Related Experiment Video
Updated: May 29, 2025

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach
Published on: February 14, 2014
Impact of APOE, Klotho, and sex on cognitive decline with aging
Kengo Shibata1, Cheng Chen2, Xin You Tai1,3
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.
Abstract:
The effects of apolipoprotein E (APOE) and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here, we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε3/ε4 and ε3/ε3) as well as smaller hippocampi and amygdala (N = 29,510). Critically, sex and age differentially affected the decline in cognition. Younger (40 to 50 y) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast, Klotho-VS heterozygosity did not affect cognition or brain volume, regardless of APOE genotype, sex, or age. These cognitive trajectories with aging demonstrate clear sex-dependent antagonistic pleiotropy effects of APOE ε4, but no effects of Klotho genotype on cognition and brain volume.
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