Bayesian Nonparametric Causal Inference for Quantile Residual Life: An Application to Alzheimer's Disease

TL;DR

This paper develops a Bayesian nonparametric method to estimate causal effects on remaining dementia-free time in Alzheimer's research, addressing confounding and heavy censoring.

Contribution

It introduces a novel Bayesian enriched Dirichlet process mixture model for joint distribution estimation and causal inference in survival analysis with censored data.

Findings

Elevated baseline amyloid correlates with shorter remaining dementia-free time.

The method performs well under complex heterogeneity and heavy censoring in simulations.

Application to ADNI data reveals amyloid status impacts prognosis across subgroups.

Abstract

In Alzheimer's disease research, for individuals who remain dementia-free through a given follow-up time, an important clinical question is how much longer they are likely to remain dementia-free. Quantiles of this remaining time provide clinically interpretable prognostic milestones and can help characterize prognostic heterogeneity across baseline groups. We address this question in the Alzheimer's Disease Neuroimaging Initiative (ADNI), focusing on baseline amyloid status as the exposure. Estimation is challenging because amyloid status is observed rather than randomized, requiring adjustment for confounding, and because time to dementia onset is heterogeneous and heavily right-censored. We estimate causal contrasts in quantile residual life using a Bayesian nonparametric enriched Dirichlet process mixture model for the joint distribution of event times, exposure, and baseline covariates, with inference via Bayesian g-computation. The approach accommodates ignorable missing baseline covariates through data augmentation, supports inference across clinically relevant landmark times, and allows sensitivity analysis for residual unmeasured confounding. Simulation studies show good performance under complex heterogeneity and heavy censoring. In ADNI, elevated baseline amyloid was associated with shorter quantiles of remaining dementia-free time than non-elevated baseline amyloid among individuals who remained dementia-free through relevant landmark times, overall and within baseline diagnostic subgroups.