Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment

BackgroundAlzheimer’s disease (AD) is a major healthcare challenge, with existing diagnostics being costly/infeasible. This study explores retinal biomarkers from optical coherence tomography (OCT) and OCT angiography (OCTA) as a cost-effective and non-invasive solution to differentiate AD, mild cog...

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Main Authors: Yehia Ibrahim, Antonella Macerollo, Rodolfo Sardone, Yaochun Shen, Vito Romano, Yalin Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Aging Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2025.1477008/full
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author Yehia Ibrahim
Antonella Macerollo
Antonella Macerollo
Rodolfo Sardone
Rodolfo Sardone
Yaochun Shen
Vito Romano
Vito Romano
Yalin Zheng
Yalin Zheng
author_facet Yehia Ibrahim
Antonella Macerollo
Antonella Macerollo
Rodolfo Sardone
Rodolfo Sardone
Yaochun Shen
Vito Romano
Vito Romano
Yalin Zheng
Yalin Zheng
author_sort Yehia Ibrahim
collection DOAJ
description BackgroundAlzheimer’s disease (AD) is a major healthcare challenge, with existing diagnostics being costly/infeasible. This study explores retinal biomarkers from optical coherence tomography (OCT) and OCT angiography (OCTA) as a cost-effective and non-invasive solution to differentiate AD, mild cognitive impairment (MCI), and healthy controls (HCs).MethodsParticipants from the CALLIOPE Research Program were classified as “Dem” (AD and early AD), “MCI,” and “HCs” using neuropsychological tests and clinical diagnosis by a neurologist. OCT/OCTA examinations were conducted using the RTVue XR 100 Avanti SD-OCT system (VISIONIX), with retinal parameters extracted. Statistical analysis included normality and homogeneity of variance (HOV) tests to select ANOVA methods. Post-hoc analyses utilized Mann–Whitney U, Dunnett, or Tukey-HSD tests based on parameters’ normality and HOV. Correlations with age were assessed via Pearson or Spearman tests. A generalized linear model (GLM) using Tweedie regression modeled the relationship between OCT/OCTA parameters and MMSE scores, correcting for age. Another ordinal logistic GLM (OL-GLM) modeled OCT/OCTA parameters against classes, adjusting for multiple confounders.ResultsWe analyzed 357 participants: 44 Dem, 139 MCI, and 174 HCs. Significant microvascular density (VD) reductions around the fovea were linked with MCI and Dem compared to HCs. Age-related analysis associated thickness parameters with HCs’ old age. Our OL-GLM demonstrated significant thickness/volume reductions in Inner_Retina and Full_Retina layers. Foveal avascular zone (FAZ) area and perimeter were initially not correlated with cognitive decline; however, OL-GLM significantly associated FAZ perimeter enlargement with Dem and MCI groups. Significant average and inferior peripapillary RNFL thinning were linked to Dem and MCI groups.ConclusionThis is the first study to examine VD changes in G grid sections among Dem, MCI, and HCs. We found a significant association between various VD parameters and cognitive decline. Most macular thickness/volume changes did not correlate with cognitive decline initially; however, our OL-GLM succeeded, highlighting the importance of the confounders’ corrections. Our analysis excluded individual retinal layer parameters due to limitations; however, the literature suggests their value. Our study confirmed existing biomarkers’ efficacy and uncovered novel retinal parameters for cognitive decline, requiring further validation.
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publisher Frontiers Media S.A.
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series Frontiers in Aging Neuroscience
spelling doaj-art-3a33d9368c5e4b769347ff78e3357cd82025-08-20T02:45:53ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.14770081477008Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairmentYehia Ibrahim0Antonella Macerollo1Antonella Macerollo2Rodolfo Sardone3Rodolfo Sardone4Yaochun Shen5Vito Romano6Vito Romano7Yalin Zheng8Yalin Zheng9Department of Eye and Vision Sciences, University of Liverpool, Liverpool, United KingdomDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United KingdomDepartment of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United KingdomDepartment of Eye and Vision Sciences, University of Liverpool, Liverpool, United KingdomStatistics and Epidemiology Unit, Local Healthcare Authority of Taranto, Taranto, ItalyDepartment of Electrical Engineering and Electronics, University of Liverpool, Liverpool, United KingdomDepartment of Eye and Vision Sciences, University of Liverpool, Liverpool, United KingdomDepartment of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, ItalyDepartment of Eye and Vision Sciences, University of Liverpool, Liverpool, United KingdomLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United KingdomBackgroundAlzheimer’s disease (AD) is a major healthcare challenge, with existing diagnostics being costly/infeasible. This study explores retinal biomarkers from optical coherence tomography (OCT) and OCT angiography (OCTA) as a cost-effective and non-invasive solution to differentiate AD, mild cognitive impairment (MCI), and healthy controls (HCs).MethodsParticipants from the CALLIOPE Research Program were classified as “Dem” (AD and early AD), “MCI,” and “HCs” using neuropsychological tests and clinical diagnosis by a neurologist. OCT/OCTA examinations were conducted using the RTVue XR 100 Avanti SD-OCT system (VISIONIX), with retinal parameters extracted. Statistical analysis included normality and homogeneity of variance (HOV) tests to select ANOVA methods. Post-hoc analyses utilized Mann–Whitney U, Dunnett, or Tukey-HSD tests based on parameters’ normality and HOV. Correlations with age were assessed via Pearson or Spearman tests. A generalized linear model (GLM) using Tweedie regression modeled the relationship between OCT/OCTA parameters and MMSE scores, correcting for age. Another ordinal logistic GLM (OL-GLM) modeled OCT/OCTA parameters against classes, adjusting for multiple confounders.ResultsWe analyzed 357 participants: 44 Dem, 139 MCI, and 174 HCs. Significant microvascular density (VD) reductions around the fovea were linked with MCI and Dem compared to HCs. Age-related analysis associated thickness parameters with HCs’ old age. Our OL-GLM demonstrated significant thickness/volume reductions in Inner_Retina and Full_Retina layers. Foveal avascular zone (FAZ) area and perimeter were initially not correlated with cognitive decline; however, OL-GLM significantly associated FAZ perimeter enlargement with Dem and MCI groups. Significant average and inferior peripapillary RNFL thinning were linked to Dem and MCI groups.ConclusionThis is the first study to examine VD changes in G grid sections among Dem, MCI, and HCs. We found a significant association between various VD parameters and cognitive decline. Most macular thickness/volume changes did not correlate with cognitive decline initially; however, our OL-GLM succeeded, highlighting the importance of the confounders’ corrections. Our analysis excluded individual retinal layer parameters due to limitations; however, the literature suggests their value. Our study confirmed existing biomarkers’ efficacy and uncovered novel retinal parameters for cognitive decline, requiring further validation.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1477008/fullAlzheimer’s diseasedementiamild cognitive impairmentneurodegenerative disordersoptical coherence tomographyoptical coherence tomography angiography
spellingShingle Yehia Ibrahim
Antonella Macerollo
Antonella Macerollo
Rodolfo Sardone
Rodolfo Sardone
Yaochun Shen
Vito Romano
Vito Romano
Yalin Zheng
Yalin Zheng
Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
Frontiers in Aging Neuroscience
Alzheimer’s disease
dementia
mild cognitive impairment
neurodegenerative disorders
optical coherence tomography
optical coherence tomography angiography
title Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
title_full Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
title_fullStr Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
title_full_unstemmed Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
title_short Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
title_sort retinal microvascular density and inner thickness in alzheimer s disease and mild cognitive impairment
topic Alzheimer’s disease
dementia
mild cognitive impairment
neurodegenerative disorders
optical coherence tomography
optical coherence tomography angiography
url https://www.frontiersin.org/articles/10.3389/fnagi.2025.1477008/full
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