Identifying individuals with Alzheimer's disease‐like brains based on structural imaging in the Human Connectome Project Aging cohort
Bibliographic record
Abstract
Given the difficulty in factoring out typical age effects from subtle Alzheimer's disease (AD) effects on brain structure, identification of very early, as well as younger preclinical "at-risk" individuals has unique challenges. We examined whether age-correction procedures could be used to better identify individuals at very early potential risk from adults who did not have any existing cognitive diagnosis. First, we obtained cross-sectional age effects for each structural feature using data from a selected portion of the Human Connectome Project Aging (HCP-A) cohort. After age detrending, we weighted AD structural deterioration with patterns quantified from data of the Alzheimer's Disease Neuroimaging Initiative. Support vector machine was then used to classify individuals with brains that most resembled atrophy in AD across the entire HCP-A sample. Additionally, we iteratively adjusted the pipeline by removing individuals classified as AD-like from the HCP-A cohort to minimize atypical brain structural contributions to the age detrending. The classifier had a mean cross-validation accuracy of 94.0% for AD recognition. It also could identify mild cognitive impairment with more severe AD-specific biomarkers and worse cognition. In an independent HCP-A cohort, 8.8% were identified as AD-like, and they trended toward worse cognition. An "AD risk" score derived from the machine learning models also significantly correlated with cognition. This work provides a proof of concept for the potential to use structural brain imaging to identify asymptomatic individuals at young ages who show structural brain patterns similar to AD and are potentially at risk for a future clinical disorder.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".