Diamond E L, Miller S, Dickerson B C, Atri A, DePeau K, Fenstermacher E, Pihlajamäki M, Celone K, Salisbury S, Gregas M, Rentz D, Sperling R A
Department of Neurology, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115, USA.
Neurology. 2007 Sep 25;69(13):1331-41. doi: 10.1212/01.wnl.0000277292.37292.69.
Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated.
To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials.
Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images.
Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy.
The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. .
功能磁共振成像（fMRI）已显示出有望成为一种工具，用于表征阿尔茨海默病（AD）中大脑功能的改变，并用于概念验证性临床试验。与老年对照组相比，对AD患者的fMRI研究表明，在编码新刺激时海马和新皮质的激活发生了改变。然而，fMRI激活与标准化临床试验记忆测量指标的表现之间的关系尚未得到充分研究。
确定在联想记忆fMRI范式期间的激活模式是否与AD临床试验中使用的记忆测量指标的表现相关。
29名AD患者接受了神经心理学测试，包括AD评估量表（ADAS-Cog），以及联想编码fMRI范式。分数作为回归变量输入到SPM2分析中，以分析对新刺激与重复刺激（NvR）的fMRI差异激活。为了考虑脑萎缩，使用受试者的高分辨率结构图像进行了原生空间结构-功能分析。
ADAS-Cog言语记忆部分的表现以及ADAS-Cog总分与左侧颞上回（p = 0.0003；r = -0.51）和左侧前额叶（p = 0.00001；r = -0.63）皮质的NvR激活相关。在进行了更广泛神经心理学测试的亚组（n = 14）中，自由和提示选择性回忆测试的表现与这些相同区域的激活相关。即使考虑到萎缩，fMRI激活仍与表现相关。
功能磁共振成像（fMRI）激活与标准化记忆测量指标之间的关系支持在AD新型疗法的临床试验中，fMRI有潜力用于研究治疗反应的区域机制。
