Diagnostic performance of MK and Flortaucipir tau PET for the biological staging of Alzheimer disease
Bibliographic record
Abstract
BACKGROUND: The Alzheimer's Association workgroup criteria (AA-2024) suggest four biological stages based on PET imaging. However, the application of this framework may vary depending on the tau PET tracer used, and the distribution of clinical stages by biological stage may differ. Here, we aim to compare the diagnostic performance of the biological staging of Alzheimer Disease using two different tau PET tracers. METHOD: We analyzed 446 individuals and further stratified 167 Aβ-positive participants from the HEAD study (Longitudinal multicenter head-to-head harmonization of tau PET tracers) that underwent both MK-6240 and Flortaucipir (FTP) tau PET. Four clinical stages (normal, transitional, MCI, and dementia) were defined based on the AA-2024 criteria. Within stage-2 we assessed subgroups: subjective cognitive decline (SCD), subtle objective cognitive decline (SOCD), and mild behavioral impairment (MBI). Logistic and linear models corrected by age and sex tested association of groups with amyloid and tau pathology. The biological staging was performed using tracer-specific thresholds for regional SUVR and testing two regions of interest schemes: (i) proposed by AA-2024 and (ii) Braak stages (Figure 1). Cohen's weighted-kappa (K) statistic measured clinical-biological agreement. Positive predictive value (PPV) of an individual being clinically impaired (MCI or dementia) was calculated for each biological stage. RESULT: Clinical stages showed a progressively increased prevalence of Aβ-positivity and higher entorhinal tau PET pathology from cognitively normal (CN) to SOCD, MCI, and dementia in both tracers. MBI and SCD transitional groups showed no increased Aβ or tau pathology compared to CN (Figure 2). For this reason, only SOCD was considered part of stage 2 for following analyses. All tested biological staging strategies showed moderate agreement (0.34-0.59) with clinical stages using either tracers. The distribution of biological across clinical stages were similar for FTP and MK, with MK-6240 showing lower PPV values in earlier stages than FTP (Table 1). CONCLUSION: Our results support that AA-2024 biological and clinical stages show similar clinical-biological concordance using either Flortaucipir or MK-6240, although this can vary based on methods tested in the study. The MBI and SCD clinical subgroups showed no difference of pathological burden to clinical stage 1, while SOCD transitional stage showed higher burden compared to stage 1.
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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 | 0.009 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| 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".