Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Neurology. 2010 Jun 15;74(24):1969-76. doi: 10.1212/WNL.0b013e3181e3966e. Epub 2010 May 12.
Previous cross-sectional fMRI studies in subjects with prodromal Alzheimer disease (AD) have reported variable results, ranging from hypoactivation, similar to patients with AD, to paradoxically increased activation or hyperactivation compared to cognitively normal older individuals. We have hypothesized that subjects in early phases of prodromal AD may experience a period of hippocampal hyperactivation, followed by loss of hippocampal activation as the disease progresses.
We studied 51 older individuals without dementia (Clinical Dementia Rating [CDR] at baseline of 0, n = 21, and 0.5, n = 30) with longitudinal clinical and neuropsychological assessments, as well as fMRI during a face-name associative memory paradigm. Whole brain and region-of-interest analyses were applied to the longitudinal fMRI data.
Subjects classified as CDR 0 at baseline showed no difference in fMRI activity over 2 years, whereas those who were CDR 0.5 at baseline demonstrated a decrease in fMRI activity in the right hippocampus (p < 0.001). Dividing the subjects on the basis of their clinical and neuropsychological change over the 2 years, we found that subjects with more rapid decline demonstrated both the highest hippocampal activation at baseline, and the greatest loss of hippocampal activation. These findings remained significant after accounting for age, hippocampal volume, and APOE epsilon4 carrier status.
Clinical decline is associated with loss of hippocampal activation in older subjects. Longitudinal fMRI provides a reliable indicator of brain activation over time, and may prove useful in identifying functional brain changes associated with cognitive decline on the trajectory toward clinical Alzheimer disease.
以前在有前驱期阿尔茨海默病（AD）的受试者中进行的横断面 fMRI 研究报告了不同的结果，范围从与 AD 患者相似的低激活到与认知正常的老年人相比反常地增加或过度激活。我们假设前驱期 AD 受试者可能经历一段时间的海马过度激活，然后随着疾病的进展，海马激活丧失。
我们研究了 51 名无痴呆的老年人（基线临床痴呆评定量表 [CDR] 为 0，n=21；和 0.5，n=30），进行了纵向临床和神经心理学评估，以及在面孔-名字联想记忆范式期间进行 fMRI。对纵向 fMRI 数据进行了全脑和感兴趣区分析。
基线时被分类为 CDR 0 的受试者在 2 年内 fMRI 活性无差异，而基线时为 CDR 0.5 的受试者则显示右侧海马 fMRI 活性下降（p<0.001）。根据 2 年内的临床和神经心理学变化对受试者进行分组，我们发现临床下降较快的受试者在基线时表现出最高的海马激活，以及最大的海马激活丧失。在考虑年龄、海马体积和 APOE ε4 携带者状态后，这些发现仍然具有统计学意义。
临床下降与老年人海马激活丧失有关。纵向 fMRI 提供了随时间变化的大脑激活的可靠指标，可能有助于识别与认知下降轨迹上向临床阿尔茨海默病相关的功能性脑变化。
