Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Laboratory for Cognitive and Experimental Neurophysiology, University Hospital Centre Zagreb, Zagreb, Croatia.
Curr Alzheimer Res. 2018;15(13):1244-1260. doi: 10.2174/1567205015666180911151116.
The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD.
The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid β peptide (β1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients.
The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia.
ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aβ1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients.
Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.
阿尔茨海默病（AD）的病理过程可能在其首次出现临床症状和 AD 症状之前 20-30 年开始，并且 AD 症状通常与其他原发性痴呆原因的症状重叠。因此，提高疾病的早期和鉴别诊断至关重要。脑电图通过事件相关电位（ERP）非侵入性测量已显示出在 AD 中的诊断潜力。
本研究的目的是比较 P300 和 N200 电位和反应时间（RT）与在脑脊液（CSF）中测量的常用蛋白质生物标志物的效率，包括淀粉样β肽（β1-42），总tau（t-tau），tau 蛋白在苏氨酸 181 处磷酸化（p-tau181），tau 蛋白在丝氨酸 199 处磷酸化（p-tau199），tau 蛋白在苏氨酸 231 处磷酸化（p-tau231）和视黄醇结合蛋白 1（VILIP-1）在轻度认知障碍（MCI）和 AD 患者中的 AD 鉴别诊断。
该研究涉及 49 名 AD 患者，28 名 MCI 患者，4 名健康对照者和 16 名其他原发性痴呆患者。
ERP（P300RT，N200RT，P300 计数和 N200 计数）与 CSF 蛋白质生物标志物呈中度至强相关。我们证实了先前观察到的 ERP 与神经心理学测试之间的中度至强相关性，并表明 AD 患者在接受乙酰胆碱酯酶抑制剂治疗时，P300 潜伏期和 RT 缩短。使用 ERP 和 RT，我们为 MCI 患者制定了用于确定 AD 可能性的预测模型，在我们的队列中检测到 56.3％的具有高 AD 发展风险的 MCI 患者。病理性 Aβ1-42 水平的 MCI 患者的 P300 潜伏期延长，表明 ERP 和 CSF 蛋白质生物标志物的组合可改善 MCI 患者的 AD 鉴别诊断。此外，结果表明 P300 潜伏期在区分 AD 和 FTD 患者方面具有潜力。
我们的数据为 AD 的鉴别诊断提供了可能的解决方案，并表明在临床实践中添加 ERP 可以提高 CSF 蛋白质生物标志物 t-tau，p-tau181，p-tau199，p-tau231 和 VILIP-1 的诊断效率。
