{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:39:30Z","timestamp":1783489170483,"version":"3.55.0"},"reference-count":67,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,8,29]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>It is well established that mid-life hypertension increases risk of dementia, whereas the association of late-life hypertension with dementia is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To determine whether FOXO3 longevity-associated genotype influences the association between late-life hypertension and incident dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Subjects were 2,688 American men of Japanese ancestry (baseline age: 77.0\u00b14.1 years, range 71\u201393 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\u2019s disease (AD) was assessed using Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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, APOE \u025b4, and cardiovascular risk factors, showed late-life hypertension increased VaD risk only (HR\u200a=\u200a1.71, 95% CI\u200a=\u200a1.08\u20132.71, p\u200a=\u200a0.022). 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, APOE \u025b4, and other cardiovascular risk factors, there was a significant interaction effect of late-life hypertension and FOXO3 longevity genotype on incident AD ( \u03b2=\u200a\u20130.52, p\u200a=\u200a0.0061). In men with FOXO3 rs2802292 longevity genotype ( TG\/ GG), late-life hypertension showed protection against AD (HR\u200a=\u200a0.72; 95% CI\u200a=\u200a0.55\u20130.95, p\u200a=\u200a0.021). The non-longevity genotype ( TT) (HR\u200a=\u200a1.16; 95% CI\u200a=\u200a0.90\u20131.51, p\u200a=\u200a0.25) had no protective effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This longitudinal study found late-life hypertension was associated with lower incident AD in subjects with FOXO3 genotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230350","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T12:18:21Z","timestamp":1689682701000},"page":"79-91","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Incidence of Alzheimer\u2019s Disease in Men with Late-Life Hypertension Is Ameliorated by\n                    <i>FOXO3<\/i>\n                    Longevity Genotype"],"prefix":"10.1177","volume":"95","author":[{"given":"Randi","family":"Chen","sequence":"first","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2468-3566","authenticated-orcid":false,"given":"Brian J.","family":"Morris","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"School of Medical Sciences, University of Sydney, Sydney, NSW, Australia"},{"name":"Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Donlon","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Webster","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"},{"name":"Veterans Affairs Pacific Islands Health Care Systems, Honolulu, HI, USA"},{"name":"Pacific Health Research and Education Institute, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana J.","family":"Kallianpur","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Allsopp","sequence":"additional","affiliation":[{"name":"Institute for Biogenesis Research, University of Hawaii, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"},{"name":"Neuroscience Institute, The Queen\u2019s Medical Center, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Willcox","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal H.","family":"Masaki","sequence":"additional","affiliation":[{"name":"NIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA"},{"name":"Department of Geriatric Medicine, John A. 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