Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study.

Oana M Dumitrascu,Ayesha Sherzai,Dale S Sherman,Patrick D Lyden,Yonggang Shi,Alan D Czeszynski,Julia Sheyn,Dean Sherzai,Kenneth O Johnson,Maziyar M Khansari,Susan Cheng,Yosef Koronyo,Ryan Rosenberry,Steven Verdooner,Sally Frautschy,Maya Koronyo-Hamaoui,Keith L Black,Tania Torbati

doi:10.3390/cells10112926

Abstract

Introduction: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. Methods: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. Results: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). Conclusion: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Highlights

Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration
All subjects older than 40 years of age presenting to our Neurology clinic with subjective cognitive decline and interest in undergoing retinal fluorescence imaging were included in this cohort
Linear regression analyses revealed that the venous branching angle correlated with the distal mid-periphery amyloid count (p = 0.03) and the arterial inflexion index correlated with the posterior pole amyloid count (p = 0.02)

Summary

Introduction

Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. Results: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory. Dysfunctional pericytes in the blood-brain barrier (BBB) are significant contributors to the pathogenesis of vascular cognitive impairment, including cerebral small vessel and cerebral large vessel disease, as well as AD [28,43]. Post-mortem retinal vessels derived from patients with mild cognitive impairment (MCI) and AD exhibited early and progressive pericyte loss as well as Aβ accumulation inside retinal pericytes, correlating with similar

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