探讨阿尔茨海默病行为变异型的临床解剖分离现象。
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease.
机构信息
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
出版信息
Alzheimers Res Ther. 2020 Nov 14;12(1):148. doi: 10.1186/s13195-020-00717-z.
BACKGROUND
We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers.
METHODS
We retrospectively included 150 participants, including 29 bvAD, 28 "typical" amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy.
RESULTS
bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85-0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71-0.84, all p < 0.05).
CONCLUSIONS
Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.
背景
我们之前发现，在行为变异型阿尔茨海默病（bvAD）中存在颞顶叶优势萎缩模式，额叶区域相对保留。在这里，我们旨在基于替代神经影像学标志物来了解 bvAD 的临床解剖分离。
方法
我们回顾性纳入了 150 名参与者，包括 29 名 bvAD、28 名“典型”遗忘型为主的 AD（tAD）、28 名行为变异型额颞叶痴呆（bvFTD）和 65 名认知正常的参与者。将 bvAD 患者与其他诊断组进行比较，比较指标包括 [F]FDG-PET 测量的葡萄糖代谢和代谢连接，以及 MRI 测量的皮质下灰质和白质高信号（WMH）体积。进行了Receiver-Operating-Characteristic 分析，以确定具有最高诊断准确性的神经影像学测量值。
结果
bvAD 和 tAD 与对照组相比表现出主要的颞顶叶代谢低下，并且在直接对比中没有差异。然而，在患者与对照组之间的对比的统计映射上叠加显示，bvAD 的额岛叶代谢低下更为广泛，部分与 bvFTD 重叠。与 tAD 相比，bvAD 表现出更大的前默认模式网络（DMN）参与，类似于 bvFTD，并且后扣带回皮质与前额区域的连接减少。WMH 和皮质下体积的分析表明，bvAD 与 tAD 的相似性大于与 bvFTD 的相似性，bvAD 的杏仁核体积大于 tAD。用于区分 bvAD 与 bvFTD 的前三名鉴别指标是 FDG 后 DMN 比（bvAD<bvFTD）、MRI 后 DMN 比（bvAD<bvFTD）、MRI 突显网络比（bvAD>bvFTD，曲线下面积 [AUC]范围 0.85-0.91，均 p<0.001）。用于区分 bvAD 与 tAD 的前三名鉴别指标是杏仁核体积（bvAD>tAD）、MRI 前 DMN 比（bvAD<tAD）、FDG 前 DMN 比（bvAD<tAD，AUC 范围 0.71-0.84，均 p<0.05）。
结论
轻微的额岛叶代谢低下和前 DMN 参与可能是 bvAD 突出行为表型的基础。
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