a nationally representative sample of US adults. Front Aging Neurosci. 2023; 15:1053390. PMC: 9932504. DOI: 10.3389/fnagi.2023.1053390. View

12.

Liu Y, Chen M . Emerging role of α-Klotho in energy metabolism and cardiometabolic diseases. Diabetes Metab Syndr. 2023; 17(10):102854. DOI: 10.1016/j.dsx.2023.102854. View

13.

Gao X, Li Y, Sun Z, Xu H, Ma G, Deng Q . Could α-Klotho Unlock the Key Between Depression and Dementia in the Elderly: from Animal to Human Studies. Mol Neurobiol. 2021; 58(6):2874-2885. DOI: 10.1007/s12035-021-02313-0. View

14.

Wang Y, Sun Z . Current understanding of klotho. Ageing Res Rev. 2008; 8(1):43-51. PMC: 2637560. DOI: 10.1016/j.arr.2008.10.002. View

15.

Duell P, Welty F, Miller M, Chait A, Hammond G, Ahmad Z . Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2022; 42(6):e168-e185. DOI: 10.1161/ATV.0000000000000153. View

16.

Zhang H, Yu L, Yun G . Reduced Serum Levels of Klotho are Associated with Mild Cognitive Impairment in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes. 2023; 16:129-137. PMC: 9851628. DOI: 10.2147/DMSO.S394099. View

17.

Golabi P, Owrangi S, Younossi Z . Global perspective on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis - prevalence, clinical impact, economic implications and management strategies. Aliment Pharmacol Ther. 2024; 59 Suppl 1:S1-S9. DOI: 10.1111/apt.17833. View

18.

Orellana A, Mazucanti C, Dos Anjos L, de Sa Lima L, Kawamoto E, Scavone C . Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons. Sci Rep. 2023; 13(1):15080. PMC: 10497516. DOI: 10.1038/s41598-023-41166-6. View

19.

Xu Y, Sun Z . Molecular basis of Klotho: from gene to function in aging. Endocr Rev. 2015; 36(2):174-93. PMC: 4399270. DOI: 10.1210/er.2013-1079. View

20.

Rinella M, Lazarus J, Ratziu V, Francque S, Sanyal A, Kanwal F . A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol. 2023; 29(1):101133. DOI: 10.1016/j.aohep.2023.101133. View