Mind the Gap: Does Brain Age Improve Alzheimer’s Disease Prediction?
Bibliographic record
Abstract
Brain age is widely regarded as a powerful marker of general brain health. Brain age models are typically trained on large datasets to predict chronological age, which may offer advantages in predicting specific health outcomes, much like the success of finetuning large language models for specific applications. However, it is also well accepted that machine learning models trained to directly predict specific outcomes (i.e., direct models) often outperform those trained on surrogate objectives. Therefore, despite their much larger training data, it is unclear whether brain age models outperform direct models in predicting specific brain health outcomes. Here, we compare large-scale brain age models (pretrained on 53,542 participants) and direct models for predicting specific health outcomes related to Alzheimer's disease (AD) dementia. Using anatomical T1 scans from three continents (N = 1,848), we find that summarizing brain age with a single scalar (i.e., brain age gap) led to poor prediction performance. Using higher-dimensional intermediate representations of brain age models led to better prediction, but was still worse than direct models without finetuning. Using intermediate representations of finetuned brain age models was necessary to achieve similar performance to direct models. Overall, our results do not discount brain age as a useful marker of general brain health but suggest that using chronological age as a pretraining target might be suboptimal for predicting specific health outcomes.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.001 | 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 teacher head, 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".