Departments of Psychiatry and Neurology, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, Los Angeles, CA 90033, USA.
Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):260-7. doi: 10.1097/WAD.0b013e31819cb760.
The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) was modified for use in mild cognitive impairment (MCI) trials and tested in the ADCS MCI randomized clinical trial of donepezil, vitamin E, and placebo. We assessed feasibility for its use by determining whether or not: (1) it distinguished a medication effect at 6 months and 12 months, (2) baseline demographic or clinical characteristics predicted change, (3) there was an association between MCI-CGIC and change in other clinical measures in order to evaluate external or concurrent validity.
We used a generalized estimating equations approach for ordinal outcome data to test the effects of treatment, baseline characteristics, and change in clinical measures on the MCI-CGIC over 12 months, and ordinal logistic regression to assess the association between MCI-CGIC and change in clinical measures at 6 months and 12 months.
On the MCI-CGIC overall, 12.9% and 10.6% were rated as having improved, and 31.6% and 39.8% as having worsened over 6 months and 12 months, respectively. The MCI-CGIC did not distinguish the donepezil or vitamin E groups from placebo at 6 and 12 months treatment. Variables at screening or baseline that were associated with worse CGIC scores over 6 and 12 months included white race, greater years of education, worse depression, dementia severity rating, cognitive, and daily activities scores, and lower memory domain scores on a neuropsychological battery. Rate of worsening on the MCI-CGIC over 12 months was associated with change on the Alzheimer Disease Assessment Scale-cognitive and on executive function. Worsening at 6 months and 12 months, separately, were associated with the corresponding change in Alzheimer Disease Assessment Scale-cognitive, Activities of Daily Living, Beck Depression Inventory, Mini-Mental State Examination, Clinical Dementia Rating sum of boxes, memory, and executive function.
Change detected by the MCI-CGIC was associated with baseline clinical severity and with change in clinical ratings over 6 and 12 months, supporting the validity of a CGIC approach in MCI. The effect size of the donepezil-placebo difference was similar to that of other outcomes at 12 months. About 40% of MCI patients were judged worse and about 11% improved, consistent with clinical experience and other ratings.
为了在轻度认知障碍（MCI）试验中使用，并在 ADCS MCI 多奈哌齐、维生素 E 和安慰剂的随机临床试验中进行测试，对阿尔茨海默病合作研究-临床总体印象变化（ADCS-CGIC）进行了修改。我们通过确定以下几点来评估其使用的可行性：（1）它是否在 6 个月和 12 个月区分药物的效果，（2）基线人口统计学或临床特征是否预测变化，（3）MCI-CGIC 与其他临床测量指标的变化之间是否存在关联，以评估外部或同时有效性。
我们使用广义估计方程方法对有序结局数据进行分析，以检验治疗、基线特征和临床指标变化对 12 个月内 MCI-CGIC 的影响，并使用有序逻辑回归评估 MCI-CGIC 与 6 个月和 12 个月时临床指标变化之间的关联。
在总体 MCI-CGIC 上，分别有 12.9%和 10.6%的患者在 6 个月和 12 个月时被评为改善，31.6%和 39.8%的患者被评为恶化。在 6 个月和 12 个月时，MCI-CGIC 无法区分多奈哌齐或维生素 E 组与安慰剂组。在 6 个月和 12 个月的筛查或基线时，与 CGIC 评分更差相关的变量包括白种人、受教育年限更长、抑郁更严重、痴呆严重程度评分、认知和日常活动评分以及神经心理测验中记忆域评分较低。12 个月时 MCI-CGIC 恶化的速度与阿尔茨海默病评估量表-认知和执行功能的变化相关。6 个月和 12 个月时的恶化分别与阿尔茨海默病评估量表-认知、日常生活活动、贝克抑郁量表、简易精神状态检查、临床痴呆评定总和箱、记忆和执行功能的相应变化相关。
MCI-CGIC 检测到的变化与基线临床严重程度以及 6 个月和 12 个月时的临床评分变化相关，支持 CGIC 方法在 MCI 中的有效性。多奈哌齐-安慰剂差异的效应大小与 12 个月时的其他结果相似。约 40%的 MCI 患者被判断为更差，约 11%的患者有所改善，与临床经验和其他评估结果一致。
