Reduced Capillary Density in the Retina Indicative of the Progression of Neurodegeneration

Capillary networks are very dense, hundreds of capillaries passing through any given square millimeter of tissue. This network of microvessels is necessary to supply tissues with oxygen and nutrients. Unfortunately it declines in density with age, for reasons that are not well understood in detail. This likely contributes meaningfully to age-related loss of function, particularly in energy-hungry tissues such as muscles and the brain. Researchers here illustrate that loss of capillary density as observed in the retina - the eyes being a convenient window into that outpost of the central nervous system - correlates with the progression of neurodegeneration in the brain. Some thought should go towards finding the means to encourage greater maintenance and formation of capillary networks throughout the body.

The retina and brain share many neuronal and vasculature characteristics, and potential biomarkers may be present in the retina. Previous studies have analyzed digital fundus photographs and reported a range of retinal vessel alterations in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, images obtained from this technique can only provide information of retinal arterioles and venules measuring 60-300 μm in diameter. Optical coherence tomography angiography (OCTA) is a recent innovation that allows for further quantification of the retinal microvasculature and visualization of capillaries measuring 5-15 μm in diameter, which may be more representative of the entire microvascular network. Thus, the OCTA may be a potential non-invasive optical imaging tool to determine the presence and role of microvascular dysfunction in AD and cognitive impairment.

While there are a few OCTA studies investigating AD, there have been mixed conclusions. Some researchers reported finding significant reduction in the vessel density (VD) only in the superficial plexus, which complements histology findings and OCT studies since the superficial plexus mainly supplies the inner retinal layer. However, others reported finding changes only in the deep plexus. Studies have also used OCTA to examine participants with MCI, who are at higher risk for dementia and AD, but have drawn conflicting results as well.

To address these gaps, the purpose of the current study is to compare the retinal microvasculature metrics using OCTA, accounting for potential measurement bias and projection artifacts in participants with AD, MCI, and controls. We hypothesize that alterations in OCTA metrics as characterized by sparser vessel density and loss of vessel complexity will occur predominately within the superficial capillary plexus, in AD and to a lesser extent in MCI compared to controls.

24 AD participants, 37 MCI participants, and 29 controls were diagnosed according to internationally accepted criteria. OCTA images of the superficial and deep capillary plexus (SCP, DCP) of the retinal microvasculature were obtained using a commercial OCTA system. The main outcome measures were vessel density (VD) and fractal dimension (FD) in the SCP and DCP within a 2.5-mm ring around the fovea which were compared between groups.

Compared with controls, AD participants showed significantly sparser VD in both plexuses whereas MCI participants only showed reduction at the superficial plexus. In terms of FD, AD and MCI participants exhibited a loss of vessel complexity of the SCP when compared with controls. Our study adds further to the concept that there are possible progressive differences in retinal microvascular alterations between AD and MCI. Taken together with increasing evidence from other research, our current study demonstrates that differences in retinal microvascular changes using OCTA may potentially be used to identify and screen for AD and earlier cognitive phenotypes (i.e., MCI).



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