Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep.
Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep.
复制标题
载脂蛋白Eε4等位基因与阿尔茨海默氏病和神经原纤维缠结密度的风险的修改。
DOI：
10.1001/jamaneurol.2013.4215
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发表时间：
2013-12
期刊：
影响因子：
29
通讯作者：
Bennett, David A.
中科院分区：
文献类型：
--
作者：
Lim, Andrew S. P.;Yu, Lei;Kowgier, Matthew;Schneider, Julie A.;Buchman, Aron S.;Bennett, David A.
载脂蛋白E(ApoE)ε4等位基因是阿尔茨海默病(AD)常见且公认的遗传危险因素。睡眠巩固也与AD风险有关，以前的工作表明，APOE基因和睡眠可能相互作用，影响认知功能。目的：确定良好的睡眠巩固是否能减轻APOE基因与AD发病风险和AD病理负担的关系。前瞻性纵向队列研究，随访时间长达6年。以社区为基础。我们在Rush Memory and Aging Project中研究了698名没有痴呆的社区老年人(平均年龄81.7岁，77%是女性)的志愿者样本，跟踪调查了长达6年的时间。我们使用了长达10天的活动记录来量化睡眠巩固程度，并确定了APOE基因。受试者在长达6年的随访期内接受了AD的年度评估。对2 0 1例死亡受试者进行尸检，用免疫组织化学方法检测Aβ和神经原纤维缠结(NFT)病理改变，并进行定量。在随后的一段时间里，98人患上了阿尔茨海默病。在一系列COX比例风险模型中，较好的睡眠巩固减弱了ε4等位基因对AD发病风险的影响(每增加一次睡眠巩固，HR为0.67，95%CI为0.46-0.97p=0.036)。在一系列线性混合效应模型中，更好的睡眠巩固也减弱了ε4等位基因对认知衰退年率的影响(交互作用估计+0.048 SE=0.012 p<；0.001)。在死亡个体中，较好的睡眠巩固减弱了ε4等位基因对NFT密度的影响(交互作用估计−0.42SE=0.17P=0.016)，这解释了睡眠巩固对APOE基因型与临近死亡的认知之间的关联的影响。良好的睡眠巩固可以减弱APOE基因对AD发病和NFT病理的影响。对睡眠巩固的评估可以确定APOE阳性的个体是发生AD的高危人群，应该研究加强睡眠巩固的干预措施，作为潜在的有用手段来降低APOEε4+个体的AD和NFT病理风险。
The Apolipoprotein E (APOE) ε4 allele is a common and well-established genetic risk factor for Alzheimer Disease (AD). Sleep consolidation is also associated with AD risk and previous work suggests that APOE genotype and sleep may interact to influence cognitive function. To determine whether better sleep consolidation attenuates the relation of the APOE genotype to the risk of incident AD and the burden of AD pathology. Prospective longitudinal cohort study with up to 6 years of follow-up. Community-based. We studied a volunteer sample of 698 community dwelling older adults without dementia (average age 81.7 years; 77% female) in the Rush Memory and Aging Project followed for up to 6 years. We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation, and ascertained APOE genotype. Subjects underwent annual evaluation for AD over a follow-up period of up to 6 years. Autopsies were performed on 201 deceased participants, and Aβ and neurofibrillary tangle (NFT) pathology were identified by immunohistochemistry and quantified. Over a follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (HR 0.67 95%CI 0.46–0.97 p=0.036 per allele per 1SD increase in sleep consolidation). In a series of linear mixed effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline (interaction estimate +0.048 SE=0.012 p<0.001). In deceased individuals, better sleep consolidation attenuated the effect of the ε4 allele on NFT density (interaction estimate −0.42 SE=0.17 p=0.016), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death. Better sleep consolidation attenuates the effect of APOE genotype on incident AD and NFT pathology. Assessment of sleep consolidation may identify APOE positive individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and NFT pathology in APOE ε4+ individuals.
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影响因子：
11
作者：
Bennett, DA;Schneider, JA;Arnold, SE
通讯作者：
Arnold, SE
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作者：
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