Predicting clinical progression trajectories of early Alzheimer's disease patients

Abstract

Background: Models for forecasting individual clinical progression trajectories in early Alzheimer's disease (AD) are needed for optimizing clinical studies and patient monitoring.

Methods: Prediction models were constructed using a clinical trial training cohort (TC; n = 934) via a gradient boosting algorithm and then evaluated in two validation cohorts (VC 1, n = 235; VC 2, n = 421). Model inputs included baseline clinical features (cognitive function assessments, APOE ε4 status, and demographics) and brain magnetic resonance imaging (MRI) measures.

Results: The model using clinical features achieved R² of 0.21 and 0.31 for predicting 2-year cognitive decline in VC 1 and VC 2, respectively. Adding MRI features improved the R² to 0.29 in VC 1, which employed the same preprocessing pipeline as the TC. Utilizing these model-based predictions for clinical trial enrichment reduced the required sample size by 20% to 49%.

Discussion: Our validated prediction models enable baseline prediction of clinical progression trajectories in early AD, benefiting clinical trial enrichment and various applications.

Trial registration: ClinicalTrials.gov NCT02956486 NCT03036280 NCT01767311.

Keywords: clinical trial enrichment; disease progression; machine learning; mild cognitive impairment; prognosis.