School of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA.
Alzheimers Res Ther. 2023 Oct 12;15(1):172. doi: 10.1186/s13195-023-01312-8.
Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer's disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs. We hypothesized the mid-peripheral CFZs will be enlarged in CU older adults at high risk for AD compared to low-risk individuals.
20 × 20° optical coherence tomography angiography images consisting of 512 b-scans, 512 A-scans per b-scan, 12-µm spacing between b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea of 57 eyes of 37 CU low-risk (mean age: 66 years) and 50 eyes of 38 CU high-risk older adults (mean age: 64 years; p = 0.24) were involved in this study. High-risk participants were defined as having at least one APOE e4 allele and a positive first-degree family history of AD while low-risk participants had neither of the two criteria. All participants had Montreal Cognitive Assessment scores ≥ 26. The mid-peripheral CFZs were computed in MATLAB and compared between the two groups.
The periarteriole CFZ of the high-risk group (75.8 ± 9.19 µm) was significantly larger than that of the low-risk group (71.3 ± 7.07 µm), p = 0.005, Cohen's d = 0.55. The perivenule CFZ of the high-risk group (60.4 ± 8.55 µm) was also significantly larger than that of the low-risk group (57.3 ± 6.40 µm), p = 0.034, Cohen's d = 0.42. There were no significant differences in foveal avascular zone (FAZ) size, FAZ effective diameter, and vessel density between the two groups, all p > 0.05.
Our results show larger mid-peripheral CFZs in CU older adults at high risk for AD, with the potential for the periarteriole CFZ to serve as a novel retinal vascular biomarker for early AD risk detection.
与标准神经诊断技术相比，视网膜生物标志物为早期阿尔茨海默病（AD）风险筛查提供了一种可能的低成本、非侵入性替代方法。我们之前已经量化了认知正常（CU）的年轻和老年人群中的动脉周围和静脉周围毛细血管无血管区（周边中央 CFZ），作为视网膜组织氧合的新指标。AD 导致内视网膜血屏障破裂、周细胞丧失以及毛细血管无灌注或闭塞，从而可能导致周边中央 CFZ 扩大。我们假设与低风险个体相比，高 AD 风险的 CU 老年人群中周边中央 CFZ 会增大。
本研究共纳入了 37 名 CU 低风险（平均年龄：66 岁）和 38 名 CU 高风险（平均年龄：64 岁；p=0.24）老年个体的 57 只眼和 50 只眼的 20×20°光学相干断层扫描血管造影图像。这些图像由 512 个 b 扫描组成，每个 b 扫描有 512 个 A 扫描，b 扫描之间的间距为 12μm，每个 b 扫描位置的中央凹和配对的主要动静脉及其周围毛细血管都进行了 5 次平均处理。高风险参与者定义为至少有一个 APOE e4 等位基因，并且有 AD 一级亲属病史，而低风险参与者没有这两个标准。所有参与者的蒙特利尔认知评估分数均≥26。周边中央 CFZ 在 MATLAB 中计算，并在两组之间进行比较。
高风险组的动脉周围 CFZ（75.8±9.19μm）明显大于低风险组（71.3±7.07μm），p=0.005，Cohen's d=0.55。高风险组的静脉周围 CFZ（60.4±8.55μm）也明显大于低风险组（57.3±6.40μm），p=0.034，Cohen's d=0.42。两组间中央无血管区（FAZ）大小、FAZ 有效直径和血管密度无显著差异，均 p>0.05。
我们的结果表明，AD 高危 CU 老年人群中周边中央 CFZ 较大，动脉周围 CFZ 可能成为早期 AD 风险检测的新型视网膜血管生物标志物。
