Profiling heterogeneity of Alzheimer's disease using white-matter impairment factors
Bibliographic record
Abstract
The clinical presentation of Alzheimer's disease (AD) is not unitary as heterogeneity exists in the disease's clinical and anatomical characteristics. MRI studies have revealed that heterogeneous gray matter atrophy patterns are associated with specific traits of cognitive decline. Although white matter (WM) impairment also contributes to AD pathology, its heterogeneity remains unclear. The Latent Dirichlet Allocation (LDA) method is a suitable framework to study heterogeneity and allows to identify latent impairment factors of AD instead of simply mapping an overall disease effect. By exploring whole brain WM skeleton images by using LDA, three latent factors were revealed in AD: a temporal-frontal impairment factor (temporal and frontal lobes, especially hippocampus and para-hippocampus), a parietal factor (parietal lobe, especially precuneus), and a long fibre bundle factor (corpus callosum and superior longitudinal fasciculus). As revealed by longitudinal analysis, the latent factors have distinct impact on cognitive decline: for executive function (EF), the temporal-frontal factor was more strongly associated with baseline EF compared with the parietal factor, while the long-fibre bundle factor was most associated with decline rate of EF; for memory, the three factors showed almost equal effect on the baseline memory and decline rate. For each participant, LDA estimates his/her composition profile of latent impairment factors, which indicates disease subtype. We also found that the APOE genotype affects the AD subtype. Specifically, APOE ε4 was more associated with the long fibre bundle factor and APOE ε2 was more associated with temporal-frontal factor. By investigating heterogeneity and subtypes of AD through white matter impairment factors, our study could facilitate precision medicine.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".