University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.
Neurobiol Aging. 2012 Apr;33(4):832.e15-22. doi: 10.1016/j.neurobiolaging.2011.07.016. Epub 2011 Sep 9.
The apolipoprotein E (APOE) gene may act differently in young and old persons, known as antagonistic pleiotropy. We therefore examined the prospective associations between the APOE ε4 allele and cognitive functioning, and the modifying effect of age, in 375 nondemented adults (mean age 57 ± 10 years; follow-up period 3.8 ± 0.2 years) with available data on APOE genotype and cognitive functioning, within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) cohort study. Neuropsychological tests assessing memory performance and executive functioning were performed at baseline and follow-up, and composite z-scores were calculated. Age significantly modified the association of APOE ε4 with change in memory performance (p interaction = 0.02). In persons ≤ 57 years (median split), an APOE ε4 allele was associated with an increase in immediate recall (B = 0.42; 95% confidence interval [CI], 0.17 to 0.66) and delayed recall (B = 0.37; 95% CI, 0.09 to 0.64), while in persons > 57 years, an APOE ε4 allele was associated with decline in immediate recall (B = -0.25; 95% CI, -0.52 to 0.01). Our findings suggest that the APOE ε4 allele has a differential effect on change in verbal memory performance depending on age, consistent with the hypothesis of antagonistic pleiotropy.
载脂蛋白 E (APOE) 基因在年轻人和老年人中的作用可能不同，这被称为拮抗多效性。因此，我们在 SMART-MR（动脉疾病第二次表现磁共振）队列研究中，检查了 APOE ε4 等位基因与认知功能之间的前瞻性关联，以及年龄的修饰作用，该研究纳入了 375 名无痴呆的成年人（平均年龄 57 ± 10 岁；随访期 3.8 ± 0.2 年），这些人具有 APOE 基因型和认知功能的可用数据。在基线和随访时进行了评估记忆表现和执行功能的神经心理学测试，并计算了综合 z 分数。年龄显著修饰了 APOE ε4 与记忆表现变化之间的关联（p 交互=0.02）。在≤57 岁的人群中（中位数分割），APOE ε4 等位基因与即刻回忆的增加相关（B=0.42；95%置信区间 [CI]，0.17 至 0.66）和延迟回忆（B=0.37；95%CI，0.09 至 0.64），而在>57 岁的人群中，APOE ε4 等位基因与即刻回忆的下降相关（B=-0.25；95%CI，-0.52 至 0.01）。我们的研究结果表明，APOE ε4 等位基因对言语记忆表现的变化有不同的影响，这与拮抗多效性的假设一致。
