载脂蛋白 E ε2ε4 基因型对非拉丁裔白种人阿尔茨海默病 (AD) 和轻度认知障碍 (MCI) 发展的影响。
The Effect of the APOE ε2ε4 Genotype on the Development of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in Non-Latino Whites.
机构信息
School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
出版信息
J Am Geriatr Soc. 2020 May;68(5):1044-1049. doi: 10.1111/jgs.16337. Epub 2020 Feb 4.
OBJECTIVES
To examine the associations of APOE ε2ε4 with the development of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in non-Latino whites.
DESIGN
Prospective longitudinal cohort study.
SETTING
Uniform Data Set from the National Alzheimer's Coordinating Center (NACC) between 2005 and August 2018 (data freeze in September 2018).
PARTICIPANTS
Participants who were non-Latino white, had an APOE genotype available, first visit with dementia free for AD cohort and both dementia and MCI free for MCI cohort, and had a minimum of one follow-up visit (n = 11 871 for AD cohort, and n = 8305 for MCI cohort).
MEASUREMENTS
The incidences of AD and MCI were determined based on consensus meetings at each Alzheimer's disease center. We used NACC-derived variables to define individuals experiencing incidents of AD and MCI at the initial visit as well as the follow-up visits.
RESULTS
Among participants in the AD cohort (N = 11 871), ε2ε4 accounted for 2.5%, ε2ε2 accounted for 0.4%, ε2ε3 accounted for 11.0%, ε4ε4 accounted for 4.4%, ε3ε4 accounted for 27.3%, and ε3ε3 accounted for 54.4%. Over an average of 4.6 years follow-up, 1857 (15.6%) developed AD dementia, with the range from 6.0% to 35.2% across the six groups. Compared to ε3ε3 carriers, ε2ε4 carriers exhibited an increased risk of incident AD (18.4% vs 11.7%; adjusted hazard ratio [aHR] = 1.74; 95% confidence interval [CI] = 1.32-2.30; P < .0001). Among participants in the MCI cohort (N = 8305), the average follow-up was 4.7 years, and 1912 (23.0%) developed MCI, with the range from 20.4% to 33.9% across the six groups. Compared to ε3ε3 carriers, ε2ε4 carriers exhibited an increased risk of incident MCI (27.5% vs 21.5%; aHR = 1.52; 95% CI = 1.15-1.99; P = .003).
CONCLUSIONS
The APOE ε2ε4 genotype is associated with the increased risk of AD and MCI in non-Latino whites. J Am Geriatr Soc 68:1044-1049, 2020.
目的
研究载脂蛋白 E（APOE）ε2ε4 与非拉丁裔白种人阿尔茨海默病（AD）和轻度认知障碍（MCI）发展的关系。
设计
前瞻性纵向队列研究。
地点
国家阿尔茨海默病协调中心（NACC）统一数据集，时间范围为 2005 年至 2018 年 8 月（数据冻结于 2018 年 9 月）。
参与者
非拉丁裔白种人，APOE 基因型可用，AD 队列首次就诊时无痴呆，MCI 队列时无痴呆和 MCI，且至少有一次随访（AD 队列 n = 11871，MCI 队列 n = 8305）。
测量
根据每个阿尔茨海默病中心的共识会议确定 AD 和 MCI 的发生率。我们使用 NACC 衍生变量来定义在初始就诊时以及随访时经历 AD 和 MCI 事件的个体。
结果
在 AD 队列（n = 11871）参与者中，ε2ε4 占 2.5%，ε2ε2 占 0.4%，ε2ε3 占 11.0%，ε4ε4 占 4.4%，ε3ε4 占 27.3%，ε3ε3 占 54.4%。在平均 4.6 年的随访中，有 1857 人（15.6%）发展为 AD 痴呆，6 组的范围为 6.0%至 35.2%。与 ε3ε3 携带者相比，ε2ε4 携带者发生 AD 的风险增加（18.4%比 11.7%；调整后的危险比[aHR] = 1.74；95%置信区间[CI] = 1.32-2.30；P < 0.0001）。在 MCI 队列（n = 8305）参与者中，平均随访时间为 4.7 年，有 1912 人（23.0%）发展为 MCI，6 组的范围为 20.4%至 33.9%。与 ε3ε3 携带者相比，ε2ε4 携带者发生 MCI 的风险增加（27.5%比 21.5%；aHR = 1.52；95%CI = 1.15-1.99；P = 0.003）。
结论
APOE ε2ε4 基因型与非拉丁裔白种人 AD 和 MCI 的风险增加相关。美国老年医学会杂志 68：1044-1049，2020。
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