Ibrahim, Yehia 
ORCID: 0000-0002-7483-9461, Macerollo, Antonella ORCID: 0000-0003-4322-2706, Sardone, Rodolfo ORCID: 0000-0003-1383-1850, Shen, Yaochun ORCID: 0000-0002-8915-1993, Romano, Vito and Zheng, Yalin
(2025)
Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment.
Frontiers in Aging Neuroscience, 17.
1477008-.
ISSN 1663-4365, 1663-4365
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Text
fnagi-1-1477008.pdf - Open Access published version Download (2MB) | Preview |
Abstract
<jats:sec><jats:title>Background</jats:title><jats:p>Alzheimer’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).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Participants 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 <jats:italic>U</jats:italic>, 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This 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.</jats:p></jats:sec>
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Alzheimer’s disease, dementia, mild cognitive impairment, neurodegenerative disorders, optical coherence tomography, optical coherence tomography angiography, retinal biomarkers |
| Divisions: | Faculty of Health and Life Sciences Faculty of Science and Engineering Faculty of Science and Engineering > School of Electrical Engineering, Electronics and Computer Science Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 05 Mar 2025 11:58 |
| Last Modified: | 04 Apr 2025 15:04 |
| DOI: | 10.3389/fnagi.2025.1477008 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3190668 |
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