Research has shown that due to similarities between retinal and cerebral vasculature, the retina and its vascular network can be used to help understand the characteristics of vascular cerebral pathologies. By analyzing the size, shape, and density of vascular blood flood within the retinal vascular network, conclusions could be drawn as to the risk for diseases like Alzheimer’s disease (AD).

Inés López Cuenca, PhD-candidate and research team conducted a study to determine the value of using optical coherence tomography angiography (OPTA) and other retinal vascular analysis tools to analyze changes in the retinal vascular structure as a predictor of AD risk. A novel and noninvasive technology, OPTA has the potential to serve as a beneficial prognostic tool.


Family History & Genotype

“With our study we wanted to determine whether in cognitively healthy subjects with two genetic risk factors for the development of Alzheimer’s disease (having a parent with AD and being a carrier of at least one ԑ 4 allele for the ApoE gene [apolipoprotein E]) vascular changes already appear at the retinal level,” López Cuenca explains. “It has been previously studied that subjects with established AD show vascular changes in the retina and brain, so it is interesting to know what happens in these subjects who do not yet have cognitive impairment. In addition, as cardiovascular risk factors such as hypercholesterolemia and hypertension are also risk factors for the development of AD, we wanted to know how the presence of these factors influenced patients at high risk of developing dementia.”

The study developed from part of the multicenter study The Cognitive and Neurophysiological Characteristics of Subjects at High Risk of Developing Dementia: A Multidimensional Approach (COGDEM) study. In 103 patients with a high genetic risk for developing AD—based on family history (FH) in which one or more parent had sporadic AD—or ApoE gene characterization identified—retinal vascular network was analyzed by OPTA and the imaging analysis software AngioTool and Erlangen-Angio-Tool (EA-Tool). Hypercholesterolemia and high blood pressure were also measured.

Participants were split into groups for vascular retinal network analysis based on FH of AD and ApoE ԑ4 characterization. These included FH+, FH-, ApoE ԑ4+, ApoE ԑ4-, combinations of both, as well as vascular risk factors.

Greater Presentation of Vascular Density

The results of the macular analysis using the EA-Tool showed a significantly higher macular vascular density in the FH+ ApoE ԑ4- group (25.22 [21.75-27.50]) compared with the FH+ ApoE ԑ4+ group (20.65 [18.26-25.63]) in the H12 sector of the C3 ring of the deep plexus (p-value = 0.041).

The results of the peripapillary analysis using the AngiaTool showed a statistically greater percentage area occupied by vessels in the FH+ ApoE ԑ4- group (47.52 [45.20-49.19]) compared with the FH+ ApoE ԑ4+ group (45.83 [44.29-47.22]); p-value = 0.031).

“Our findings show that in subjects who have two genetic risk factors for the development of AD and who are cognitively healthy, vascular changes already appear in the retina, and these changes may be the first vascular changes of the disease,” López Cuenca clarifies. “In addition, subjects with cardiovascular risk factors also show changes in retinal vascular density. These findings highlight the importance of retinal examination, and especially vascular analysis, in subjects at high genetic risk for the development of AD, as it could be used as an early biomarker of the disease.”

Based on the study findings, López Cuenca says that “doctors could include ophthalmological examinations in the diagnostic protocols for neurodegenerative diseases, as well as controlling arterial hypertension and hypercholesterolemia among the cardiovascular risk factors in subjects at high risk for the development of AD.”