Changes in retinal microvasculature in preclinical Alzheimer’s disease

(Image credit: AdobeStock/Unic)

Dutch investigators reported that changes in the vessel density (VD) are observed early in preclinical Alzheimer’s Disease (AD), with distinct variations between the optic nerve head (ONH) and the macula,¹ according to first author Katie R. Curro, BSc, BA. She is from the Department of Ophthalmology and Quality of Care, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands.

Diagnosing AD depends on identification of biomarkers amyloid beta (Aβ) and/or hyperphosphorylated tau (Ptau).² However, according to Ms. Curro and colleagues, identifying them requires expensive or invasive procedures such as positron emission tomography (PET) and lumbar puncture, which are not readily available in every community and are usually only performed when an individual is referred to a memory clinic.

“Finding an inexpensive and patient-friendly biomarker for detection of AD could enable early detection, paving the way for initiation of treatment to prevent or slow disease progression before symptoms occur,” they explained.

They went on to explain that biomarkers such as VD in the superior capillary plexus (SCP), deep capillary plexus (DCP), and foveal avascular zone (FAZ) are promising because previous studies have reported changes in vascular density in the brain and retina in AD.^3,4 Cross-sectional studies have reported decreases in the SCP and DCP in patients with mild cognitive impairment and AD and enlargement or no change in the FAZ.^5-14 However, very few studies have looked at the preclinical AD stage and those that did reported inconsistent results.

To that end, the researchers investigated if changes in the VD and FAZ occur in the preclinical phase of AD over time.

They performed optical coherence tomography angiography (OCTA) to image the VD and FAZ at baseline and during a 2-year follow-up period. PET was performed to determine the Aβ status of participants.

The longitudinal cohort study included 148 participants (54% women; mean age, 68.3 years at baseline and 70.3 years at follow-up) who were followed for a mean of 2.24 years). The participants then were divided into 3 groups: controls negative for Aβ at both measurements (Aβ−, n=116); converters who transitioned from negative to positive for Aβ between baseline and follow-up (Aβ−+, n=18); and participants positive for Aβ at both visits (Aβ++, n=14).

“The VDs of both Aβ+ groups demonstrated non-significant increases over time in the macula and ONH. The Aβ− group was found to have significantly higher VDs in the ONH and macula. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ−+ and Aβ− groups. No significant change was found in the FAZ values over time,” the investigators reported.

This study showed that the VD of the SCP was stable over the 2-year period in participants who are Aβ++ for longer than 4 years in contrast to the healthy controls and converters. However, the VD was distinctly higher in the Aβ++ participants in the macular inner and outer rings.

“OCTA offers a simple, non-invasive way to image and record changes in the VD, reinforcing the notion that it could be a potential biomarker to detect AD before cognitive decline is present, although the exact onset of these changes remains unclear. Future studies investigating VD as a potential biomarker for preclinical AD should focus on longer periods of time for which the participants’ Aβ status is known, to more accurately track these changes in the preclinical phase. Improved software and algorithms now available will enable not only the SCP to be accurately explored but also other microvascular areas that could have the potential to reveal new microvascular retinal biomarkers for preclinical AD,” the authors concluded.

References

1. Curro KR, van Nispen RMA, den Braber A, et al. Longitudinal assessment of retinal microvasculature in preclinical Alzheimer's Disease. Invest Ophthalmol Vis Sci. 2024;65; doi: https://doi.org/10.1167/iovs.65.12.2

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