Department of Ophthalmology, 'Marqués de Valdecilla' University Hospital, Institute for Research 'Marqués de Valdecilla' Santander, University of Cantabria, Santander, Spain.
Cognitive Impairment Unit, Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 'Marqués de Valdecilla' University Hospital, Institute for Research 'Marqués de Valdecilla' (IDIVAL), University of Cantabria, Santander, Spain.
Alzheimers Res Ther. 2022 Apr 21;14(1):57. doi: 10.1186/s13195-022-00998-6.
To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer's disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI).
We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (Aβ 1-42), and beta-amyloid 1-40 (Aβ 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch's membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student's t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1.
We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aβ 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant.
We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.
为了评估光学相干断层扫描 (OCT) 的多种参数是否可作为阿尔茨海默病 (AD) 高危认知正常个体的筛查工具，评估其与已建立的脑脊液 (CSF) 核心 AD 生物标志物和磁共振成像 (MRI) 的潜在关系。
我们研究了 99 名来自瓦尔迪塞利亚记忆与大脑老化研究的参与者。这是一个用于多模态生物标志物发现和验证的前瞻性队列，包括年龄在 55 岁以上且没有痴呆的参与者。参与者接受了全面的神经心理学测试，并进行了结构 3T 脑 MRI、腰椎穿刺以获取 CSF 生物标志物（磷酸化-181-Tau（pTau）、总 Tau（tTau）、β-淀粉样蛋白 1-42（Aβ 1-42）和β-淀粉样蛋白 1-40（Aβ 1-40））。所有参与者均接受了 OCT 检查以测量视网膜神经节细胞层（GCL）、视网膜神经纤维层（RFNL）、Bruch 膜开口最小边缘宽度（BMO-MRW）和脉络膜厚度（CT）。在第一阶段，我们进行了单变量分析，使用了 Student's t 检验。在第二阶段，我们进行了多元分析，仅包括在第一阶段在名义水平上区分阳性/阴性生物标志物的那些 OCT 参数。
我们发现 pTau 和 tTau 阳性个体的 OCT 测量值与这些标志物阴性个体之间存在显著差异，最明显的是前者的 GCL 和 RFNL 更薄。在第二阶段，我们的因变量是 CSF 标志物的定量值和海马体积。Aβ 1-42/40 比值与 OCT 测量值无显著相关性，而 pTau 与 tTau 与 GCL 的相关性具有统计学意义，尤其是在黄斑颞部。此外，多元分析显示海马体积与 GCL 和 RFNL 之间存在显著相关性。然而，在经过错误发现率校正后，只有与海马体积的相关性仍然具有统计学意义。
我们发现 Tau（pTau）与神经退行性变生物标志物（tTau 和海马体积）与 GCL 变性之间存在显著相关性，并且在较小程度上与 RFNL 损伤相关。OCT 分析是一种非侵入性和廉价的生物标志物，可以检测认知无症状个体的神经退行性变。
