Data-Driven Analyses of Longitudinal Hippocampal Imaging Trajectories: Discrimination and Biomarker Prediction of Change Classes
Bibliographic record
Abstract
BACKGROUND: Hippocampal atrophy is a well-known biomarker of neurodegeneration, such as that observed in Alzheimer's disease (AD). Although distributions of hippocampal volume trajectories for asymptomatic individuals often reveal substantial heterogeneity, it is unclear whether interpretable trajectory classes can be objectively detected and used for prediction analyses. OBJECTIVE: To detect and predict hippocampal trajectory classes in a computationally competitive context using established AD-related risk factors/biomarkers. METHODS: We used biomarker/risk factor and longitudinal MRI data in asymptomatic adults from the AD Neuroimaging Initiative (n = 351; Mean = 75 years; 48.7% female). First, we applied latent class growth analyses to left (LHC) and right (RHC) hippocampal trajectory distributions to identify distinct classes. Second, using random forest analyses, we tested 38 multi-modal biomarkers/risk factors for their relative importance in discriminating the lower (potentially elevated atrophy risk) from the higher (potentially reduced risk) class. RESULTS: For both LHC and RHC trajectory distribution analyses, we observed three distinct trajectory classes. Three biomarkers/risk factors predicted membership in LHC and RHC lower classes: male sex, higher education, and lower plasma Aβ1-42. Four additional factors selectively predicted membership in the lower LHC class: lower plasma tau and Aβ1-40, higher depressive symptomology, and lower body mass index. CONCLUSION: Data-driven analyses of LHC and RHC trajectories detected three classes underlying the heterogeneous distributions. Machine learning analyses determined three common and four unique biomarkers/risk factors discriminating the higher and lower LHC/RHC classes. Our sequential analytic approach produced evidence that the dynamics of preclinical hippocampal trajectories can be predicted by AD-related biomarkers/risk factors from multiple modalities.
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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 | 0.013 | 0.023 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| 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".