{"doi":"10.1101/2024.07.20.24310745","title":"Impact of <i>APOE</i> , <i>Klotho</i> and sex on cognitive decline with aging","abstract":"Abstract The effects of 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 (ε4/ε3 &amp; ε3/ε3) as well as smaller hippocampi and amygdala ( N = 37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) 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.","journal":"medRxiv","year":2024,"id":501295,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353717,"name":"Cheng Chen","orcid":"0009-0001-8818-6713","position":1,"is_corresponding":false},{"id":724548,"name":"Xin You Tai","orcid":"0000-0002-7333-2204","position":2,"is_corresponding":false},{"id":852852,"name":"Sanjay Manohar","orcid":"0000-0003-0735-4349","position":3,"is_corresponding":false},{"id":811291,"name":"Masud Husain","orcid":"0000-0002-6850-9255","position":4,"is_corresponding":false},{"id":1350538,"name":"Kengo Shibata","orcid":"0000-0002-6156-426X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:12.068207Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}