Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.
Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.
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DOI：
10.1002/ana.22105
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发表时间：
2010-12
影响因子：
11.2
通讯作者：
Stern, Chantal E.
中科院分区：
文献类型：
--
作者：
Quiroz, Yakeel T.;Budson, Andrew E.;Celone, Kim;Ruiz, Adriana;Newmark, Rardall;Castrillon, Gabriel;Lopera, Francisco;Stern, Chantal E.
对携带导致家族性阿尔茨海默病（FAD）的完全外显基因改变的个体进行检查，为研究疾病症状前的早期阶段提供了一个独特的模型。在阿尔茨海默病中，情景记忆和联想记忆的缺陷与海马系统内的结构和功能变化有关。本研究使用功能性磁共振成像（fMRI）对一组携带FAD的E280A早老素 - 1（PS1）基因突变、健康、年轻且认知完好的症状前个体（平均年龄33.7岁）的海马功能进行了检查。这些PS1受试者将在大约45岁时开始出现该疾病的首发症状。我们的目的是在临床症状出现前数年检查海马功能。
20名携带与阿尔茨海默病相关的E280A PS1突变的个体和19名PS1阴性对照受试者参与了研究。两组在年龄、性别、教育水平和神经心理学测试表现方面相匹配。所有参与者在飞利浦1.5T fMRI扫描仪中执行一项面孔 - 名字联想编码任务。分析重点关注海马系统。
尽管行为表现相同，但与匹配的对照组相比，症状前PS1突变携带者在对新的面孔 - 名字联想进行编码时，右侧前海马的激活增加。
我们的研究结果表明，在FAD中，海马记忆系统的功能变化发生在认知能力下降之前数年。FAD中海马生理学的这些症状前变化表明，联想编码过程中的海马fMRI模式也可能为散发性阿尔茨海默病提供一种临床前生物标志物。
The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer’s disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Twenty carriers of the Alzheimer’s-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Philips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.
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影响因子：
5.7
作者：
Maldjian, JA;Laurienti, PJ;Burdette, JH
通讯作者：
Burdette, JH
影响因子：
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作者：
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作者：
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1.2
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Aguirre-Acevedo, D. C.;Gomez, R. D.;Lopera, F.
通讯作者：
Lopera, F.
影响因子：
10.6
作者：
Freire, L;Roche, A;Mangin, JF
通讯作者：
Mangin, JF