Department of Neurosciences, University of California, San Diego, CA, USA.
Alzheimers Dement. 2010 Sep;6(5):412-9. doi: 10.1016/j.jalz.2009.12.003.
Apolipoprotein E varepsilon4 (APOE varepsilon4) allele carrier status has been well established as a risk factor for developing Alzheimer's disease. However, the specific influence of APOE varepsilon4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE varepsilon4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI).
A total of 516 aMCI participants aged 55-90 years who received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's MCI treatment trial were evaluated. During the 36-month study period, neurocognitive and functional measures were collected. These measures were assessed over time for change and association with APOE varepsilon4 status. Generalized Estimating Equations were performed to model each outcome measure over the study period.
APOE varepsilon4 status had a significant impact on cognitive and functional decline on multiple measures; those who were APOE varepsilon4 positive had significantly more rapid decline in performance on all cognitive and functional measures except Number Cancellation and Maze tracing (P < .05). The greatest decline was seen in global measures of cognition and function including the Clinical Diagnostic Rating scale, followed by the Mini-Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.
These findings demonstrate that APOE varepsilon4 genotype is predictive of increased general rates of decline with global measures of cognition and function most affected. With accelerated declines in common clinical trial primary efficacy measures, APOE varepsilon4 status needs to be accounted for in treatment trials of MCI.
载脂蛋白 E varepsilon4（APOE varepsilon4）等位基因状态已被充分确立为发展为阿尔茨海默病的风险因素。然而，APOE varepsilon4 等位基因状态对轻度认知障碍（MCI）认知和功能下降速度的具体影响知之甚少。我们研究了 APOE varepsilon4 等位基因状态对遗忘型轻度认知障碍（aMCI）患者认知和功能下降测量的前瞻性关联。
共有 516 名年龄在 55-90 岁之间的 aMCI 参与者参加了阿尔茨海默病合作研究的 MCI 治疗试验，他们接受了安慰剂或维生素 E 治疗。在 36 个月的研究期间，评估了神经认知和功能测量。评估了这些措施在一段时间内的变化，并与 APOE varepsilon4 状态相关联。使用广义估计方程（Generalized Estimating Equations）对研究期间的每个结果指标进行建模。
APOE varepsilon4 状态对多种认知和功能测量的下降有显著影响；APOE varepsilon4 阳性的人在所有认知和功能测量中，除了数字取消和迷宫追踪外，认知和功能下降速度明显更快（P<.05）。在全球认知和功能测量中，包括临床诊断评分量表、简易精神状态检查量表、全球恶化量表和阿尔茨海默病评估量表认知子量表，下降幅度最大。
这些发现表明，APOE varepsilon4 基因型与全球认知和功能的普遍下降速度相关，影响最大。由于常见临床试验主要疗效测量的加速下降，APOE varepsilon4 状态需要在 MCI 的治疗试验中得到考虑。
