Imaging‐based biological staging associates with brain atrophy in preclinical Alzheimer's disease
Bibliographic record
Abstract
Abstract Background Alzheimer's disease (AD) diagnostic and staging criteria rely on imaging biomarkers as robust tools for in vivo disease assessment. Among these, cortical brain atrophy is recognized as a key hallmark of disease progression. However, rates of cortical atrophy in preclinical stages remain insufficiently explored within current staging frameworks. In a group of amyloid β‐positive (Aβ+) asymptomatic individuals, we investigated the association of the imaging‐based biological AD staging framework with longitudinal brain atrophy patterns. Methods We included 162 Aβ+ participants from the A4 Study placebo group with available magnetic resonance imaging (MRI) and positron emission tomography (PET) for amyloid‐β (Aβ) plaques ([ 18 F]Florbetapir) and tau ([ 18 F]Flortaucipir) at baseline, along with a follow‐up MRI at least 2 years after baseline. Tau positivity in the medial temporal lobe (T MTL +) and in the neocortex (T NEO +) were determined as tau PET standardized uptake value ratio (SUVR) of 2.5 standard deviations above the mean derived from a separate population (LEARN substudy) of 55 Aβ‐negative individuals. Groups were compared using analysis of covariance (ANCOVA) with Tukey's multiple comparison test, adjusting for relevant covariates. Results Demographic characteristics of the population are displayed in Table 1. In cross‐sectional analysis, we observed that baseline cortical gray matter volumes differed significantly only between A+T NEO + and A+T− groups ( p = 0.042), with no significant differences between other groups ( p >0.05 for both; Figure 1a). Longitudinally, A+T NEO + individuals exhibited greater rates of cortical atrophy compared to A+T− ( p <0.001) and A+T MTL + ( p = 0.007), along with A+T MTL + individuals showing higher rates of cortical atrophy compared to the A+T− group ( p = 0.042; Figure 1b). Subsequent regional analyses revealed that the A+T NEO + individuals showed higher atrophy compared to both A+T− and A+T MTL + in temporal and parietal regions (Figure 2). Conclusions Our findings reveal that the imaging‐based biological AD staging is closely associated with cortical brain atrophy, showing a gradual acceleration in rates of cortical atrophy across stages. Additionally, our results suggest that serial volumetric measurements of temporoparietal brain regions may be sensitive biomarkers of early disease progression. Taken together, our findings provide valuable insights for applying the imaging‐based biological AD staging in preclinical AD.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".