F1‐03‐01: Potential of ad biomarkers to reveal the presymptomatic disease process and the effects of treatments that may retard it
Bibliographic record
Abstract
The evolution of AD spans some 30 years, over much of which time symptoms are absent. This lack of available symptomatic endpoints is a fundamental problem for prevention research. Disease progression may be revealed, however, by various biomarkers that change over time. Preventive interventions can retard or halt this progression of pre-symptomatic disease (and its markers) thereby deferring the later onset of symptoms. In theory, therefore, pre-symptomatic biomarker trajectories can be used to select individuals for prevention trials and to identify preventive treatments with preliminary evidence in favor of their probable efficacy. Several issues confront longitudinal biomarker studies as indicators of pre-symptomatic disease progression: 1) we need validation of biomarker trajectories as true indicators of pathogenesis, i.e., of subsequent symptom onset; 2) we must identify which individual biomarkers are best suited to this purpose at various stages of disease development; and 3) we need analytic methods that can encompass the multiple metrics employed to reflect the disease progress while avoiding difficulties with multiple comparisons. Successful example applications of this approach will help demonstrate its value. We present data from the BIOCARD and Canadian PREVENT-AD studies, two programs that are currently characterizing the progression of biomarkers in persons at high risk of AD dementia. BIOCARD enrolled 349 cognitively normal persons at baseline and has obtained serial cerebrospinal fluid (CSF), neuroimaging and cognitive measures markers for up to 18 years. The study is examining (validating) these markers, either alone or combination, as predictors of subsequent symptom onset. PREVENT-AD has up to two years of biomarker data from 241 individuals with a parental history of AD. It assesses sensorineural abilities (olfaction, central auditory processing) as well as CSF and advanced neuroimaging markers as indicators of pre-symptomatic AD progression. It also includes a nested randomized, placebo-controlled biomarker-endpoint trial to assess effects of naproxen on the trajectory of such changes. Both BIOCARD and PREVENT-AD are evaluating analytic methods that can interpret multiple biomarker results as indicators of disease progress toward subsequent symptom onset. The talks that follow will describe the two studies' progress in pre-symptomatic biomarker research toward improving the selection of participants and promising interventions for prevention trials.
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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 | 0.012 | 0.016 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.029 | 0.006 |
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".