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

• Published in: Scientific reports Vol. 11; no. 1; pp. 13852 - 9
• Main Authors: Müller, Bernhard W., Hinney, Anke, Scherbaum, Norbert, Weimar, Christian, Kleinschnitz, Christoph, Peters, Triinu, Hochfeld, Lara, Pechlivanis, Sonali, Stang, Andreas, Jokisch, Martha, Kowall, Bernd
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/728; 631/477; 692/700/1518; 692/700/478; Adult; Age; Aged; Aged, 80 and over; Alleles; Attention; Cognition; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - epidemiology; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Female; Genotype; Geriatrics; Glucuronidase - genetics; Haplotypes; Haplotypes - genetics; Heterozygote; Heterozygotes; Humanities and Social Sciences; Humans; Klotho protein; Klotho Proteins; Male; Memory; Middle Aged; multidisciplinary; Neuropsychological Tests; Science; Science (multidisciplinary); Sensorimotor integration; Visual perception
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-93211-x

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.