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Published in: Alzheimer's Research & Therapy 1/2023

Open Access 01-12-2023 | Alzheimer's Disease | Research

Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer’s disease

Authors: Edmund Arthur, Swetha Ravichandran, Peter J. Snyder, Jessica Alber, Jennifer Strenger, Ava K. Bittner, Rima Khankan, Stephanie L. Adams, Nicole M. Putnam, Karin R. Lypka, Juan A. Piantino, Stuart Sinoff

Published in: Alzheimer's Research & Therapy | Issue 1/2023

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Abstract

Background

Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer’s disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs. We hypothesized the mid-peripheral CFZs will be enlarged in CU older adults at high risk for AD compared to low-risk individuals.

Methods

20 × 20° optical coherence tomography angiography images consisting of 512 b-scans, 512 A-scans per b-scan, 12-µm spacing between b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea of 57 eyes of 37 CU low-risk (mean age: 66 years) and 50 eyes of 38 CU high-risk older adults (mean age: 64 years; p = 0.24) were involved in this study. High-risk participants were defined as having at least one APOE e4 allele and a positive first-degree family history of AD while low-risk participants had neither of the two criteria. All participants had Montreal Cognitive Assessment scores ≥ 26. The mid-peripheral CFZs were computed in MATLAB and compared between the two groups.

Results

The periarteriole CFZ of the high-risk group (75.8 ± 9.19 µm) was significantly larger than that of the low-risk group (71.3 ± 7.07 µm), p = 0.005, Cohen’s d = 0.55. The perivenule CFZ of the high-risk group (60.4 ± 8.55 µm) was also significantly larger than that of the low-risk group (57.3 ± 6.40 µm), p = 0.034, Cohen’s d = 0.42. There were no significant differences in foveal avascular zone (FAZ) size, FAZ effective diameter, and vessel density between the two groups, all p > 0.05.

Conclusions

Our results show larger mid-peripheral CFZs in CU older adults at high risk for AD, with the potential for the periarteriole CFZ to serve as a novel retinal vascular biomarker for early AD risk detection.
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Metadata
Title
Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer’s disease
Authors
Edmund Arthur
Swetha Ravichandran
Peter J. Snyder
Jessica Alber
Jennifer Strenger
Ava K. Bittner
Rima Khankan
Stephanie L. Adams
Nicole M. Putnam
Karin R. Lypka
Juan A. Piantino
Stuart Sinoff
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-023-01312-8

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