This longitudinal pooled cohort study evaluated whether baseline plasma p-tau217 levels predict progression to cognitive impairment (MCI, dementia, or CDR ≥0.5) and rate of cognitive decline in 2,684 cognitively unimpaired older adults across 6 cohorts in North America, Japan, and Australia, followed for a median of 5.4 years (max 13.5 years).
Each 1-SD rise in plasma p-tau217 increased risk of cognitive impairment (HR 1.38, 95% CI 1.30–1.46; HR 1.32 after amyloid PET adjustment). Over 5 years, participants with very high p-tau217 (>2.5 SD) had a 38% absolute risk of progression (vs. ~24% in the high group) and showed faster cognitive decline (–0.07 vs. +0.03 latent PACC units/year in the low group).
- Cohorts were selected (not general population), limiting generalizability to unselected individuals. - Long-term (10-year) risk estimates were constrained by limited data at extended follow-up. - P-tau217 assays were not fully harmonized across cohorts, which may introduce variability.
Plasma p-tau217 provides meaningful, quantifiable absolute risk estimates for cognitive decline in cognitively unimpaired older adults — a very high level confers roughly 38% risk of progression within 5 years. Clinicians and trial designers can use these thresholds to stratify patients, though validation in unselected community populations is still needed before applying this to routine individual prognosis.
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