Identifying healthy individuals with Alzheimer’s disease neuroimaging phenotypes in the UK Biobank
Bibliographic record
Abstract
BACKGROUND: Identifying prediagnostic neurodegenerative disease is a critical issue in neurodegenerative disease research, and Alzheimer's disease (AD) in particular, to identify populations suitable for preventive and early disease-modifying trials. Evidence from genetic and other studies suggests the neurodegeneration of Alzheimer's disease measured by brain atrophy starts many years before diagnosis, but it is unclear whether these changes can be used to reliably detect prediagnostic sporadic disease. METHODS: We trained a Bayesian machine learning neural network model to generate a neuroimaging phenotype and AD score representing the probability of AD using structural MRI data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort (cut-off 0.5, AUC 0.92, PPV 0.90, NPV 0.93). We go on to validate the model in an independent real-world dataset of the National Alzheimer's Coordinating Centre (AUC 0.74, PPV 0.65, NPV 0.80) and demonstrate the correlation of the AD-score with cognitive scores in those with an AD-score above 0.5. We then apply the model to a healthy population in the UK Biobank study to identify a cohort at risk for Alzheimer's disease. RESULTS: We show that the cohort with a neuroimaging Alzheimer's phenotype has a cognitive profile in keeping with Alzheimer's disease, with strong evidence for poorer fluid intelligence, and some evidence of poorer numeric memory, reaction time, working memory, and prospective memory. We found some evidence in the AD-score positive cohort for modifiable risk factors of hypertension and smoking. CONCLUSIONS: This approach demonstrates the feasibility of using AI methods to identify a potentially prediagnostic population at high risk for developing sporadic Alzheimer's disease.
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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 | 0.021 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".