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Multimodal Retinal Imaging for the Detection of Early Alzheimer’s Disease: Combining Biochemical, Structural, and Vascular Biomarkers
Ghesquiere M, Christinaki E, Lemmens S, Van Eijgen J, Beeckmans L, Ghinis A, Jacobs T, Keer KV et al.. Preprints.org, 2026-08-17
Topic: Plasma and spinal-fluid biomarkers
Plain-language summary
Alzheimer’s disease (AD) pathology is increasingly recognized to manifest in the retina, offering a non-invasive window for early biomarker discovery. This proof-of-concept study investigated whether multimodal retinal imaging—hyperspectral imaging (HSI), optical coherence tomography (OCT), and color fundus photography (CFP)—can differentiate individuals with and without cerebral amyloid-beta (Aβ) pathology in 40 participants with PET-confirmed Aβ status (17 Aβ+, cognitively normal or with mild cognitive impairment; 23 Aβ− cognitively normal controls). HSI-derived gray-level co-occurrence matrix (GLCM) texture, OCT-derived ganglion cell–inner plexiform layer (GC-IPL) thickness, and CFP-derived vascular biomarkers (VBMs) were extracted, and logistic regression with leave-one-out cross-validation assessed classification performance per modality, alone and combined; the cohort was supplemented with AD dementia patients for exploratory trajectory analyses. HSI showed significantly lower GLCM correlation at 466 nm in Aβ+ participants, most pronounced in the inferior macula (p = 0.01, AUC = 0.72), and GC-IPL thickness confirmed an “inferior vulnerability zone.” Combining HSI and GC-IPL features yielded the best performance (AUC = 0.84; sensitivity = 0.82; specificity = 0.78), whereas vascular biomarkers contributed minimally. HSI features followed a non-monotonic trajectory across the AD continuum, decreasing in early Aβ+ stages and rising again in dementia. These findings demonstrate synergy between HSI and OCT for detecting retinal biomarkers of early-stage AD, supporting multimodal retinal imaging as a scalable screening approach warranting validation in larger, longitudinal cohorts.
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APA 7th
Ghesquiere, M., Christinaki, E., Lemmens, S., Van Eijgen, J., Beeckmans, L., Ghinis, A., et al. (2026). Multimodal Retinal Imaging for the Detection of Early Alzheimer’s Disease: Combining Biochemical, Structural, and Vascular Biomarkers. Preprints.org. https://doi.org/10.20944/preprints202608.1118.v1
Vancouver
Ghesquiere M, Christinaki E, Lemmens S, Van Eijgen J, Beeckmans L, Ghinis A, et al. Multimodal Retinal Imaging for the Detection of Early Alzheimer’s Disease: Combining Biochemical, Structural, and Vascular Biomarkers. Preprints.org. 2026. doi:10.20944/preprints202608.1118.v1.
BibTeX
@article{ghesquiere2026-47400e3d,
author = {Ghesquiere, M. and Christinaki, E. and Lemmens, S. and Van Eijgen, J. and Beeckmans, L. and Ghinis, A. and Jacobs, T. and Keer, K. V. and others},
title = {{Multimodal Retinal Imaging for the Detection of Early Alzheimer’s Disease: Combining Biochemical, Structural, and Vascular Biomarkers}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202608.1118.v1},
url = {https://doi.org/10.20944/preprints202608.1118.v1}
}
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Key findings
- HSI showed significantly lower GLCM correlation at 466 nm in Aβ+ participants, most pronounced in the inferior macula (p = 0.01, AUC = 0.72), and GC-IPL thickness confirmed an “inferior vulnerability zone.” Combining HSI and GC-IPL features yielded the best performance (AUC = 0.84; sensitivity = 0.82; specificity = 0.78), whereas vascular biomarkers contributed minimally.
- These findings demonstrate synergy between HSI and OCT for detecting retinal biomarkers of early-stage AD, supporting multimodal retinal imaging as a scalable screening approach warranting validation in larger, longitudinal cohorts.
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Study details
- Study designlongitudinal study
- Participants40
- Effect sizeAUC = 0.72; AUC = 0.84
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 47 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 29 of the 62 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 40 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 29 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 29 of the 62 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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