Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain.
J Alzheimers Dis. 2013;36(1):165-75. doi: 10.3233/JAD-130062.
PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirteen healthy subjects were used as a control group (CTR). Subjects underwent a 10-min resting-state functional magnetic resonance imaging (fMRI) scan and also performed a visual encoding task. The analysis of resting-state fMRI data revealed alterations in the default mode network, with increased frontal connectivity and reduced posterior connectivity in AMC and decreased frontal and increased posterior connectivity in SMC. During task-related fMRI, SMC showed reduced activity in regions of the left occipital and left prefrontal cortices, while both AMC and SMC showed increased activity in a region within the precuneus/posterior cingulate, all as compared to CTR. Our findings suggest that fMRI can detect evolving changes in brain mechanisms in PSEN1 mutation carriers and support the use of this technique as a biomarker in Alzheimer's disease, even before the appearance of clinical symptoms.
PSEN1 突变是家族性阿尔茨海默病最常见的原因，几乎完全外显。在这里，我们研究了 19 名 PSEN1 突变携带者的脑功能改变：8 名有症状（SMC）和 11 名无症状（AMC）。无症状携带者的平均年龄比预计发病年龄小 12 岁。13 名健康受试者作为对照组（CTR）。受试者接受了 10 分钟的静息态功能磁共振成像（fMRI）扫描，并进行了视觉编码任务。静息态 fMRI 数据分析显示，默认模式网络发生改变，AMC 中额部连接增加，后部连接减少，SMC 中额部和后部连接减少。在任务相关 fMRI 中，SMC 显示左侧枕叶和左侧前额叶皮层区域的活动减少，而 AMC 和 SMC 都显示后扣带回/楔前叶内一个区域的活动增加，所有这些都与 CTR 相比。我们的研究结果表明，fMRI 可以检测 PSEN1 突变携带者脑机制的演变变化，并支持将这种技术作为阿尔茨海默病的生物标志物，即使在出现临床症状之前也是如此。
