Enlargement of Retinal Periarteriole Capillary Free Zones in Cognitively Unimpaired Older Adults at High Risk for Alzheimer’s Disease

Abstract

Purpose : Retinal biomarkers provide a potential low cost and non-invasive alternative for early diagnosis of Alzheimer’s disease (AD). We have previously found larger periarteriole and perivenule capillary free zones (peripheral CFZs) in cognitively unimpaired (CU) older versus young adults. In AD, there is breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion leading to potential enlargement of the peripheral CFZs. We hypothesized the peripheral CFZs will be enlarged in CU older adults at high risk for AD versus low-risk individuals.

Methods : The Spectralis II instrument was used to acquire 20×20-degree Optical Coherence Tomography Angiography images of both the central fovea and paired major arterioles and venules with their surrounding capillaries inferior to the fovea. Participants included 15 CU low-risk (mean age: 67 years) and 32 CU high-risk for AD (mean age: 65 years; p=0.22). High-risk adults had a positive first-degree family history of AD and at least one APOE e4 allele, while low-risk adults had no positive first-degree family history of AD and no APOE e4 allele. All participants had Montreal Cognitive Assessment (MoCA) scores ≥ 26. The peripheral CFZs were computed in Matlab as the linear distance from the edge of an arteriole or venule to the middle of the nearest capillaries within the superficial vascular plexus, and compared between the two groups.

Results : The periarteriole CFZ of the high-risk group (78.3 ± 9.43 µm) was significantly larger than that of the low-risk group (70.3 ± 8.05 µm), p = 0.007 with a large effect size (Cohen's d = 0.88). The perivenule CFZ of the high-risk group (61.8 ± 8.33 µm) was not significantly larger than that of the low-risk group (57.7 ± 5.22 µm), p = 0.107 but there was a trend, Cohen's d = 0.52. Between the two groups, there were no significant differences in vessel diameter, vessel distance from the fovea, and vessel linear distance, all p>0.05.

Conclusions : Our initial analysis shows that the width of the periarteriole CFZ is larger in CU older adults at high risk for AD. The periarteriole CFZ has the potential to serve as a novel retinal vascular biomarker for assessment of early AD risk and disease monitoring.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Larger periarteriole (red arrows) and perivenule CFZ (blue arrows) in a high-risk CU adult (b) versus low-risk CU adult (a).