APOE modifies the association between Aβ load and cognition in cognitively normal older adults
APOE modifies the association between Aβ load and cognition in cognitively normal older adults
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DOI：
10.1212/wnl.0b013e31824365ab
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发表时间：
2012-01-01
期刊：
影响因子：
9.9
通讯作者：
Jack, C. R., Jr.
中科院分区：
文献类型：
--
作者：
Kantarci, K.;Lowe, V.;Jack, C. R., Jr.
目的：探讨[C-11]-匹兹堡化合物B (PiB) PET测定的β -淀粉样蛋白（A β）负荷与认知正常老年人认知功能的关系。方法：从2009年1月到2011年3月，我们研究了408名认知正常的老年人，他们参加了基于人群的梅奥诊所衰老研究（MCSA）。6个月内接受PiB PET和神经心理测试。PiB保留与认知功能之间的关系通过偏相关测量，并在调整年龄、性别和教育程度后使用线性回归测试与APOE状态的相互作用。结果：较高的PiB保留率与认知表现相关（Spearman偏r = -0.18; p < 0.01），特别是整个组参与者的记忆、语言、注意/执行和视觉空间处理领域。在控制APOE epsilon 4携带者和非携带者之间PiB值分布差异后，线性回归分析显示APOE状态改变了PiB保留与认知之间的关系（p = 0.02）。SPM分析显示，APOE epsilon 4携带者的认知表现与额叶、颞叶和顶叶关联皮层中的A β沉积有关（p < 0.001）。结论：在认知正常的老年人中，PiB保留与认知功能之间存在一定的关联，APOE状态改变了a β负荷与认知功能之间的关系。在APOE - epsilon 4携带者中，β负荷与更严重的认知障碍相关，而APOE - epsilon 4非携带者的认知功能受A - β负荷的影响较小，这表明APOE同工型调节了A - β对认知功能的有害影响。神经病学(R) 2012；78: 232 - 240
Objective: To determine the relationship between beta-amyloid (A beta) load as measured by [C-11]-Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults.Methods: We studied 408 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through March 2011. The participants underwent PiB PET and neuropsychometric testing within 6 months. The association between PiB retention and cognitive function was measured by partial correlation and an interaction with APOE status was tested using linear regression after adjusting for age, sex, and education.Results: Higher PiB retention was associated with cognitive performance (Spearman partial r = -0.18; p < 0.01), specifically the memory, language, attention/executive, and visual-spatial processing domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status on linear regression analysis even after controlling for the differences in the distribution of PiB values among APOE epsilon 4 carriers and noncarriers (p = 0.02). Cognitive performance was associated with the A beta deposition in the frontal, temporal, and parietal lobe association cortices in APOE epsilon 4 carriers on SPM analysis (p < 0.001).Conclusion: There is a modest association between PiB retention and cognitive function in cognitively normal older adults and this relationship between A beta load and cognitive function is modified by APOE status. Whereas A beta load is associated with greater cognitive impairment in APOE epsilon 4 carriers, the cognitive function in APOE epsilon 4 noncarriers is influenced less by the A beta load, suggesting that APOE isoforms modulate the harmful effects of A beta on cognitive function. Neurology (R) 2012; 78: 232-240