Assessment of Association of Tau PET Spatial Patterns with Cognitive Domains in Participants with Early Alzheimer's Disease in the Phase 2 Auτonomy Trial
Bibliographic record
Abstract
BACKGROUND: Posdinemab is an anti-phosphorylated tau monoclonal antibody currently under investigation in early Alzheimer's disease (AD). The phase-2 Auτonomy trial (NCT04619420) enrolled participants with mild cognitive impairment (MCI) or mild AD dementia (Clinical Dementia Rating-Global Score [CDR GS] 0.5/memory box ≥0.5) with intermediate levels of tau, pre-screened using a Janssen p217+tau plasma assay and confirmed with tau Positron Emission Tomography (PET). Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) indices representing five cognitive domains were analyzed for voxelwise associations with tau PET. A brain wide map was reconstructed that reveals associations between cognitive domains and tau pathology. METHOD: F-MK-6240 Standardized Uptake Value Ratio (SUVR; cerebellar gray reference region). SUVR volumes were non-linearly aligned to Montreal Neurological Institute space and smoothed within a gray matter mask to a Full Width at Half Max of 12 mm. Associations with each cognitive domain were computed using Spearman rank to minimize outlier effect. For each of the 5 correlation volumes, voxel values were transformed to their rank. Finally, a domain preference map was generated by assigning to each voxel the highest ranked of the 5 domains and its corresponding Spearman correlation to enable statistical thresholding. RESULT: , False Discovery Rate q<0.01) across most of the brain for all, but the visuospatial domain, for which significant correlations were largely in right occipital cortex. The following domain associations were observed (Figure): Visuospatial to right occipital cortex, with trends of association in left occipital cortex; Language to left temporal, supramarginal, and inferior parietal; Delayed-memory to inferior temporal, fusiform, anterior cingulate, insula, and hippocampus; Attention to left middle occipital, precuneus, and bilateral frontal; Immediate-memory to bilateral middle and superior frontal, precuneus and middle temporal. CONCLUSION: In participants with intermediate tau and early AD, randomized in the Auτonomy trial, we map using a spatially unbiased analysis of tau PET, which cognitive domains are relatively most impacted by tau pathology across the brain. The ensuing maps reflect established brain functional organization. These findings demonstrate close association between presence/location of tangles and cognitive profile.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".