Exploring the potential impact of multi-factor precision interventions in Alzheimer’s disease with system dynamics
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Numerous clinical trials based on a single-cause paradigm have not resulted in efficacious treatments for Alzheimer's disease (AD). Recently, prevention trials that simultaneously intervened on multiple risk factors have shown mixed results, suggesting that careful design is necessary. Moreover, intensive pilot precision medicine (PM) trial results have been promising but may not generalize to a broader population. These observations suggest that a model-based approach to multi-factor precision medicine (PM) is warranted. We systematically developed a system dynamics model (SDM) of AD for PM using data from two longitudinal studies (N=3660). This method involved a model selection procedure in identifying interaction terms between the SDM components and estimating individualized parameters. We used the SDM to explore simulated single- and double-factor interventions on 14 modifiable risk factors. We quantified the potential impact of double-factor interventions over single-factor interventions as 1.5 [95% CI: 1.5-2.6] and of SDM-based PM over a one-size-fits-all approach as 3.5 [3.1, 3.8] ADAS-cog-13 points in 12 years. Although the model remains to be validated, we tentatively conclude that multi-factor PM could come to play an important role in AD prevention.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it