Zeng Qingze, Luo Xiao, Li Kaicheng, Wang Shuyue, Zhang Ruiting, Hong Hui, Huang Peiyu, Jiaerken Yeerfan, Xu Xiaojun, Xu Jingjing, Wang Chao, Zhou Jiong, Zhang Minming
Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Front Aging Neurosci. 2019 Dec 17;11:350. doi: 10.3389/fnagi.2019.00350. eCollection 2019.
: The National Institute on Aging-Alzheimer's Association (NIA-AA) has proposed a biological definition of Alzheimer's disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages. : We selected individuals with AD pathology (A+T+) and healthy controls (HC, A-T-) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ cohort into three groups: (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups. : The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the d-AD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected. : We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.
美国国立衰老研究所 - 阿尔茨海默病协会（NIA - AA）提出了阿尔茨海默病（AD）的生物学定义：淀粉样蛋白和tau生物标志物均异常（A + T +）的个体将被定义为AD。目前尚不清楚为何生物学上确诊为AD的受试者会出现不同的认知状态。静息态功能磁共振成像（rsfMRI）为揭示生物学定义的AD队列中的脑活动模式提供了契机。因此，我们旨在研究存在AD病理但处于不同认知阶段的受试者的不同脑活动模式。
我们基于脑脊液（CSF）生物标志物选择了具有AD病理（A + T +）的个体和健康对照（HC，A - T -）。根据认知阶段，我们将A + T +队列分为三组：（1）临床前AD；（2）前驱AD；（3）痴呆型AD（d - AD）。我们比较了四组之间通过低频振幅分数（fALFF）方法测量的自发脑活动。
协方差分析（ANCOVA）结果显示，后扣带回皮质/楔前叶（PCC/PCu）的fALFF存在显著差异。此外，与HC相比，我们发现临床前AD阶段右侧额下回（IFG）的fALFF值增加，而前驱AD患者双侧楔前叶、右侧额中回（MFG）、右侧中央前回和中央后回的fALFF降低。在d - AD组中，检测到了脑区活动增强（右侧梭状回、右侧海马旁回（PHG）/海马和颞下回）和活动减弱（双侧楔前叶、左侧后扣带回皮质、左侧楔叶和枕上回）。
我们在生物学定义为AD的受试者的不同认知阶段发现了不同的脑活动模式。我们的研究结果可能有助于理解AD病理生理过程中导致认知变化的机制。
