Olichney John M, Hillert Dieter G
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0662, USA.
Phys Med Rehabil Clin N Am. 2004 Feb;15(1):205-33. doi: 10.1016/s1047-9651(03)00103-7.
This article has reviewed several abnormalities in the cognitive ERPs of AD patients. These abnormalities are prominent from latencies of approximately 200 msec and later. In contrast, sensory-dependent evoked potentials, such as N100, are generally normal in AD. This finding is as one familiar with the neuropathology of AD would predict. Predilection sites in early AD include the medial temporal lobe, other limbic areas, and multimodal association cortices with sparing of primary sensory areas. Unimodal association cortex is involved in AD, but not as heavily as multimodal cortex. Particular advantages of studying a given ERP paradigm or component depend largely on the specific application or hypothesis being tested. A P300 paradigm can be useful in detecting a disorder of attention or in quantifying the effects of drugs that improve attention, such as the cholinesterase inhibitors. For the early diagnosis of AD or other memory disorders, a word-repetition paradigm with an explicit recognition task or one that fosters associative learning would be recommended. This article has discussed potential use of N400 in tracking disease progression. ERPs provide a flexible and powerful technique, with superb temporal resolution, which can be used as a probe into subtle "subclinical" abnormalities of cognitive processes. Despite being applied to AD for about 25 years since the early P300 studies, the full potential of ERPs in helping diagnose and treat AD patients has yet to be realized. In this era of rapidly evolving brain-imaging techniques, electrophysiologic data are important in advancing understanding of cognition. Brain-mapping techniques that can inform where and when key cognitive processes occur are finally emerging. A final example of potential clinical application of cognitive ERPs is in the development of rational combinational treatment of cognitive enhancing drugs. Along these lines, P300 investigations in epilepsy proved helpful in ranking the cognitive side effects of anticonvulsant drugs. Drug studies that use 2 x 2 combinational designs, which compare the effects of drug A, drug B, with A + B, are currently prohibitively expensive for full-scale clinical trials in AD. It is likely that precise ERP measures could hasten drug development in several ways. Smaller samples could be used, at lower cost, to test the cognitive effects of each specific drug combination. Optimal doses of combinational therapy perhaps could be identified by repeated within-subject ERP measures. Longitudinal changes in the ERP hold promise as a marker of individual responsivity to a particular agent, which could have diagnostic utility (eg, testing response to cholinergic or dopaminergic therapy). This horizon and many others remain wide open for well-planned explorations.
本文回顾了AD患者认知事件相关电位（ERP）的几种异常情况。这些异常在大约200毫秒及之后的潜伏期表现突出。相比之下，AD患者中依赖感觉的诱发电位，如N100，通常是正常的。这一发现正如熟悉AD神经病理学的人所预测的那样。AD早期的好发部位包括内侧颞叶、其他边缘区域以及多模式联合皮质，而初级感觉区域未受影响。单模式联合皮质在AD中也会受累，但程度不如多模式皮质。研究特定ERP范式或成分的特殊优势很大程度上取决于所测试的具体应用或假设。P300范式可用于检测注意力障碍或量化改善注意力的药物（如胆碱酯酶抑制剂）的效果。对于AD或其他记忆障碍的早期诊断，推荐采用具有明确识别任务或促进联想学习的单词重复范式。本文还讨论了N400在跟踪疾病进展方面的潜在用途。ERP提供了一种灵活且强大的技术，具有出色的时间分辨率，可用于探究认知过程中细微的“亚临床”异常。自早期P300研究以来，ERP应用于AD约25年了，但ERP在帮助诊断和治疗AD患者方面的全部潜力尚未实现。在这个脑成像技术快速发展的时代，电生理数据对于推进对认知的理解很重要。能够告知关键认知过程发生位置和时间的脑图谱技术终于出现了。认知ERP潜在临床应用的最后一个例子是在开发合理的认知增强药物联合治疗方面。沿着这些思路，对癫痫患者的P300研究证明有助于对抗惊厥药物的认知副作用进行排名。对于AD的大规模临床试验而言，采用2×2联合设计（比较药物A、药物B以及A + B的效果）的药物研究目前成本过高。精确的ERP测量很可能从几个方面加速药物研发。可以使用成本更低的较小样本，来测试每种特定药物组合的认知效果。联合治疗的最佳剂量或许可以通过对受试者重复进行ERP测量来确定。ERP的纵向变化有望作为个体对特定药物反应性的标志物，这可能具有诊断价值（例如，测试对胆碱能或多巴胺能治疗的反应）。对于精心规划的探索而言，这一前景以及许多其他方面仍有广阔的空间。
