University of Miami Miller School of Medicine (JAC, HJ, A-GYS, BB, TR, JW), Miami, Florida; Department of Ophthalmology (HJ, A-GYS, JW), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Neurology (HJ, BB, TR), University of Miami Miller School of Medicine, Miami, Florida; and The University of Miami Evelyn F. McKnight Brain Institute (HJ, TR, JW), Miami, Florida.
J Neuroophthalmol. 2024 Mar 1;44(1):30-34. doi: 10.1097/WNO.0000000000001954. Epub 2023 Jul 17.
Extensive evidence indicates that vasculopathy, especially the level of microcirculation, contributes to neurodegeneration in Alzheimer disease (AD). However, it is not easy to directly monitor cerebral microcirculation. The retinal microvasculature has been proposed as a surrogate measure to study cerebral vascular changes. Indeed, decreased retinal microvascular network densities were reported in patients with AD. We sought to determine the retinal capillary function (RCF, the efficiency of blood flow transferring in the capillary network) in patients with AD.
Twenty patients (age 60-84 years, mean ± SD: 72.8 ± 7.7 years) with AD and 14 age-matched cognitively normal controls (CN, age 62-81 years, mean ± SD: 68.6 ± 6.7 years.) were recruited. There were no differences in vascular risk factors, including smoking, hypertension, hyperlipidemia, Type 2 diabetes, and cardiovascular disease, between the groups. One eye of each subject in both groups was imaged. Retinal blood flow (RBF) was measured using a retinal function imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD.
RCF was 1.62 ± 0.56 nl/s/Dbox (mean ± SD) in the AD group, which was significantly lower than that (2.56 ± 0.25 nl/s/Dbox, P < 0.01) in the CN group. The change of RCF in the AD group represented 28% lower than in the CN group. RCF was significantly and positively correlated with RBF in the AD group (r = 0.98, P < 0.05) and in the CN group (r = 0.65, P < 0.05).
Our study is the first to demonstrate impaired retinal capillary function in patients with AD. The alteration of RCF was mainly due to decreased retinal blood flow, which is transferred by the capillary network. The RCF may be developed as a biomarker of impaired cerebral microcirculation in patients with AD.
大量证据表明血管病变，尤其是微循环水平，与阿尔茨海默病（AD）中的神经退行性变有关。然而，直接监测脑微循环并不容易。视网膜微血管系统已被提出作为研究脑血管变化的替代指标。事实上，AD 患者的视网膜微血管网络密度降低。我们试图确定 AD 患者的视网膜毛细血管功能（RCF，毛细血管网络中血流传递的效率）。
招募了 20 名（60-84 岁，平均±标准差：72.8±7.7 岁）AD 患者和 14 名年龄匹配的认知正常对照者（CN，62-81 岁，平均±标准差：68.6±6.7 岁）。两组之间在血管危险因素方面没有差异，包括吸烟、高血压、高血脂、2 型糖尿病和心血管疾病。两组中每个受试者的一只眼睛都进行了成像。使用视网膜功能成像仪测量视网膜血流（RBF），使用光学相干断层扫描血管造影术测量视网膜毛细血管密度（RCD，以分形维数 Dbox 表示）。RCF 定义为 RBF 与 RCD 的比值。
AD 组的 RCF 为 1.62±0.56 nl/s/Dbox（平均值±标准差），明显低于 CN 组（2.56±0.25 nl/s/Dbox，P<0.01）。AD 组 RCF 的变化比 CN 组低 28%。AD 组的 RCF 与 RBF 呈显著正相关（r=0.98，P<0.05），CN 组也呈显著正相关（r=0.65，P<0.05）。
我们的研究首次证明 AD 患者的视网膜毛细血管功能受损。RCF 的改变主要是由于视网膜血流减少，而视网膜血流是通过毛细血管网络传递的。RCF 可能作为 AD 患者脑微循环受损的生物标志物。
