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利用人工神经网络确定阿尔茨海默病转基因小鼠的认知障碍和治疗效果。

Use of artificial neural networks to determine cognitive impairment and therapeutic effectiveness in Alzheimer's transgenic mice.

作者信息

Leighty Ralph E, Runfeldt Melissa J, Berndt Donald J, Schleif William S, Cracchiolo Jennifer R, Potter Huntington, Arendash Gary W

机构信息

The Byrd Alzheimer's Institute and The Florida Alzheimer's Disease Research Center, Tampa, FL 33647, United States.

出版信息

J Neurosci Methods. 2008 Jan 30;167(2):358-66. doi: 10.1016/j.jneumeth.2007.08.008. Epub 2007 Aug 19.

Abstract

Behavioral testing of transgenic mouse models of Alzheimer's disease (AD) is the functional endpoint for determining the effectiveness of therapeutic interventions and elucidating AD pathogenesis. Utilizing these mouse models, there have been remarkably few attempts to analyze multiple behavioral measures/tasks with higher-level computation techniques, either to distinguish performance between transgenic groups or to reveal any "overall" cognitive benefit of a given therapeutic. The present study compared the classificatory accuracy of artificial neural networks (ANNs) versus more traditional discriminant function analysis (DFA) using multiple behavioral measures/tasks from two AD transgenic mouse investigations. These investigations were to determine if AD transgenic mice could be cognitively-protected by either long-term caffeine administration (CA) or by a cognitively-stimulating environment (SE). Both the entire set of behavioral measures and a subset of 8 cognitive-based measures were analyzed. Both classifiers revealed a beneficial "overall" effect of CA and SE to protect AD transgenic mice across multiple cognitive measures/tasks. However, for both CA and SE datasets, the ANN was superior to DFA for discerning transgenicity (non-transgenic vs. transgenic-controls) across multiple behavioral measures. These results indicate that ANNs have an excellent capacity to discriminate cognitive impairment in AD transgenic mice and thus designate ANNs as a novel, sensitive method for cognitive assessment in Alzheimer's research.

摘要

阿尔茨海默病(AD)转基因小鼠模型的行为测试是确定治疗干预有效性和阐明AD发病机制的功能终点。利用这些小鼠模型,很少有人尝试使用更高级的计算技术分析多种行为测量/任务,以区分转基因组之间的表现或揭示给定治疗的任何“整体”认知益处。本研究使用来自两项AD转基因小鼠研究的多种行为测量/任务,比较了人工神经网络(ANN)与更传统的判别函数分析(DFA)的分类准确性。这些研究旨在确定长期给予咖啡因(CA)或处于认知刺激环境(SE)是否可以对AD转基因小鼠提供认知保护。对整个行为测量集和基于认知的8项测量子集进行了分析。两个分类器均显示CA和SE对保护AD转基因小鼠免受多种认知测量/任务影响具有有益的“整体”效果。然而,对于CA和SE数据集,在多种行为测量中,ANN在辨别转基因性(非转基因与转基因对照)方面优于DFA。这些结果表明,ANN具有出色的能力来区分AD转基因小鼠的认知障碍,因此将ANN指定为阿尔茨海默病研究中一种新颖、灵敏的认知评估方法。

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