Foveal Avascular Zone and Choroidal Thickness Are Decreased in Subjects with Hard Drusen and without High Genetic Risk of Developing Alzheimer’s Disease

Abstract

A family history (FH+) of Alzheimer’s disease (AD) and ɛ4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ɛ4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ɛ4−, HD+) group compared with (i) both the (FH−, ɛ4−, HD−) and the (FH+, ɛ4+, HD+) groups in the superior and inferior points at 1500 μm, and (ii) the (FH+, ɛ4−, HD+) group in the superior point at 1500 μm. There were statistically significant differences in the superficial FAZ between the (FH+, ɛ4−, HD+) group and (i) the (FH+, ɛ4−, HD−) group and (ii) the (FH+, ɛ4+, HD−) group. In conclusion, ocular vascular changes are not yet evident in participants with a genetic risk of developing AD.

Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis

“…In addition, we found no statistically significant differences in the FAZ in the different study groups. These findings support those presented in a previous work, where no alterations in retinal vascular flow were found in subjects at high genetic risk of developing AD [ 21 ]. In patients with established AD, but in early stages of AD, no changes were found in the FAZ or in the percentage of oxyhemoglobin measured in the optic nerve head, demonstrating that the choroidal vascular plexus is affected early, even preclinically, in AD and the retinal plexus is affected in advanced stages of the disease [ 32 ].…”

“…Aβ oligomers found in drusen are toxic to human retinal pigment epithelium and cultured SH-SY5Y human neuroblastoma cells [ 29 ], and these findings are consistent with studies in patients with early AD, where large amounts of these highly toxic oligomers are found in the brain, causing neuronal dysfunction and synaptic disruption [ 36 ]. This could explain the possible alterations found in both the retina and choroid of subjects at high genetic risk of developing AD, who are also part of this study, and which we have reported in a previous work [ 21 , 30 ]. We have also demonstrated these alterations in the retina of a murine model of preclinical AD [ 37 ].…”

“…As described in previous works [ 21 , 30 ], this study is part of the project entitled “The cognitive and neurophysiological characteristics of subjects at high risk of developing dementia: a multidimensional approach” (COGDEM study).…”

“…The choroidal thickness was manually delimited from the outer hyperreflective line to the sclerochoroidal interface of the RPE; for the FAZ, it was also delimited manually. These procedures have been developed and explained in detail in previous works [ 21 , 32 ].…”

“…In addition, it has previously been shown that hyperlipidemia alone can cause structural changes in the choroidal and retinal vascular system, which may eventually lead to retinal dysfunction [ 20 ]. In fact, in previous work, we have shown that the presence of hard drusen (HD) in subjects without ApoE ɛ4 carriers and without a family history of AD causes a statistically significant reduction in choroidal thickness when compared with cognitively healthy subject carriers of ApoE ɛ4 with FH+ [ 21 ]. This reduction in choroidal thickness could mean a reduction in blood flow, which is also found in pathologies such as AMD, glaucoma, or diabetic retinopathy [ 22 , 23 , 24 ].…”