Scarmeas Nikolaos, Habeck Christian, Anderson Karen E, Hilton John, Devanand Davangere P, Pelton Gregory H, Tabert Matthias H, Flynn Joseph, Park Aileen, Ciappa Alejandra, Tycko Benjamin, Stern Yaakov
Departments of Neurology,College of Physicians and Surgeons of Columbia University Medical Center; 622 West 168th St., PH 19th floor; New York, NY 10032, USA.
Am J Geriatr Psychiatry. 2004 Nov-Dec;12(6):596-605. doi: 10.1176/appi.ajgp.12.6.596.
Few previous studies have investigated the association between APOE genotype and brain activation during performance of cognitive tasks in healthy middle-aged and elderly subjects, and the results have been mixed. The authors investigated APOE-mediated differential brain activation in a group of healthy elderly subjects.
Using H215O positron emission tomography (PET), they imaged 32 healthy subjects (26 non-epsilon4 carriers and 6 epsilon4 carriers) performing a serial shape-recognition memory task under two conditions: Simple Demand (SD), in which one shape was presented in each study trial, and Titrated Demand (TD), in which study list length was adjusted so that each subject recognized words at approximately 75% accuracy. Multiple-regression analyses were performed, with the "activation" difference (TD-SD PET counts) as the dependent variable and the APOE genotype (presence versus absence of the epsilon4 allele) as the independent variable.
Compared with non-carriers, epsilon4 carriers exhibited significantly decreased TD-SD activation differences in the left superior temporal, right superior frontal, left postcental, left precuneus, and posterior cingulate gyrus because epsilon4 carriers (versus non-carriers) showed increased activation during the SD and decreased activation during the TD condition.
Patterns of brain activation during a nonverbal memory task differed as a function of APOE genotype and, therefore, of genetic risk for Alzheimer disease (AD). Differences in activation were not a reflection of task difficulty, but indicate memory-related altered cognitive processing. Brain regions with decreased activation in the epsilon4 subjects may result from subclinical incipient AD pathology and/or APOE-related neurophysiologic heterogeneity.
以往很少有研究调查载脂蛋白E（APOE）基因分型与健康中老年受试者在执行认知任务时大脑激活之间的关联，结果也不一致。作者在一组健康老年受试者中研究了APOE介导的大脑激活差异。
他们使用H215O正电子发射断层扫描（PET）对32名健康受试者（26名非ε4携带者和6名ε4携带者）在两种条件下执行连续形状识别记忆任务进行成像：简单需求（SD），即每个研究试验中呈现一个形状；滴定需求（TD），即调整研究列表长度，使每个受试者以大约75%的准确率识别单词。进行多元回归分析，以“激活”差异（TD - SD PET计数）作为因变量，APOE基因分型（存在与不存在ε4等位基因）作为自变量。
与非携带者相比，ε4携带者在左侧颞上回、右侧额上回、左侧中央后回、左侧楔前叶和后扣带回中表现出显著降低的TD - SD激活差异，因为ε4携带者（与非携带者相比）在SD期间激活增加，而在TD条件下激活减少。
在非语言记忆任务期间的大脑激活模式因APOE基因分型而异，因此也因阿尔茨海默病（AD）的遗传风险而异。激活差异不是任务难度的反映，而是表明与记忆相关的认知加工改变。ε4受试者中激活减少的脑区可能是由于亚临床早期AD病理和/或APOE相关的神经生理异质性所致。
