Retinal AD Biomarkers in Cognitively Unimpaired Older Adults
Bibliographic record
Abstract
Abstract Background The retina is a novel biomarker target for examining AD pathology, specifically beta‐amyloid (Aβ). Though relationship between retinal Aβ and standard preclinical AD biomarkers (cerebral Aβ PET) remains understudied, retinal inclusion bodies (IB, strongly hypothesized to contain fibrillar Aβ), predict cerebral Aβ load in the anterior cingulate cortex (ACC). This study explored the value of retinal IB as a preclinical AD biomarker, comparing number and surface area (SA) of IB with cerebral Aβ PET. Method 36 older adults aged 55‐80 were identified as cognitively unimpaired based on Clinical Dementia Rating Scale (CDR) of 0 and a score ≥24 on the Montreal Cognitive Assessment (MoCA). PET status (20 Aβ+, 16 Aβ‐) was available through prior studies. Retinal IB data was captured on Heidelberg SPECTRALIS using blue light fundus autofluorescence. Number and surface area of IB were computed manually by two qualified raters. Inter‐rater reliability was measured with Cohen’s Kappa. Binomial logistic regression and ROC assessed the accuracy, sensitivity, and specificity of retinal IB in predicting Aβ PET status (positive vs. negative). Result Inter‐rater reliability was high (Cohens kappa =0.9). Mann Whitney U Tests showed no significant group differences in the number (U=156.5, p=.906) and SA of IB (U=156.5, p=.962) between the Aβ+ and Aβ‐ PET groups. Binomial logistic regression including predictors (APOE status, age, MoCA score, and SA of IB), showed that SA of IB accurately predicted PET status 61.1% of the time, (sensitivity 75%, specificity 43.8%, AUC =.408). The analysis was repeated with the number of IB, showing that PET status was correctly predicted 63.9% of the time (sensitivity 85%, specificity 37.5%, AUC=.448). Conclusion Retinal IB, strongly hypothesized to contain fibrillar Aβ, were not strongly predictive of Aβ PET status in this sample. Given the sample characteristics, the results align with what we hypothesized. Further longitudinal analysis with larger sample sizes and PET centiloid readings in regions of early cerebral Aβ accumulation could help determine the value of retinal imaging as a risk biomarker in preclinical AD.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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 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".