Retinal Scans to Visualize the Loss of Capillary Density in the Central Nervous System

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The angiogenesis hypothesis of aging suggests that loss of capillaries throughout the body is an important driver of age-related decline. This loss must be a downstream consequence of other forms of damage and dysfunction, issues that lead to a disruption of the balance of signals and cell capabilities needed to maintain the network of capillary blood vessels. Hundred of capillaries pass through every square millimeter of tissue, allowing the bloodstream to nourish the resident cells. If the density of that network declines, then ever lesser amounts of oxygen and nutrients are delivered to the cells that need them. This is particularly important in tissues requiring a great deal of energy, such as muscles and the brain. As for all aspects of aging, of course, there is good evidence for this process of capillary loss to be relevant, but the relative size of the effect is unknown, when comparing against other processes of aging. Only when specific aspects of age-related decline can be repaired in isolation is it possible to see the size of their contribution.

The retina is considered a part of the central nervous system, and thus the eyes can act as a window into the state of aging in the brain and major nerves. In today’s open access paper, researchers report on the use of scanning technologies to visualize the decline in capillary density in the retina. This is a mark of aging, related to just how much deterioration and damage has taken place in tissues. This is why it correlates well to incidence of Alzheimer’s disease, I would expect. Alzheimer’s disease has many causes and disease processes, of which at least some, such as chronic inflammation in the central nervous system, can be credibly argued to disrupt the regenerative processes responsible for maintaining tissues and blood vessel networks.

Eyes reveal early Alzheimer’s disease

It’s known that patients with Alzheimer’s have decreased retinal blood flow and vessel density but it had not been known if these changes are also present in individuals with early Alzheimer’s or forgetful mild cognitive impairment who have a higher risk for progressing to dementia. Multicenter trials could be implemented using this simple technology in Alzheimer’s clinics. Larger datasets will be important to validate the marker as well as find the best algorithm and combination of tests that will detect high-risk subjects. The back of the eye is optically accessible to a new type of technology (OCT angiography) that can quantify capillary changes in great detail and with unparalleled resolution, making the eye an ideal mirror for what is going on in the brain.

Researchers recruited 32 participants who had cognitive testing consistent with the forgetful type of cognitive impairment, and age-, gender- and race- matched them to subjects who tested as cognitively normal for their age. All individuals underwent the eye imaging with OCT angiography. The data were analyzed to identify whether the vascular capillaries in the back of the eye were different between the two groups of individuals. Now the team hopes to correlate these findings with other more standard (but also more invasive) types of Alzheimer’s biomarkers as well as explore the longitudinal changes in the eye parameters in these subjects.

Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer’s Disease on optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) is a non-invasive clinical tool that can capture the retinal capillary microcirculation at the micrometer resolution. Previous retinal vascular studies using retinal functional imager and laser flowmetry have shown decreased flow in the temporal retinal vein and major parafoveal arterioles and venules in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) individuals. However, OCTA provides a unique opportunity to investigate the microvasculature in a specific retinal vascular plexus of interest. OCTA has demonstrated that retinal neural sub-layers are supplied by distinct capillary plexuses, each reflecting the metabolic demand of a particular neuronal layer. Importantly, we know that the inner retina layer in both the macula and optic disc bears the brunt of AD pathology including the loss of ganglion cells, thinning of the retinal nerve fiber layer (RNFL), and deposition of amyloid-β plaques according to histological and OCT structural imaging studies.

Our study shows that compared to matched cognitively normal controls, participants with early cognitive impairment demonstrated significantly decreased superficial parafoveal vessel density and blood flow. In addition, we found that parafoveal and peripapillary densities were positively correlated with the Montreal Cognitive Assessment (MoCA), a measure of overall cognitive impairment. Most importantly, we demonstrated the role of OCTA in detecting early capillary changes, which may represent potentially early, non-invasive biomarkers of AD. Future directions include a larger cohort as well as longitudinal studies that examine the temporal relationship between vascular damage and pathological loss of ganglion cells, their nerve fibers, and cognitive decline.

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