Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Neuroscience Center, Samsung Medical Center, Seoul, South Korea.
Eur J Nucl Med Mol Imaging. 2018 Dec;45(13):2368-2376. doi: 10.1007/s00259-018-4081-5. Epub 2018 Jul 6.
We estimated whether amyloid involvement in subcortical regions may predict cognitive impairment, and established an amyloid staging scheme based on degree of subcortical amyloid involvement.
Data from 240 cognitively normal older individuals, 393 participants with mild cognitive impairment, and 126 participants with Alzheimer disease were acquired at Alzheimer's Disease Neuroimaging Initiative sites. To assess subcortical involvement, we analyzed amyloid deposition in amygdala, putamen, and caudate nucleus. We staged participants into a 3-stage model based on cortical and subcortical amyloid involvement: 382 with no cortical or subcortical involvement as stage 0, 165 with cortical but no subcortical involvement as stage 1, and 203 with both cortical and subcortical involvement as stage 2.
Amyloid accumulation was first observed in cortical regions and spread down to the putamen, caudate nucleus, and amygdala. In longitudinal analysis, changes in MMSE, ADAS-cog 13, FDG PET SUVR, and hippocampal volumes were steepest in stage 2 followed by stage 1 then stage 0 (p value <0.001). Stage 2 showed steeper changes in MMSE score (β [SE] = -0.02 [0.004], p < 0.001), ADAS-cog 13 (0.05 [0.01], p < 0.001), FDG PET SUVR (-0.0008 [0.0003], p = 0.004), and hippocampal volumes (-4.46 [0.65], p < 0.001) compared to stage 1.
We demonstrated a downward spreading pattern of amyloid, suggesting that amyloid accumulates first in neocortex followed by subcortical structures. Furthermore, our new finding suggested that an amyloid staging scheme based on subcortical involvement might reveal how differential regional accumulation of amyloid affects cognitive decline through functional and structural changes of the brain.
我们评估了皮质下区域的淀粉样蛋白沉积是否可以预测认知障碍，并建立了一个基于皮质下淀粉样蛋白沉积程度的淀粉样蛋白分期方案。
在阿尔茨海默病神经影像学倡议的研究点获取了 240 名认知正常的老年人、393 名轻度认知障碍患者和 126 名阿尔茨海默病患者的数据。为了评估皮质下受累情况，我们分析了杏仁核、壳核和尾状核的淀粉样蛋白沉积。我们根据皮质和皮质下淀粉样蛋白受累情况将参与者分为 3 期模型：382 名无皮质或皮质下受累为 0 期，165 名有皮质受累但无皮质下受累为 1 期，203 名有皮质和皮质下受累为 2 期。
淀粉样蛋白首先在皮质区域积累，并向下扩散到壳核、尾状核和杏仁核。在纵向分析中，MMSE、ADAS-cog13、FDG PET SUVR 和海马体积的变化在 2 期最快，其次是 1 期，然后是 0 期（p 值<0.001）。2 期 MMSE 评分（β[SE] =-0.02[0.004]，p<0.001）、ADAS-cog13（0.05[0.01]，p<0.001）、FDG PET SUVR（-0.0008[0.0003]，p=0.004）和海马体积（-4.46[0.65]，p<0.001）的变化幅度均大于 1 期。
我们证明了淀粉样蛋白的向下扩散模式，表明淀粉样蛋白首先在新皮质积累，然后在皮质下结构积累。此外，我们的新发现表明，基于皮质下受累的淀粉样蛋白分期方案可能通过大脑的功能和结构变化揭示淀粉样蛋白的差异区域积累如何影响认知下降。
