3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer's disease
3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer's disease
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DOI：
10.1093/brain/awm112
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发表时间：
2007-07-01
期刊：
影响因子：
14.5
通讯作者：
Jack, Clifford R., Jr.
中科院分区：
文献类型：
--
作者：
Whitwell, Jennifer L.;Przybelski, Scott A.;Jack, Clifford R., Jr.
轻度认知障碍（MCI），特别是遗忘亚型（aMCI），被认为是正常衰老和临床上可能的阿尔茨海默病（AD）诊断之间的过渡阶段。aMCI构建体是特别有用的，因为它提供了评估在大多数受试者中代表前驱AD的临床阶段的机会。本研究的目的是评估从aMCI到进展为AD期间多个系列MRI的脑萎缩进展。选择符合aMCI临床标准的33例受试者，进行3次连续MRI扫描：第一次扫描与AD诊断前3年相似，第二次扫描与1年前相似，第三次扫描在AD诊断时进行。一组33名健康对照者与研究队列年龄和性别匹配。使用基于体素的形态测定法（VBM）评估aMCI受试者在每个时间点与对照组相比的灰质萎缩模式。使用定制模板和先验概率图来避免归一化和分割偏差。与对照组相比，在AD诊断前3年的aMCI受试者扫描中的灰质丢失模式主要集中在内侧颞叶，包括杏仁核、前海马和内嗅皮质，并额外累及梭状回。在AD诊断前1年，脑萎缩的范围和程度进一步发展。此时，颞叶的萎缩扩展到包括颞中回，并延伸到颞叶的更后部区域，包括整个海马体。顶叶也开始受到影响。当受试者进展到AD的临床诊断时，灰质萎缩的模式变得更加广泛，内侧颞叶和颞顶联合皮质的受累更加严重，额叶首次出现大量受累。这种进展模式与AD的Braak和Braak神经病理学分期方案非常吻合。这表明，最早的变化发生在前内侧颞叶和梭状回，这些变化发生在至少3年前进展到AD的诊断。这些结果还表明，灰质萎缩的3D模式可能有助于预测aMCI受试者首次诊断AD的时间。
Mild cognitive impairment (MCI), particularly the amnestic subtype (aMCI), is considered as a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer's disease (AD). The aMCI construct is particularly useful as it provides an opportunity to assess a clinical stage which in most subjects represents prodromal AD. The aim of this study was to assess the progression of cerebral atrophy over multiple serial MRI during the period from aMCI to progression to AD. Thirty-three subjects were selected that fulfilled clinical criteria for aMCI and had three serial MRI scans: the first scan similar to 3 years before the diagnosis of AD, the second scan similar to 1 year before, and the third scan at the time of the diagnosis of AD. A group of 33 healthy controls were age and gender-matched to the study cohort. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI subjects at each time-point compared to the control group. Customized templates and prior probability maps were used to avoid normalization and segmentation bias. The pattern of grey matter loss in the aMCI subject scans that were 3 years before the diagnosis of AD was focused primarily on the medial temporal lobes, including the amygdala, anterior hippocampus and entorhinal cortex, with some additional involvement of the fusiform gyrus, compared to controls. The extent and magnitude of the cerebral atrophy further progressed by the time the subjects were I year before the diagnosis of AD. At this point atrophy in the temporal lobes spread to include the middle temporal gyrus, and extended into more posterior regions of the temporal lobe to include the entire extent of the hippocampus. The parietal lobe also started to become involved. By the time the subjects had progressed to a clinical diagnosis of AD the pattern of grey matter atrophy had become still more widespread with more severe involvement of the medial temporal lobes and the temporoparietal association cortices and, for the first time, substantial involvement of the frontal lobes. This pattern of progression fits well with the Braak and Braak neurofibrillary pathological staging scheme in AD. It suggests that the earliest changes occur in the anterior medial temporal lobe and fusiform gyrus, and that these changes occur at least 3 years before progression to the diagnosis of AD. These results also suggest that 3D patterns of grey matter atrophy may help to predict the time to the first diagnosis of AD in subjects with aMCI.