Evidence map›Paper›PMID 37828548›Full record

ArticleAlzheimer's research & therapy2023

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

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 and 2 more

Open access · goldAbstract read
In one paragraph

Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Association and Multimodal Model of Retinal Mid-Peripheral Capillary Free Zones with Structural and Functional Parameters in Diabetic Patients Without Clinical Retinopathy.Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Cerebral Amyloid Deposition WithHuman brain mapping · 2025
    Article
  7. Article
  8. Article
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  10. Article
  11. Alzheimer's disease pathophysiology in the Retina.Progress in retinal and eye research · 2024
    Review
  12. Quantifying Putative Retinal Gliosis in Preclinical Alzheimer's Disease.Investigative ophthalmology & visual science · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 10 institutions in 1 country.

Edmund Arthur *School of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA. earthur@uab.edu.
Swetha Ravichandran *School of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA.
Peter J SnyderDepartment of Neurology, Alpert Medical School of Brown University, Providence, RI, USA.
Jessica AlberDepartment of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
Jennifer StrengerButler Hospital Memory & Aging Program, Providence, RI, USA.
Ava K BittnerDepartment of Ophthalmology, Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
Rima KhankanSouthern California College of Optometry, Marshall B. Ketchum University, Fullerton, CA, USA.
Stephanie L AdamsIllinois College of Optometry, Chicago, IL, USA.
Nicole M PutnamState University of New York College of Optometry, New York, NY, USA.
Karin R LypkaBascom Palmer Eye Institute, University of Miami, Miami, FL, USA.
Juan A PiantinoDepartment of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
Stuart SinoffProvidence-Swedish Health System, Seattle, WA, USA.
University of Alabama at Birmingham · USUniversity of Rhode Island · USBrown University · USIllinois College of Optometry · USMarshall B. Ketchum University · USOregon Health & Science University · USSUNY College of Optometry · USSwedish Medical Center · USUniversity of California, Los Angeles · USUniversity of Miami · US

Funding

Longitudinal validation of retinal biomarkers against cerebral imaging in preclinical Alzheimer's diseaseR01AG079241 · NIA · UNIVERSITY OF RHODE ISLAND · PI Jessica Alber · 2022 to 2026
$10.4M
A link between sleep-wake disturbances and enlarged perivascular spaces in youth with traumatic brain injuryK23HL150217 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI PIANTINO, JUAN ANDRES · 2020 to 2024
$826k
Characterizing Retinal Tissue Oxygenation, Structure, and Function in Alzheimer's DiseaseR21AG079794 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ARTHUR, EDMUND · 2023 to 2024
$408k
NHLBI NIH HHS K23 HL150217NHLBI NIH HHS K23HL150217-04NIA NIH HHS R01 AG079241NIA NIH HHS R01AG079241NIA NIH HHS R21 AG079794
6 · The paper itself

Abstract

backgroundCompared 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.

methods20 × 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.

resultsThe 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.

conclusionsOur 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.

Indexed as

Alzheimer DiseaseCapillariesAgedFluorescein AngiographyFundus OculiHumansMiddle AgedRetinal VesselsTomography, Optical CoherenceAlzheimer’s diseaseAPOE genotypingEarly risk detectionMid-peripheral capillary free zonesOptical coherence tomography angiographyPeriarteriole capillary free zonesPerivenule capillary free zones

Identifiers

PMID37828548
PMCPMC10568786
OpenAlexW4387571366

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.