The role of APOE-ε4 in longitudinal cognitive decline -: MacArthur studies of successful aging
The role of APOE-ε4 in longitudinal cognitive decline -: MacArthur studies of successful aging
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DOI：
10.1212/01.wnl.0000055875.26908.24
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发表时间：
2003-04-08
期刊：
影响因子：
9.9
通讯作者：
Seeman, TE
中科院分区：
文献类型：
--
作者：
Bretsky, P;Guralnik, JM;Seeman, TE
背景资料：虽然是晚发性AD的遗传危险因素，但APOE基因的第4等位基因对认知功能的影响仍不清楚。目的：探讨载脂蛋白E基因（APOE）第4等位基因在纵向认知功能减退中的作用。研究方法：在麦克阿瑟成功老龄化研究中纵向评估了认知功能的多项指标，该研究是一项基于人群的队列研究，基线时无明显损害。受试者为1988年至1989年招募的来自北卡罗来纳州达勒姆、东波士顿、马萨诸塞州和康涅狄格州纽黑文的965名白人和非洲裔美国男性和女性，年龄70 - 79岁，他们完成了两次随访评价，一次在3年时，另一次在7年时。结果如下：在第一次随访时，命名和空间能力的适度但显著的下降与APOE-4基因型的一个元素有关。在第二次随访中，APOE-4基因型与八种认知结果中的六种认知下降之间的关联更加明显和显著。7年后，APOE-是4个等位基因携带者的总体认知评分下降的可能性是非携带者的两倍（比值比= 2.0; 95%CI：1.1，3.6）。结论：APOE-是一个4的元素，与高功能老年队列中的认知能力下降相关，在随访7年后效果最明显。因此，作为等位基因4的一个元件，它可能在正常衰老的广泛领域中作为认知障碍的危险因素发挥作用，或者可能在长期前驱AD轨迹的早期发挥可检测的作用。
Background: While a genetic risk factor for late-onset AD, the effects of the is an element of4 allele of the APOE gene on cognitive functioning more generally remain unclear. Objective: To assess the role of the is an element of4 allele of the APOE gene in longitudinal cognitive decline. Methods: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. Results: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-is an element of4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-is an element of4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-is an element of4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. Conclusions: APOE-is an element of4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the is an element of4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.