biostudies-literatureUnknownShadyab AHNIA NIH HHSNHLBI NIH HHSWHI NIH HHSNo study has evaluated whether associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) or dementia vary by race or hormone therapy (HT) use. We examined 2,766 cognitively unimpaired women ≥65 years randomized to HT vs placebo with 25-year follow-up. P-tau217 was associated with incident MCI/dementia (hazard ratio [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 between p-tau217 and dementia were stronger for women randomized to estrogen plus progestin vs placebo (HR, 4.18; 95% CI, 3.41-5.13 vs HR, 3.07; 95% CI, 2.41-3.91, respectively; <i>P</i> interaction=0.044) but did not vary for estrogen alone vs placebo. The combination of p-tau217 and age performed similarly in White and Black women (AUC=72.0% and 70.4%, respectively). Findings show the value of plasma p-tau217 for prediction of MCI and dementia up to 25 years in advance in older women.medRxiv : the preprint server for health sciences2025.10.30.25339146https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636631biostudies-literaturePlasma p-tau217 and incident mild cognitive impairment and dementia in older women: 25-year prospective study in The Women's Health Initiative Memory Study.PMC12636631U24 AG082930R01 AG07914975N92021D0000175N92021D0000275N92021D0000375N92021D0000475N92021D00005R01 HL105065U19 AG078109RF1 AG069052R01 AG075884RF1 AG079397RF1 AG077386K99 AG082863Mielke MMReiner APManson JENguyen SLi DLaCroix AZMcEvoy LKNievergelt CMMaihofer AXFerrucci LCasanova RShadyab AHNgo LResnick SMLibermann TAZhang BfalsePlasma p-tau217 and incident mild cognitive impairment and dementia in older women: 25-year prospective study in The Women's Health Initiative Memory Study.No study has evaluated whether associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) or dementia vary by race or hormone therapy (HT) use. We examined 2,766 cognitively unimpaired women ≥65 years randomized to HT vs placebo with 25-year follow-up. P-tau217 was associated with incident MCI/dementia (hazard ratio [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 between p-tau217 and dementia were stronger for women randomized to estrogen plus progestin vs placebo (HR, 4.18; 95% CI, 3.41-5.13 vs HR, 3.07; 95% CI, 2.41-3.91, respectively; <i>P</i> interaction=0.044) but did not vary for estrogen alone vs placebo. The combination of p-tau217 and age performed similarly in White and Black women (AUC=72.0% and 70.4%, respectively). Findings show the value of plasma p-tau217 for prediction of MCI and dementia up to 25 years in advance in older women.2025-01-01T00:00:00Z2025 Nov2026-06-03T03:16:38.277Z2026-06-03T03:08:52.422ZS-EPMC126366314128295110.1101/2025.10.30.25339146