Multitracer model for staging cortical amyloid deposition using PET imaging
Bibliographic record
Abstract
<h3>Objective</h3> To develop and evaluate a model for staging cortical amyloid deposition using PET with high generalizability. <h3>Methods</h3> Three thousand twenty-seven individuals (1,763 cognitively unimpaired [CU], 658 impaired, 467 with Alzheimer disease [AD] dementia, 111 with non-AD dementia, and 28 with missing diagnosis) from 6 cohorts (European Medical Information Framework for AD, Alzheimer9s and Family, Alzheimer9s Biomarkers in Daily Practice, Amsterdam Dementia Cohort, Open Access Series of Imaging Studies [OASIS]-3, Alzheimer’s Disease Neuroimaging Initiative [ADNI]) who underwent amyloid PET were retrospectively included; 1,049 individuals had follow-up scans. With application of dataset-specific cutoffs to global standard uptake value ratio (SUVr) values from 27 regions, single-tracer and pooled multitracer regional rankings were constructed from the frequency of abnormality across 400 CU individuals (100 per tracer). The pooled multitracer ranking was used to create a staging model consisting of 4 clusters of regions because it displayed a high and consistent correlation with each single-tracer ranking. Relationships between amyloid stage, clinical variables, and longitudinal cognitive decline were investigated. <h3>Results</h3> SUVr abnormality was most frequently observed in cingulate, followed by orbitofrontal, precuneal, and insular cortices and then the associative, temporal, and occipital regions. Abnormal amyloid levels based on binary global SUVr classification were observed in 1.0%, 5.5%, 17.9%, 90.0%, and 100.0% of individuals in stage 0 to 4, respectively. Baseline stage predicted decline in Mini-Mental State Examination (MMSE) score (ADNI: n = 867, <i>F</i> = 67.37, <i>p</i> < 0.001; OASIS: n = 475, <i>F</i> = 9.12, <i>p</i> < 0.001) and faster progression toward an MMSE score ≤25 (ADNI: n = 787, hazard ratio [HR]<sub>stage1</sub> 2.00, HR<sub>stage2</sub> 3.53, HR<sub>stage3</sub> 4.55, HR<sub>stage4</sub> 9.91, <i>p</i> < 0.001; OASIS: n = 469, HR<sub>stage4</sub> 4.80, <i>p</i> < 0.001). <h3>Conclusion</h3> The pooled multitracer staging model successfully classified the level of amyloid burden in >3,000 individuals across cohorts and radiotracers and detects preglobal amyloid burden and distinct risk profiles of cognitive decline within globally amyloid-positive individuals.
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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".