Clinical utility of combined amyloid biomarkers in early cognitive impairment

BackgroundEarly etiological diagnosis of cognitive impairment is challenging. Amyloid PET improves diagnostic accuracy but is costly and limited in availability. Plasma phosphorylated tau-217 (p-tau217) has emerged as a scalable, minimally invasive biomarker.ObjectiveThis study aimed to evaluate the diagnostic and prognostic utility of amyloid PET and plasma p-tau217 in older adults with early cognitive impairment.MethodsWe prospectively enrolled 100 adults aged ≥ 65 years with mild cognitive impairment or mild dementia. Participants underwent comprehensive clinical evaluation, brain MRI, ¹⁸F-florbetaben amyloid PET, and plasma p-tau217 analysis. Longitudinal cognitive decline was assessed over a median follow-up of 1.3 years.ResultsAmyloid PET was positive in 45% and resulted in diagnostic revision in 39%. Plasma p-tau217 levels were significantly higher in amyloid-positive individuals (1.178 ± 0.652 versus 0.642 ± 0.940 pg/mL, p < 0.001) and accurately identified amyloid positivity (AUC = 0.855). Both amyloid PET positivity (HR = 6.61, 95% CI 2.36-18.50; p < 0.001) and elevated p-tau217 (HR = 4.43, 95% CI 1.83-10.68; p = 0.001) independently predicted faster cognitive decline. Combined biomarker analysis revealed a stepwise risk stratification, with dual-positive individuals showing the most rapid deterioration (global p < 0.001). Among amyloid-positive patients, elevated p-tau217 further distinguished those with faster progression (p = 0.035).ConclusionsAmyloid PET and plasma p-tau217 provide complementary diagnostic and prognostic value. While PET refines etiological diagnosis, p-tau217 serves as a robust predictor of amyloid status and cognitive trajectory. Integrating these biomarkers improves risk stratification and may facilitate patient selection for disease-modifying therapies.