Longitudinal changes in retinal microvascular biomarkers as predictors of preclinical Alzheimer's disease

Abstract

Purpose : As the global prevalence of Alzheimer's diesase (AD) rises, interest in finding biomarkers which can detect this debilitating disease in the early stages has grown significantly. In recent years, the retina has emerged as a possible source of biomarkers with cross-sectional studies demonstrating microvascular changes in individuals with AD and mild cognitive impairment. The aim of this study is to ascertain if these microvascular changes occur over time in the preclinical stage of AD.

Methods : Optical Coherence Tomography Angiography was used to assess four microvascular biomarkers: vessel density (VD) at the macula Early Treatment of Diabetic Retionpathy Study (ETDRS) inner and outer ring area and around the optic nerve head, and the foveal avascular zone (FAZ) in cohort of 159 cognitively healthy twins (74 twin pairs and 11 singlteons) at baseline and during a two year follow-up period. Positron Emisson Tomography scans were acquired in 2015 and 2019 and used to determine the Amyloid Beta (Aβ) status of the participants (negative at both measurements; - - , converters from negative at baseline to positive at follow-up; -+, positive at both measurements; ++).

Results : Aβ -- status was found in 122 participants, Aβ -+ in 19 participants and Aβ ++ in 18 participants. A significant decrease in VD around the optic nerve head was noted over time among the Aβ++ participants (p=0.04), however VD between Aβ groups did not differ significantly. At both ETDRS macular ring regions, VD of the Aβ++ group was found to be significantly higher (p<0.01 for both inner and outer rings) compared to the other Aβ groups, with no significant change over time. There was no significant change in FAZ over time or between the three Aβ groups. Spaghetti plots in figure 3a and b illustrate these changes around the optic nerve head and macular inner ring.

Conclusions : The results of our study suggest that changes in retinal VD may begin in the preclinical phase, revealing distinct patterns at both the macula and optic nerve head. Further longitudinal studies with a longer follow-up design and known amyloid pathology are necessary to validate these observations.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Vessel density changes of the Aβ groups over time around the optic nerve head

 

Vessel density changes of the Aβ groups over time at the macula inner ring