Eagger S A, Harvey R J
Academic Department of Old Age Psychiatry, St. Mary's Hospital Medical School, St. Charles Hospital, London, England.
Alzheimer Dis Assoc Disord. 1995;9 Suppl 2:37-42.
Clinical Alzheimer disease (AD) is a heterogeneous disorder, and it is possible to subgroup patients by a number of different criteria. One such subgrouping is those who have a positive response to cholinergic therapy and those who do not. This phenomenon has been clearly recognised in a number of therapeutic trials of cholinesterase inhibitors and is likely to be an issue in clinical practice. Tacrine, the first cholinesterase inhibitor to be approved for the treatment of AD, has, at best, modest effects on 20-50% of patients and is associated with a high frequency of side effects, including liver transaminitis. The potential of clinical tests or other investigations to identify those patients who are more likely to respond to cholinergic therapy would be a valuable aid in the clinical use of these therapies. In this article we review the issue of heterogeneity in patient populations, in the design of trials and in the pharmacological compounds used in trials. We then summarise the findings of a number of small studies of potential response predictors, which include the use of psychometric tests, orthostatic blood pressure, pupillary dilation, the electroencephalogram, cerebrospinal fluid neurochemistry, and techniques involving functional imaging. Although some results are promising, generalisability is limited by the small numbers of patients studied and the frequent open nature of the designs used. The main conclusion that can be drawn is that adequate doses are required to achieve therapeutic plasma levels before nonresponse is accepted.
临床阿尔茨海默病（AD）是一种异质性疾病，可以根据多种不同标准对患者进行亚组划分。其中一种亚组划分是对胆碱能治疗有阳性反应的患者和无阳性反应的患者。这种现象在胆碱酯酶抑制剂的多项治疗试验中已得到明确认识，并且在临床实践中可能也是一个问题。他克林是首个被批准用于治疗AD的胆碱酯酶抑制剂，对20%至50%的患者充其量只有适度疗效，且伴有包括肝转氨酶升高在内的高频率副作用。通过临床试验或其他检查来识别那些更可能对胆碱能治疗产生反应的患者，将对这些疗法的临床应用有宝贵帮助。在本文中，我们回顾了患者群体、试验设计以及试验中使用的药理化合物方面的异质性问题。然后我们总结了一些关于潜在反应预测指标的小型研究结果，这些指标包括心理测量测试、直立性血压、瞳孔散大、脑电图、脑脊液神经化学以及涉及功能成像的技术。尽管一些结果很有前景，但由于研究的患者数量少以及所采用设计常见的开放性，可推广性受到限制。可以得出的主要结论是，在接受无反应之前，需要足够的剂量来达到治疗性血浆水平。
