Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline
Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline
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DOI：
10.1136/jnnp.2007.124149
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发表时间：
2008-06-01
影响因子：
11
通讯作者：
Dickerson, B. C.
中科院分区：
文献类型：
--
作者：
Miller, S. L.;Fenstermacher, E.;Dickerson, B. C.
目的：利用功能性磁共振成像（fMRI）研究在记忆任务期间海马体的激活是否能够预测轻度认知障碍（MCI）患者的认知衰退。
方法：25名患有MCI的老年人在fMRI扫描期间执行视觉场景编码任务，并在扫描后至少进行4年的临床随访。对fMRI数据进行基于假设的分析。首先，在群体水平上分析fMRI数据，以确定该记忆任务所涉及的海马结构区域。提取每个受试者与记忆相关的海马体激活的参数估计值（信号变化百分比），并使用线性回归模型进行分析，以确定海马体激活是否能预测认知衰退的程度或速率，通过临床痴呆评定量表总和（CDR - SB）的变化来衡量。
结果：在扫描后的5.9（1.2）年随访期间，受试者在认知衰退的程度和速率方面差异很大（CDR - SB的变化范围从0到6，速率范围从0到1个CDR - SB单位/年）。海马体激活程度越高，预示着随后认知衰退的程度和速率越大（p < 0.05）。即使在控制了基线损伤程度（CDR - SB）、年龄、教育程度和海马体积，以及性别和载脂蛋白E状态后，这一发现仍然存在。此外，探索性全脑分析得出了一致的结果，表明海马结构是唯一激活能预测认知衰退的脑区。
结论：在MCI患者中，与记忆任务相关的海马体激活程度越高，预示着扫描后认知衰退的程度和速率越大。fMRI可能提供一种生理成像生物标志物，有助于识别认知衰退风险最高的MCI亚组，以便可能纳入疾病修饰临床试验。
Objective: To use functional MRI (fMRI) to investigate whether hippocampal activation during a memory task can predict cognitive decline in individuals with mild cognitive impairment (MCI).Methods: 25 older individuals with MCI performed a visual scene encoding task during fMRI scanning, and were followed clinically for at least 4 years after scanning. A hypothesis driven analysis of fMRI data was performed. First, fMRI data were analysed at the group level to identify the regions of the hippocampal formation that were engaged by this memory task. Parameter estimates of each subject's memory related hippocampal activation (% signal change) were extracted and were analysed with a linear regression model to determine whether hippocampal activation predicted the degree or rate of cognitive decline, as measured by change in Clinical Dementia Rating Sum-of-Boxes (CDR-SB).Results: Over 5.9 (1.2) years of follow-up after scanning, subjects varied widely in degree and rate of cognitive decline (change in CDR-SB ranged from 0 to 6, and the rate ranged from 0 to 1 CDR-SB unit/year). Greater hippocampal activation predicted greater degree and rate of subsequent cognitive decline (p < 0.05). This finding was present even after controlling for baseline degree of impairment (CDR-SB), age, education and hippocampal volume, as well as gender and apolipoprotein E status. In addition, an exploratory whole brain analysis produced convergent results, demonstrating that the hippocampal formation was the only brain region where activation predicted cognitive decline.Conclusions: In individuals with MCI, greater memory task related hippocampal activation is predictive of a greater degree and rate of cognitive decline subsequent to scanning. fMRI may provide a physiological imaging biomarker useful for identifying the subgroup of MCI individuals at highest risk of cognitive decline for potential inclusion in disease modifying clinical trials.