{"doi":"10.3233/jad-230350","title":"Incidence of Alzheimer’s Disease in Men with Late-Life Hypertension Is Ameliorated by <i>FOXO3</i> Longevity Genotype","abstract":"BACKGROUND: It is well established that mid-life hypertension increases risk of dementia, whereas the association of late-life hypertension with dementia is unclear. OBJECTIVE: To determine whether FOXO3 longevity-associated genotype influences the association between late-life hypertension and incident dementia. METHODS: Subjects were 2,688 American men of Japanese ancestry (baseline age: 77.0±4.1 years, range 71-93 years) from the Kuakini Honolulu Heart Program. Status was known for FOXO3 rs2802292 genotype, hypertension, and diagnosis of incident dementia to 2012. Association of FOXO3 genotype with late-life hypertension and incident dementia, vascular dementia (VaD) and Alzheimer's disease (AD) was assessed using Cox proportional hazards models. RESULTS: During 21 years of follow-up, 725 men were diagnosed with all-cause dementia, 513 with AD, and 104 with VaD. A multivariable Cox model, adjusting for age, education, APOEɛ4, and cardiovascular risk factors, showed late-life hypertension increased VaD risk only (HR = 1.71, 95% CI = 1.08-2.71, p = 0.022). We found no significant protective effect of FOXO3 longevity genotype on any type of dementia at the population level. However, in a full Cox model adjusting for age, education, APOEɛ4, and other cardiovascular risk factors, there was a significant interaction effect of late-life hypertension and FOXO3 longevity genotype on incident AD (β= -0.52, p = 0.0061). In men with FOXO3 rs2802292 longevity genotype (TG/GG), late-life hypertension showed protection against AD (HR = 0.72; 95% CI = 0.55-0.95, p = 0.021). The non-longevity genotype (TT) (HR = 1.16; 95% CI = 0.90-1.51, p = 0.25) had no protective effect. CONCLUSION: This longitudinal study found late-life hypertension was associated with lower incident AD in subjects with FOXO3 genotype.","journal":"Journal of Alzheimer s Disease","year":2023,"id":352812,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":773560,"name":"Brian J. Morris","orcid":"0000-0003-2468-3566","position":1,"is_corresponding":false},{"id":594991,"name":"Timothy A. Donlon","orcid":"0000-0001-6545-6533","position":2,"is_corresponding":false},{"id":343294,"name":"G. Webster Ross","orcid":null,"position":3,"is_corresponding":false},{"id":754714,"name":"Kalpana J. Kallianpur","orcid":"0000-0002-9978-097X","position":4,"is_corresponding":false},{"id":767123,"name":"Richard Allsopp","orcid":"0000-0001-7565-5325","position":5,"is_corresponding":false},{"id":917595,"name":"Kazuma Nakagawa","orcid":"0000-0002-8744-8531","position":6,"is_corresponding":false},{"id":390680,"name":"Bradley J. Willcox","orcid":"0000-0001-9890-3520","position":7,"is_corresponding":false},{"id":390515,"name":"Kamal Masaki","orcid":"0000-0003-1170-3118","position":8,"is_corresponding":false},{"id":372084,"name":"Randi Chen","orcid":"0000-0003-3747-7964","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:54.209378Z","pmid":"37483002","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":[]}