Klotho KL-VS haplotype does not improve cognition in a population-based sample of adults age 55–87 years

Müller, Bernhard W.; Hinney, Anke; Scherbaum, Norbert; Weimar, Christian; Kleinschnitz, Christoph; Peters, Triinu; Hochfeld, Lara; Pechlivanis, Sonali; Stang, Andreas; Jokisch, Martha; Kowall, Bernd

doi:10.1038/s41598-021-93211-x

Article / Chapter Mon Jul 5 2021 CC BY 4.0

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Klotho KL-VS haplotype does not improve cognition in a population-based sample of adults age 55–87 years

Müller, Bernhard W.; Hinney, Anke ; Scherbaum, Norbert ; Weimar, Christian ; Kleinschnitz, Christoph ; Peters, Triinu ; Hochfeld, Lara ; Pechlivanis, Sonali ; Stang, Andreas ; Jokisch, Martha ; Kowall, Bernd

The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

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Date Issued:

05.07.2021

URN:

urn:nbn:de:hbz:465-20240905-103236-9

DOI:

10.1038/s41598-021-93211-x

Language:

English

Type of Resource:

Text

Keywords:

Geriatrics; Haplotypes; Psychology; Public health

Collection:

E-Publications

Subject categories of the Deutsche Nationalbibliografie:

610 Medical sciences Medicine

Hosting institution:

Faculty of Medicine, Essen University Hospital, Institute of Medical Radiation Biology

Hosting institution:

Faculty of Medicine, Essen University Hospital, LVR-Klinikum Essen, Klinik für Psychiatrie und Psychotherapie

Hosting institution:

Faculty of Medicine, Essen University Hospital, Institute of Computer Science in Medicine, Biostatistics, and Epidemiology

Hosting institution:

Faculty of Medicine, Essen University Hospital, Clinic for Neurology

Hosting institution:

Scientific institutes, Center of Medical Biotechnology (ZMB)

funding:

The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.

Open Access funding enabled and organized by Projekt DEAL. The authors thank the Heinz Nixdorf Foundation [Chairman: Martin Nixdorf; Past Chairman: Dr jur. Gerhard Schmidt (†)], for their generous support of this study. Parts of the study were also supported by the German Research Council (DFG) [DFG project: EI 969/2-3, ER 155/6-1;6-2, HO 3314/2-1;2-2;2-3;4-3, INST 58219/32-1, JO 170/8-1, KN 885/3-1, PE 2309/2-1, SI 236/8-1;9-1;10-1], the German Ministry of Education and Science [BMBF project: 01EG0401, 01GI0856, 01GI0860, 01GS0820_WB2-C, 01ER1001D, 01GI0205], the Ministry of Innovation, Science, Research and Technology, North Rhine-Westphalia (MIWFT-NRW), the Else Kröner-Fresenius-Stiftung [project: 2015_A119] and the German Social Accident Insurance [DGUV project: FF-FP295]. Furthermore the study was supported by the Competence Network for HIV/AIDS, the deanship of the University Hospital and IFORES of the University Duisburg-Essen, the European Union, the German Competence Network Heart Failure, Kulturstiftung Essen, the Protein Research Unit within Europe (PURE), the Dr. Werner-Jackstädt Stiftung and the following companies: Celgene GmbH München, Imatron/GE-Imatron, Janssen, Merck KG, Philips, ResMed Foundation, Roche Diagnostics, Sarstedt AG&Co, Siemens HealthCare Diagnostics, Volkswagen Foundation.

Info on primary publication:

Müller, B.W., Hinney, A., Scherbaum, N. et al. Klotho KL-VS haplotype does not improve cognition in a population-based sample of adults age 55–87 years. Sci Rep 11, 13852 (2021). https://doi.org/10.1038/s41598-021-93211-x

Published 05 July 2021

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