IC‐P‐140: Baseline clinical scores and volumetric MRI parameters across subjects randomized in mild‐to‐moderate (BMS CN156‐013) and predementia (BMS CN156‐018) Alzheimer's disease clinical trials of avagacestat
Bibliographic record
Abstract
Avagacestat (BMS-708163), an oral gamma-secretase inhibitor, has been studied in two phase 2 clinical trials in mild-to-moderate (CN156-013, completed) and predementia Alzheimer's disease (PDAD) [CN156-018, ongoing]. This post-hoc analysis of MRI volumetric measures from these trials investigates the differences across these study populations and correlations with clinical scores. BMS CN156-013 and CN156-018 AD were conducted in two study groups (n = 209 mild-to-moderate AD subjects with MMSE 16-26, and 263 PDAD subjects with MMSE 24-30. PDAD subjects had objective memory loss (WMS-LM II or FCSRT), CDR-global score of 0.5 and did not meet DSM IV criteria for AD dementia. Furthermore, PDAD subjects had either CSF amyloid-beta 42 levels<200 pg/mL or total tau/amyloid-beta 42 ratio ≥0.39. Volumetric measures were not used as a study inclusion criterion. Hippocampal volume (HCV), brain parenchyma volume (BPV), lateral ventricles volume (LVV) and white-matter lesions volume (WMLV) were calculated from high-resolution T1 and 2D FLAIR images. Population comparison was performed using a two-tailed t-test normalized by intracranial cavity volume (ICV). The partial correlations, controlling age and ICV, were also tested between clinical scores and volumetric measurements. Clinical scores (total MMSE, ADAS-cog, CDR-sb, and ADCS-ADL) were all significantly different between the two study populations (P<0.0001). In PDAD subjects, normalized BPVs were significantly higher while normalized LVV and WMLV were lower. There was no significant difference in HCV between study populations. Significant correlations (r<0.3) were found between all MRI volumetric measures and all clinical scores in an analysis of the combined population. In the PDAD population, BPV was found to be significantly correlated with CDR (r = -0.44) and ADCS-ADL (0.32), and HCV significantly correlated with ADAS-cog (0.38). The randomized study populations of mild-to-moderate AD and PDAD were significantly different in their clinical and whole-brain MRI volumetric measures, but not in their hippocampal volumes. In the analysis of the combined population, the significant correlations between MRI volumes and clinical measures suggested that mild-to-moderate AD and PDAD represent a spectrum of the same disease. Further investigation regarding the utility of MRI as an alternative inclusion criterion to identify PDAD is needed.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".