Medical University of Vienna, Institute of Artificial Intelligence and Decision Support, Vienna, Austria; University of Oxford, Department of Engineering Science, Oxford, UK.
Medical University of Vienna, Institute of Artificial Intelligence and Decision Support, Vienna, Austria.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:31-38. doi: 10.1016/j.pnpbp.2018.12.013. Epub 2018 Dec 22.
So far, no cost-efficient, widely-used biomarkers have been established to facilitate the objectivization of Alzheimer's disease (AD) diagnosis and monitoring. Research suggests that event-related potentials (ERPs) reflect neurodegenerative processes in AD and might qualify as neurophysiological AD markers.
First, to examine which ERP component correlates the most with AD severity, as measured by the Mini-Mental State Examination (MMSE). Then, to analyze the temporal change of this component as AD progresses.
Sixty-three subjects (31 with possible, 32 with probable AD diagnosis) were recruited as part of the cohort study Prospective Dementia Registry Austria (PRODEM). For a maximum of 18 months patients revisited every 6 months for follow-up assessments. ERPs were elicited using an auditory oddball paradigm. P300 and N200 latency was determined with regard to target as well as difference wave ERPs, whereas P50 amplitude was measured from standard stimuli waveforms.
P300 latency exhibited the strongest association with AD severity (e.g., r = -0.512, p < 0.01 at Pz for target stimuli in probable AD subjects). Further, there were significant Pearson correlations for N200 latency (e.g., r = -0.407, p = 0.026 at Cz for difference waves in probable AD subjects). P50 amplitude, as measured by different detection methods and at various scalp sites, did not significantly correlate with disease severity - neither in probable AD, possible AD, nor in both subgroups of patients combined. ERP markers for the group of possible AD patients did not show any significant correlations with MMSE scores. Post-hoc pairwise comparisons between baseline and 18-months follow-up assessment revealed significant P300 latency differences (e.g., p < 0.001 at Cz for difference waves in probable AD subjects). However, there were no significant correlations between the change rates of P300 latency and MMSE score.
P300 and N200 latency significantly correlated with disease severity in probable AD, whereas P50 amplitude did not. P300 latency, which showed the highest correlation coefficients with MMSE, significantly increased over the course of the 18 months study period in probable AD patients. The magnitude of the observed prolongation is in line with other longitudinal AD studies and substantially higher than in normal ageing, as reported in previous trials (no healthy controls were included in our study).
目前，尚无经济有效的、广泛使用的生物标志物用于辅助阿尔茨海默病（AD）的客观诊断和监测。研究表明，事件相关电位（ERPs）反映了 AD 中的神经退行性过程，可作为神经生理学 AD 标志物。
首先，检验哪个 ERP 成分与 AD 严重程度的相关性最高，AD 严重程度由简易精神状态检查（MMSE）测量。然后，分析随着 AD 进展，该成分的时间变化。
63 名受试者（31 名可能 AD，32 名可能 AD）作为前瞻性痴呆登记奥地利（PRODEM）队列研究的一部分被招募。患者在最多 18 个月的时间内每 6 个月随访一次。采用听觉Oddball 范式诱发 ERPs。目标和差异波 ERPs 均测定 P300 和 N200 潜伏期，而标准刺激波形测定 P50 振幅。
P300 潜伏期与 AD 严重程度相关性最强（例如，Pz 区目标刺激时，可能 AD 患者 r= -0.512，p < 0.01）。此外，差异波 Cz 区时，N200 潜伏期有显著的 Pearson 相关（例如，可能 AD 患者 r= -0.407，p = 0.026）。通过不同的检测方法和不同的头皮部位测量的 P50 振幅，与疾病严重程度均无显著相关性 - 无论是在可能 AD 患者，还是在可能 AD 和确定 AD 患者的联合亚组中。可能 AD 患者的 ERP 标志物与 MMSE 评分无显著相关性。基线和 18 个月随访评估之间的事后两两比较显示，差异波 Cz 区时 P300 潜伏期有显著差异（例如，可能 AD 患者 p < 0.001）。然而，P300 潜伏期变化率与 MMSE 评分之间无显著相关性。
在可能 AD 中，P300 和 N200 潜伏期与疾病严重程度显著相关，而 P50 振幅则没有。与 MMSE 相关性最高的 P300 潜伏期在可能 AD 患者的 18 个月研究期间显著增加。观察到的延长幅度与其他纵向 AD 研究一致，且明显高于之前试验中的正常衰老程度（我们的研究中没有纳入健康对照）。
