{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:55:34Z","timestamp":1792266934470,"version":"4.4.0"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n There is limited research on the long-term associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) and dementia. No study has evaluated whether such associations vary by race or hormone therapy (HT) use.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To examine associations of baseline plasma p-tau217 with incident MCI and dementia and determine whether associations vary by age, race,\n APOE<\/jats:italic>\n \u03b54 carrier status, or HT use.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study examined women recruited from 39 US clinical sites between 1996 and 1999 into the Women\u2019s Health Initiative Memory Study who were randomized to either estrogen alone vs placebo or estrogen plus progestin vs placebo. Women were assessed for up to 25 years through 2021. Baseline plasma p-tau217 was measured in 2024 and analyzed between February and August 2025. Women aged 65 to 79 years who were cognitively unimpaired at baseline were included for this analysis.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Plasma p-tau217, quantified using the ALZpath Simoa assay.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the combined end point of incident MCI or probable dementia. Secondary outcomes included MCI and dementia examined separately. Cause-specific hazard ratios (HRs) and 95% CIs for the association of p-tau217 with MCI or dementia were estimated using Cox proportional hazards regression models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 2766 participants (mean [SD] age, 69.9 [3.8] years; 486 [17.9%] Black, 196 [7.1%] Hispanic, and 2007 [73.9%] White), 1311 developed the combined end point of MCI or dementia (849 participants with MCI and 752 participants with dementia). Every 1-SD increase in log\n 2<\/jats:sub>\n -transformed p-tau217 was associated with incident MCI or dementia (HR, 2.43; 95% CI, 2.18-2.71) and each individual outcome (MCI: HR, 1.94; 95% CI, 1.72-2.20; dementia: HR, 3.17; 95% CI, 2.79-3.61). Associations of p-tau217 with dementia were larger in magnitude for women randomized to estrogen plus progestin (HR, 4.18; 95% CI, 3.41-5.13) vs placebo (HR, 3.07; 95% CI, 2.41-3.91) (\n P<\/jats:italic>\n for interaction\u2009=\u2009.04) but did not significantly vary by estrogen alone vs placebo. P-tau217 associations with MCI or dementia were larger in magnitude for women older than 70 years (\n P<\/jats:italic>\n for interaction\u2009=\u2009.04),\n APOE<\/jats:italic>\n \u03b54 carriers (\n P<\/jats:italic>\n for interaction\u2009=\u2009.02), and White women compared with Black women (\n P<\/jats:italic>\n for interaction\u2009&amp;lt;\u2009.001). However, the combination of p-tau217 and age performed similarly in White women (area under the curve\u2009=\u200972.0%; 95% CI, 70.3%-73.6%) and Black women (area under the curve\u2009=\u200970.4%; 95% CI, 64.0%-78.0%). P-tau217 was not associated with incident MCI in Black women.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this cohort study of cognitively unimpaired older women, p-tau217 was associated with incident MCI or dementia up to 25 years later. These findings suggest that age, race,\n APOE<\/jats:italic>\n \u03b54, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.1295","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:00:27Z","timestamp":1773154827000},"page":"e261295","source":"Crossref","is-referenced-by-count":10,"title":["Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women"],"prefix":"10.1001","volume":"9","author":[{"given":"Aladdin H.","family":"Shadyab","sequence":"first","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human and Human Longevity Science, University of California San Diego, La Jolla"},{"name":"Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human and Human Longevity Science, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Z.","family":"LaCroix","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human and Human Longevity Science, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Mielke","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Resnick","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human and Human Longevity Science, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Towia A.","family":"Libermann","sequence":"additional","affiliation":[{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics, and Systems Biology Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ngo","sequence":"additional","affiliation":[{"name":"Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Casanova","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P.","family":"Reiner","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Nievergelt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam X.","family":"Maihofer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda K.","family":"McEvoy","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"12","key":"zoi260069r1","doi-asserted-by":"publisher","first-page":"5805","DOI":"10.1002\/alz.13455","article-title":"The potential clinical value of plasma biomarkers in Alzheimer\u2019s disease.","volume":"19","author":"Blennow","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"4","key":"zoi260069r2","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1093\/brain\/awac333","article-title":"Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer\u2019s 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