O4‐12‐04: CEREBROSPINAL FLUID AND PET MEASURES OF TAU PATHOLOGY INDICATE A DIFFERENT STATE OF AD PATHOPHYSIOLOGICAL PROGRESSION
Bibliographic record
Abstract
Alzheimer's disease-(AD) related pathological changes are thought to occur decades prior to cognitive impairment. It was recently suggested that discrepancy between CSF and PET measures of amyloid-beta (Aβ) reflects timing of disease processes. We sought to assess whether similar observations were true for measures tau pathology. One-hundred seventeen non-demented participants (62 Healthy and 55 with Mild cognitive impairment) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) had available CSF and PET (flortaucipir) measures of tau pathology within a 24-month interval. Using a data-driven, clinically relevant threshold for CSF P-tau (≥26.64 pg/mL) and a literature-based cut-off for entorhinal flortaucipir (SUVR≥1.3), we categorized individuals into four groups (CSF-/PET-; CSF+/PET-; CSF-/PET+ and CSF+/PET+). We then compared these groups on demographic/clinical variables, global Aβ-PET (AV-45) burden and tau-PET binding across all Braak stage ROIs. Finally, we assessed group differences in P-tau rates of accumulation in the years prior to flortaucipir scanning. Among all participants, 72 were CSF-/PET-, 18 were CSF+/PET-, 22 were CSF+/PET+, and only 6 were CSF-/PET+ (Table 1, Figure 1). Given the reduced inference from the CSF-/PET+ group, we did not consider it in our main analysis. All groups had comparable age, education years and sex ratios. There was an increase in Aβ-PET burden when comparing CSF-/PET-, CSF+/PET- and CSF+/PET+ individuals (Figure 2). CSF-/PET- and CSF+/PET- participants had comparable executive functioning, memory performance and a similar frequency of APOE ε4 carriers. When compared to both PET- groups, CSF+/PET+ individuals had worse cognitive and executive functioning performance (all P < 0.001). CSF+/PET- participants did not show any hints of elevated flortaucipir binding in Braak stage I-VI ROIs or at a single Desikan-Killiany atlas ROI level when compared to CSF-/PET- individuals. However, both CSF+ participant groups had faster retrospective rates of CSF P-tau accrual than CSF- participants (Figure 3).
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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 | 0.001 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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".