Primary risk factors of neurodegenerative disorders are advanced age and cardiovascular disease. With the increase in life expectancy, new methods of screening are needed [
23]. At the level of cerebral microvasculature, there is a growing evidence of age-related drop in capillary numbers and density observed in humans [
24] and in rodents [
25,
26]. Diagnostic methods for detecting and defining neurodegenerative syndrome routinely used by neurologists such as CSF assessment, PET, and MRI are either limited by their invasive nature or high costs [
27]. Alzheimer’s disease (AD) is considered the most common type of dementia. Common ophthalmologic signs and symptoms of AD are visual field changes and decreased visual acuity [
28]. Pathologically, it is characterized by deposition of plaques and tangles that consist of amyloid and tau protein, respectively. It is estimated that retinal microvascular changes such as microaneurysms, soft or hard exudates, retinal hemorrhages, macular edema, intraretinal microvascular abnormalities, venous beading, new vessels, vitreous hemorrhage, or disc swelling are associated with cognitive decline [
29]. Moreover, other retinal alterations such as changes in the thicknesses of macular RNFL are associated with early changes in Alzheimer-type dementia [
30]. Although other studies showed a decrease in ganglion cell layer (GCL) [
31], the changes in RNFL and inner plexiform layer [
32] are associated with the neocortical Aβ accumulation, while GCL is not [
33]. A recent study evaluated OCTA findings in AD. The authors described enlarged FAZ measured by the OCTA device and decreased retinal vascular density and choroidal thickness which correlated with a decrease on Mini Mental State Examination. They attribute these changes to decreased angiogenesis caused by binding of vascular endothelial growth factor (VEGF) to Aβ plaques [
34•]. In a comparative study on twins, it was observed that a twin with AD had larger FAZ in SCP and thinner choroid compared with the healthy sibling [
35]. Similarly, in a study by Jiang et al., AD patients had reduced density of both SCP and DCP in comparison with controls, whereas patients with mild cognitive impairment had reduced density only in DCP and in the superior nasal quadrant [
36]. Thus, as the blood from the central retinal artery supplies firstly SCP and then DCP, reduced SCP density can lead to decreased blood flow through the outer layers of retina which may lead to continual loss of ganglion cell axons [
37].
In migraine, mainly peripapillary RNFL thickness is reduced, especially in patients with aura [
38]. One study demonstrated reduced parafoveal SCP density and superior RPC density in patients with migraine with aura compared with migraine without aura and healthy controls. Furthermore, patients with aura had enlarged FAZ. However, the authors speculate that this is probably associated with increased risk of retinovascular occlusion, normal tension glaucoma, and ischemic optic neuropathy among patients with migraine. The authors did not observe significant changes between migraine without aura and healthy controls [
39•].
The article by Nelis et al. describes changes in OCTA observed in 21 eyes of 11 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The patients showed decreased vessel density in DCP which the authors associate with Notch3 mutation in pericytes. However, only 9 patients included had confirmed Notch3 mutations [
15]. Notably, this corresponds to a report of OCT findings by Fang et al. where the inner arterial diameter and arterial to venous ratio of the inner and outer diameters correspond negatively to a number of small infarcts in the 7T MRI [
40].