Plasma p-tau217 and NfL predict incident dementia in the community

INTRODUCTION: Characterizing the prognostic utility of blood-based biomarkers for Alzheimer's disease (AD) in predicting longitudinal cognitive trajectories is essential; however, population-based evidence is needed. METHODS: We evaluated plasma phosphorylated tau at threonine 217 (p-tau217) and plasma neurofilament light chain (NfL) in 4,971 dementia-free individuals aged 70 years and older from the population-based Norwegian HUNT study. Predefined cut offs categorized biomarker ranges (p-tau217: low, intermediate, high; NfL: low, high), in addition to continuous biomarker analysis. RESULTS: Adjusted for other risk factors, higher baseline p-tau217 and NfL ranges indicated a significantly increased dementia risk after four years compared to low ranges (intermediate p-tau217: risk ratio [RR] 1.23, 95% CI 1.01-1.50; high p-tau217: RR 2.05, 95% CI 1.73-2.44; high NfL: RR 1.72, 95% CI 1.31-2.27; jointly high p-tau217 and NfL: RR 3.32, 95% CI 2.61-4.23). The estimated cumulative risk of all-cause dementia was 10.6% (95% CI 9.3-12.1) for low p-tau217, 16.9% (95% CI 14.6-19.5) for intermediate p-tau217, 33.0% (95% CI 29.9-36.1) for high p-tau217, 15.7% (95% CI 14.4-17.0) for low NfL, 35.4% (95% CI 30.6-40.5) for high NfL, and 47.8% (95% CI 40.7-55.0) for jointly high p-tau217 and NfL. The association of p-tau217 with incident dementia differed by sex. DISCUSSION: These findings support the use of blood-based biomarkers for population-level dementia risk stratification, underscore the value of combining markers to improve prognostic precision, and can aid clinicians using plasma p-tau217 or NfL in interpreting dementia risk.