Abnormal light‐dependent retinal responses in early‐stage Alzheimer's disease
Bibliographic record
Abstract
BACKGROUND: Glia facilitate amyloid beta clearance, which is reduced Alzheimer's disease (ALZ). In a prior optical coherence tomography (OCT) study of the retina, some light-dependent changes co-localized with macroglia, irrespective of neuronal and vascular/avascular boundaries. That putative marker of glial function was subtly abnormal in later stages of Alzheimer's disease (DOI: 10.1016/j.neuroimage.2020.117022). For this study, we (1) hypothesized that the same changes occurred at early stages, before retinal structural changes, (2) explored whether Alzheimer's-associated functional abnormalities varied with proximity to the fovea. METHOD: We compared OCT images from 24 eyes of 13 people at an early stage of biomarker-confirmed Alzheimer's disease ("ALZ") to images from 19 eyes of 10 people without Alzheimer's (biomarker-negative control; "CON"). After measuring macular thicknesses and peripapillary retinal nerve fiber layer thicknesses, we collected functional data - imaging in the darkness versus after bright light exposure. B-scan intensities were transformed into attenuation coefficient maps, which we aligned and spatially normalized to facilitate groupwise comparisons. Multilevel models were used to summarize light-dependent changes in each retinal layer spanning between the fovea and the optic disc. RESULT: ALZ and CON groups well-balanced for age, sex, and education, but had different scores on the Montreal Cognitive Assessment (p <0.05; medians of 21 and 26, respectively). Only one structural difference was noted: the central 1 mm of macula was thicker in ALZ than in CON (296 vs 265 µm; p <0.0005). Both groups showed similar light responses over the rod and cone outer segments, but had significantly different (false discovery rate; q<0.05) functional responses in most other retinal layers; those occupied by macroglia. Group functional differences extended from cone-only foveola through rod-dominated perifovea, and were most robust 0.5-1.0 mm from the foveal center. CONCLUSION: We find robust Alzheimer's-related functional changes in the retina, but in an earlier disease stage than previously reported. The location of those changes implies a macroglial origin, rather than a primarily neural or primarily vascular origin.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.001 | 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".