Bayesian integration of longitudinal and survival outcomes in Alzheimer's disease prediction
Bibliographic record
Abstract
INTRODUCTION: Accurate prediction of Alzheimer's disease (AD) dementia onset and progression to mild cognitive impairment (MCI) is crucial for early intervention and clinical trial design. This study presents a predictive framework leveraging Bayesian model averaging (BMA) with a multivariate functional mixed model (MFMM) to integrate multivariate longitudinal outcomes and survival data. METHODS: The training cohort included 1012 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The validation cohort comprised 2087 participants from the National Alzheimer's Coordinating Center (NACC). BMA methods, including stacking and pseudo-BMA+, aggregated predictions across candidate models to enhance accuracy and robustness. Predictive performance was evaluated using the C-index, a measure of discrimination. RESULTS: Compared to the composite model, BMA improved prediction accuracy. The C-index was 0.777 (stacking) and 0.771 (pseudo-BMA+) in ADNI and 0.743 and 0.738 in NACC. DISCUSSION: This framework offers a robust tool for personalized medicine, enabling accurate predictions and enhanced generalizability across diverse populations. HIGHLIGHTS: We introduced a novel joint modeling framework integrating multivariate longitudinal outcomes (Mini-Mental State Examination and Clinical Dementia Rating Sum of Boxes) with survival data to predict Alzheimer's disease dementia onset and progression. We validated the framework across complementary datasets: Alzheimer's Disease Neuroimaging Initiative (training) and National Alzheimer's Coordinating Center (NACC; validation), with NACC providing a demographically diverse population to assess generalizability. The model enhanced predictive accuracy using Bayesian model averaging, which synthesizes insights across multiple models to reduce uncertainty and improve robustness. The model demonstrated consistent and clinically relevant performance, supporting its applicability for early intervention, precision medicine, and clinical trial design.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".