Salloway Stephen, Correia Stephen, Richardson Sharon
Department of Clinical Neurosciences Brown Medical School, Rhode Island, USA.
Int Psychogeriatr. 2008 Feb;20(1):40-6. doi: 10.1017/S1041610207005650. Epub 2007 Jun 28.
This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI).
The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group.
There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups.
The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.
本文回顾了首次发表的关于胆碱酯酶抑制剂治疗轻度认知障碍（MCI）的短期、安慰剂对照试验所吸取的关键经验教训。
该研究是一项为期24周的安慰剂对照试验，旨在评估盐酸多奈哌齐（多奈哌齐）治疗MCI患者认知障碍的疗效和安全性。主要结局指标是意向性分析-末次观察结转组中的纽约大学段落测试和阿尔茨海默病协作研究临床医师总体变化印象。
在ITT-LOCF组中，多奈哌齐治疗对主要结局指标（纽约大学段落测试和ADCS CGI-C）无益处，但在完全可评估组的纽约大学段落测试以及两组的某些次要结局指标上有阳性结果。
结果强调了需要使用对MCI患者的变化可靠且敏感的主要认知和功能指标。在本研究中，情景记忆、精神运动速度和复杂注意力的指标最为敏感。需要功能性评定量表来测量个体受试者功能缺陷关键领域的变化，这些领域通常涉及工具性日常生活活动的执行方面。通过采用灵活给药可提高耐受性，将试验时长从6个月延长至12个月并纳入在试验期间更可能病情恶化的受试者来丰富样本，可能会增强疗效。
