Andrew Chapman

Introduction: Alzheimer’s disease (AD), is a neurodegenerative disease characterized pathologically by the progressive replacement of neurons with fibrillar amyloid β (Aβ) peptide in extracellular senile plaques and tau filaments in intracellular neurofibrillary tangles. Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Levels of plasma apoE vary between ApoE genotypes with APOE ε2/2 being the highest and ApoE ε4/4 being the lowest. ApoE4 is theorized to contribute to AD pathogenesis by modulating removal of soluble Aβ. One of the most promising potential biomarkers of AD progression are retinal microvascular changes. Deposition of Aβ plaques in arterioles and capillaries obfuscates molecular transfer leading to poor perfusion of tissue surrounding retinal vasculature. This causes further plaque accumulation in the vasculature resulting in early manifestations of AD. Optical coherence tomography angiography (OCTA) is a non-invasive diagnostic method with the ability to obtain high-resolution in vivo cross-sectional images of the eye. OCTA shows promise as a technique for detecting retinal microvascular changes in early cognitive deficit patients. Methods: Multiple groups are researching information tangentially related to this topic.  In one article, retinal vascular network abnormalities in amnestic mild cognitive impairment (aMCI) patients and healthy subjects were compared through OCTA. In another using OCTA, retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD were assessed and correlated with structural changes in each retinal neuronal layer. It also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Finally, comparing AD retinal changes from alternative pathology, and article compared 48 eyes of healthy control (HC) participants, 71 eyes of patients with Open Angle Glaucoma, and 49 eyes of AD patients from cadavers. Results:  It was found that aMCI patients showed a statistically significant reduced vascular density in superficial capillary plexus, deep capillary plexus and an increased Foveal Avascular Zone compared to controls. The second article, followed on this and found retinal microvasculature changes in patients with MCI owing to AD were detected using OCTA. It also showed lower vascular density of the Superficial Capillary Plexus was correlated with thinner Ganglion Cell Layer and Inner Plexiform Layer in these patients. This suggests that changes in the retinal microvasculature precede the reduction in the thickness of the retinal layers in patients with MCI owing to AD. Finally, in the discrimination of Patients with AD presented significantly greater losses of vascular density in the Deep Vascular Plexus and Outer Retinal Layer (ORL) thickness compared to Open Angle Glaucoma (p <0.001). Conclusion: In the early diagnosis of AD, OCTA can detect changes in retinal microvascular network in early cognitive deficits. The most sensitive alteration seems to be the enlargement of the FAZ. It was also determined that the ApoE genotype may also affect changes in retinal microvasculature and that analysis of ORL thickness and vessel density in DVP could potentially improve diagnostic capabilities and may provide a valuable approach for predicting of AD.

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