Optical Coherence Tomography Angiography in Preclinical Alzheimer’s Disease

Abstract

Purpose : As a protrusion from the brain, the retina might reflect (pathological) changes in the brain. Some studies have shown decrease in vessel density and foveal avascular zone (FAZ) enlargement on OCTA in individuals suffering from Alzheimer’s disease (AD). This study aims to see if these changes are already present in the preclinical stages of AD, using a population of monozygotic twins.

Methods : 124 cognitively healthy individuals (ages 60-93) underwent [¹⁸F]flutemetamol amyloid PET scanning and OCTA (Cirrus 5000 angioplex). PET scans were visually rated for cortical amyloid positivity and volume weighted global cortical non-displaceable binding potential (BP_ND) was calculated as a continuous measure for amyloid beta (Aβ). Vessel densities for the inner and outer ring in the macular area were obtained, as well as FAZ size. OCTA data were averaged over both eyes. Differences between Aβ+ and Aβ- individuals with regards to OCTA data, as well as the relation between BP_ND and OCTA data, were investigated using Generalized Estimating Equations (GEE), corrected for age, gender, scan quality and diagnosis of diabetes. Twin correlations were obtained for OCTA data using Pearson correlation coefficients.

Results : 13 of 124 participants (10.5%) had a positive visual rating score for cortical Aβ on PET. Aβ+ individuals had significantly higher vessel density in both the inner (Δ=0.81, p<0.001) and outer (Δ=0.50, p=0.012) ring of the macular area than Aβ- individuals. There was no significant difference in FAZ size between Aβ+ and Aβ- individuals (Δ=-0.02mm³, p=0.387). None of the OCTA measures were significantly associated with BP_ND. Twin correlations were moderate to high for all OCTA parameters (r=0.50 - 0.85, p<0.001).

Conclusions : Contrary to what was expected based on earlier studies, retinal vessel density seems to be increased in individuals suffering from preclinical AD, while FAZ size is unchanged. The increase in vessel density may be a compensatory mechanism as early manifestation of microvascular damage in the retina. Further studies should elucidate the nature of this change, as well as its diagnostic abilities for preclinical AD.
Moderate to high twin correlations suggest OCTA measures to be mainly determined by shared factors, likely of a genetic origin in this elderly population.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.