Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain.
J Alzheimers Dis. 2012;31(3):517-26. doi: 10.3233/JAD-2012-120223.
In this study functional magnetic resonance imaging (fMRI) is used to investigate the functional brain activation pattern in the preclinical stage of AD (pre-AD) subjects during a visual encoding memory task. Thirty subjects, eleven in the pre-AD stage, with decreased cerebrospinal fluid levels of Aβ42 (<500 pg/ml), and 19 controls with normal Aβ42 levels (CTR) were included. fMRI was acquired during a visual encoding task. Data were analyzed through an Independent Component Analysis (ICA) and region-of-interest-based univariate analysis of task-related BOLD signal change. From the ICA decomposition, we identified the main task-related component, which included the activation of visual associative areas and prefrontal executive regions, and the deactivation of the default-mode network. The activation was positively correlated with task performance in the CTR group (p < 0.0054). Within this pattern, subjects in the pre-AD stage had significantly greater activation of the precuneus and posterior cingulate cortex during encoding. Subjects in the pre-AD stage present distinct functional neural activity before the appearance of clinical symptomatology. These findings may represent that subtle changes in functional brain activity precede clinical and cognitive symptoms in the AD continuum. Present findings provide evidence suggesting that fMRI may be a suitable biomarker of preclinical AD.
在这项研究中,我们使用功能磁共振成像(fMRI)来研究 AD 临床前期(pre-AD)患者在进行视觉编码记忆任务时大脑的功能激活模式。共纳入 30 名受试者,其中 11 名处于 pre-AD 阶段,脑脊液 Aβ42 水平降低(<500 pg/ml),19 名对照受试者 Aβ42 水平正常(CTR)。在进行视觉编码任务时采集 fMRI。通过独立成分分析(ICA)和基于感兴趣区域的任务相关 BOLD 信号变化的单变量分析来对数据进行分析。从 ICA 分解中,我们确定了主要的任务相关成分,该成分包括视觉联想区和前额叶执行区的激活以及默认模式网络的去激活。在 CTR 组中,激活与任务表现呈正相关(p < 0.0054)。在这种模式中,pre-AD 阶段的受试者在编码期间前扣带回和后扣带回皮质的激活显著增加。在出现临床症状之前,pre-AD 阶段的受试者表现出明显不同的功能神经活动。这些发现可能表明,在 AD 连续体中,大脑功能活动的细微变化先于临床和认知症状。目前的研究结果提供了证据表明,fMRI 可能是 pre-AD 的一种合适的生物标志物。