Predictive Power of Cognitive Biomarkers in Neurodegenerative Disease Drug Development: Utility of the P300 Event-Related Potential.

IF 3 4区 医学 Q2 NEUROSCIENCES
John Olichney, Jiangyi Xia, Kevin J Church, Hans J Moebius
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引用次数: 4

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD), and their associated deterioration of cognitive function are common causes of disability. The slowly developing pathology of neurodegenerative diseases necessitates early diagnosis and monitored long-term treatment. Lack of effective therapies coupled with an improved rate of early diagnosis in our aging population have created an urgent need for the development of novel drugs, as well as the need for reliable biomarkers for treatment response. These issues are especially relevant for AD, in which the rate of clinical trial drug failures has been very high. Frequently used biomarker evaluation procedures, such as positron emission tomography or cerebrospinal fluid measurements of phospho-tau and amyloid beta, are invasive and costly, and not universally available or accessible. This review considers the functionality of the event-related potential (ERP) P300 methodology as a surrogate biomarker for predicting the procognitive potential of drugs in clinical development for neurocognitive disorders. Through the application of standardized electroencephalography (EEG) described here, ERP P300 can be reliably measured. The P300 waveform objectively measures large-scale neuronal network functioning and working memory processes. Increased ERP P300 latency has been reported throughout the literature in disorders of cognition, supporting the potential utility of ERP P300 as a biomarker in many neurological and neuropsychiatric disorders, including AD. Specifically, evidence presented here supports ERP P300 latency as a quantitative, unbiased measure for detecting changes in cognition in patients with AD dementia through the progression from mild to moderate cognitive impairment and after drug treatment.

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认知生物标志物在神经退行性疾病药物开发中的预测能力:P300事件相关电位的应用
神经退行性疾病,如阿尔茨海默病(AD)及其相关的认知功能恶化是导致残疾的常见原因。神经退行性疾病的病理发展缓慢,需要早期诊断和监测长期治疗。由于缺乏有效的治疗方法,再加上老龄化人口早期诊出率的提高,迫切需要开发新型药物,以及可靠的生物标志物来衡量治疗反应。这些问题与阿尔茨海默病尤其相关,因为阿尔茨海默病的临床试验药物失败率非常高。常用的生物标志物评估程序,如正电子发射断层扫描或脑脊液测量磷酸化-tau和淀粉样蛋白,是侵入性的和昂贵的,并且不是普遍可用或可获得的。本综述考虑了事件相关电位(ERP) P300方法的功能,作为预测神经认知障碍临床开发药物的前认知潜力的替代生物标志物。通过标准化脑电图(EEG)的应用,可以可靠地测量ERP P300。P300波形客观地测量了大规模神经网络的功能和工作记忆过程。认知障碍的文献中都有ERP P300潜伏期增加的报道,这支持了ERP P300作为包括AD在内的许多神经和神经精神疾病的生物标志物的潜在用途。具体来说,本文提供的证据支持ERP P300潜伏期作为一种定量的、无偏倚的测量方法,用于检测AD痴呆患者从轻度到中度认知障碍的进展以及药物治疗后的认知变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neural Plasticity
Neural Plasticity NEUROSCIENCES-
CiteScore
6.80
自引率
0.00%
发文量
77
审稿时长
16 weeks
期刊介绍: Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.
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