Cheng Ying-Chih, Huang Yu-Chen, Liu Hsing-Cheng
Department of Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan City, Taiwan.
Department of Public Health and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Dement Geriatr Cogn Disord. 2018;45(5-6):335-352. doi: 10.1159/000490175. Epub 2018 Jul 24.
The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer's disease (AD). However, its effect on an individual's response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status.
Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR).
Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: -0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups.
APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.
载脂蛋白Eε4（APOEε4）基因型是阿尔茨海默病（AD）的主要遗传风险因素。然而，其对个体治疗反应的影响尚不清楚。许多研究报告称，APOEε4的存在与否可能会影响乙酰胆碱酯酶抑制剂（AChEIs）的治疗反应，但结果并不一致。本研究进行了系统评价和荟萃分析，以评估AChEIs治疗反应与APOEε4携带者状态之间的关联。
纳入报告了APOEε4基因型的AD患者的临床研究进行分析。认知结局通过简易精神状态检查表（MMSE）、阿尔茨海默病评估量表认知分量表（ADAS-cog）或认知能力筛查工具（CASI）的变化来衡量。采用随机效应模型计算标准化均数差（SMD）和比值比（OR）。
在筛选的284篇摘要中，确定了38项研究，其中30项纳入荟萃分析。18项研究提供了评估APOEε4与AChEIs认知结局之间关联的连续数据。APOEε4携带者和非携带者的认知结局无显著差异（SMD = 0.022，95%CI：-0.089至0.133，p = 0.702，I² = 55.3%）。纳入了12项二元数据研究，两组之间也无显著差异（OR = 1.164，95%CI：0.928至1.459，p = 0.189，I² = 16.4%）。亚组分析表明，两组中AChEIs均比安慰剂显著更有效。
APOEε4携带者状态对AD患者AChEIs的治疗反应无显著影响。无论APOEε4携带者状态如何，与安慰剂相比，AChEIs均具有积极的治疗效果。
