Digital cognition plus plasma p-Tau217 and Aβ42/40 powerfully predict Alzheimer's progression

Area of Science:

• Neuroscience
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) is pathologically defined by amyloid-β (Aβ) and tau protein accumulation.
• Early identification of individuals with rapid proteinopathy progression is critical for effective intervention and clinical trial design.

Purpose of the Study:

• To identify predictors of rapid amyloid and tau accumulation in Alzheimer's disease.
• To evaluate the efficacy of plasma biomarkers and digital cognitive tests in predicting disease progression and clinical conversion.

Main Methods:

• Longitudinal data from 456 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants were analyzed.
• Amyloid and tau accumulation rates were quantified using PET imaging and linear mixed-effects models.
• Predictors of accumulation and conversion were assessed using logistic and Cox regression, incorporating demographics, cognitive measures, and plasma biomarkers (p-tau217, Aβ42/Aβ40).

Main Results:

• Plasma p-tau217 and Aβ42/Aβ40 levels significantly predicted rapid amyloid and tau accumulation and clinical conversion.
• Plasma p-tau217 was the strongest predictor (odds ratio up to 6.6).
• Digital cognitive measures demonstrated high predictive accuracy (AUC up to 0.92), comparable or superior to traditional tests.

Conclusions:

• Plasma p-tau217 and Aβ42/Aβ40 are robust biomarkers for predicting Alzheimer's disease progression.
• Cognitive measures, particularly digital assessments, significantly support the prediction of disease trajectory.