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Plasma p-tau217 and incident mild cognitive impairment and dementia in older women: 25-year prospective study in The Women's Health Initiative Memory Study.


ABSTRACT: 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; P 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.

SUBMITTER: Shadyab AH 

PROVIDER: S-EPMC12636631 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature

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Plasma p-tau217 and incident mild cognitive impairment and dementia in older women: 25-year prospective study in The Women's Health Initiative Memory Study.

Shadyab Aladdin H AH   Zhang Bowei B   LaCroix Andrea Z AZ   Mielke Michelle M MM   Resnick Susan M SM   Nguyen Steve S   Ferrucci Luigi L   Libermann Towia A TA   Ngo Long L   Casanova Ramon R   Reiner Alexander P AP   Li Danni D   Nievergelt Caroline M CM   Maihofer Adam X AX   Manson JoAnn E JE   McEvoy Linda K LK  

medRxiv : the preprint server for health sciences 20251111


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  ...[more]

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