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

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.