Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease

Abstract

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P = 0.01 and P = 0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments.

Figure 1

Retinal zones utilized for retinal vascular analysis. Zone A is defined as the region from 0 to 0.5 disc diameters away from the disc margin, zone B is defined as the region from 0.5 to 1.0 disc diameters away from the disc margin and zone C is defined as the region from 0.5 to 2.0 disc diameters away from the disc margin. Retinal photograph from a healthy individual.

Figure 2

Boxplot comparison of (a) Central retinal venular equivalent caliber (CRVE), (b) Fractal dimension of the venular network (FDv) and (c) Asymmetry factor of the venular network (AFv) across HC (n=123) and AD (n=25) groups. The HC group includes individuals with high plaque burden (HC+), low plaque burden (HC−) and unknown plaque burden. AFv is also compared across HC− (n=30) and HC+ (n=15) subgroups (d).