Data-driven approaches for Tau-PET imaging biomarkers in Alzheimer’s disease
Bibliographic record
Abstract
ABSTRACT Previous positron emission tomography (PET) studies have quantified filamentous tau pathology using regions-of-interest (ROIs) based on observations of the topographical distribution of neurofibrillary tangles in post-mortem tissue. However, such approaches may not take full advantage of information contained in neuroimaging data. The present study employs an unsupervised data-driven method to identify spatial patterns of tau-PET distribution, and to compare these patterns to previously published “pathology-driven” ROIs. Tau-PET patterns were identified from a discovery sample comprised of 123 normal controls and patients with mild cognitive impairment or Alzheimer’s disease (AD) dementia from the Swedish BioFINDER cohort, who underwent [ 18 F]AV1451 PET scanning. Associations with cognition were tested in a separate sample of 90 individuals from ADNI. BioFINDER [ 18 F]AV1451 images were entered into a robust voxelwise stable clustering algorithm, which resulted in five clusters. Mean [ 18 F]AV1451 uptake in the data-driven clusters, and in 35 previously published pathology-driven ROIs, was extracted from ADNI [ 18 F]AV1451 scans. We performed linear models comparing [ 18 F]AV1451 signal across all 40 ROIs to several tests of global cognition, adjusting for age, sex and education. Two data-driven ROIs consistently demonstrated the strongest or near-strongest effect sizes across all cognitive tests. Inputting all regions plus demographics into a feature selection routine resulted in selection of two ROIs (one data-driven, one pathology-driven) and education, which together explained 28% of the variance of a global cognitive composite score. Our findings suggest that [ 18 F]AV1451-PET data naturally clusters into spatial patterns that are biologically meaningful and that may offer advantages as clinical tools.
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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 | 0.017 | 0.034 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.005 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".