Imaging‐based Biological Staging for Alzheimer's Disease Prognosis
Bibliographic record
Abstract
Abstract Background Recent revised criteria for Alzheimer's disease (AD) emphasize the potential utility of imaging biomarkers in disease staging. Although promising, the practical applicability of staging schemes requires further investigation. In this study, amyloid‐β (Aβ) and tau positron emission tomography (PET) were used to evaluate the prognostic performance of the imaging‐based biological staging criteria in cognitively unimpaired (CU) individuals. Method This longitudinal analysis involved 662 CU individuals: 467 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort and 195 individuals from the Anti‐Amyloid Treatment in Asymptomatic AD (A4) study placebo group. In the ADNI cohort, Aβ positivity (A+) was defined as standardized uptake value ratios (SUVR) >1.11 for [18F]Florbetapir and >1.08 for [18F]Florbetaben. In A4, Aβ positivity was established via visual reading. Tau tangles were assessed using [18F]Flortaucipir for both cohorts, with positivity defined as 2.0 standard deviations (SD) above the mean SUVR of Aβ‐negative CU reference groups (ADNI: n = 352; LEARN A4 substudy: n = 55). These tau PET cutoffs, derived from the medial temporal lobe (MTL) and neocortex (NEO) regions, were applied to classify individuals as T MTL + and T NEO +. We used Kaplan‐Meier curves and Cox proportional hazard models to evaluate the 4‐year risk of clinical progression (i.e., one point increase in the Clinical Dementia Rating ‐ Sum of Boxes) according to imaging‐based baseline groups. Result The mean (SD) age of the study population was 72.1 (6.8) years, and 264 (39.9%) were men (Table 1). Kaplan‐Meier curves demonstrated that the A+T NEO + group presented a separate survival probability curve compared to the other groups (Figure 1A). Cox proportional‐hazards models corroborated the greatest risk of clinical progression in the A+T NEO + (HR = 9.98) group, followed by the A+T MTL + (HR = 4.29) and A+T‐ (HR = 2.31) groups, in comparison to the reference group (A‐T‐; Figure 1B). Conclusion The integration of Aβ and tau PET imaging provides critical prognostic information in early disease stages, with neocortical tau deposition performing as a robust predictor of clinical progression. These findings reinforce the utility of imaging biomarkers for AD staging and prognosis, highlighting that the topography of tau tangle accumulation is a key factor in enhancing risk stratification of individuals with 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 | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".