Vita-Salute San Raffaele University, Milan, Italy.
In vivo human molecular and structural neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Alzheimers Dis. 2021;80(1):433-445. doi: 10.3233/JAD-201351.
Mild cognitive impairment (MCI) is a transitional condition between normal cognition and dementia. [18F]FDG-PET reveals brain hypometabolism patterns reflecting neuronal/synaptic dysfunction, already in the prodromal MCI phase. Activated microglia is part of the pathogenetic processes leading to neurodegeneration.
Using [11C]-(R)-PK11195 and [18F]FDG-PET, we aimed to in vivo investigate the presence of microglial activation, and the relationship with brain glucose metabolism, in single MCI subjects.
Eight MCI subjects underwent both [18F]FDG-PET and [11C]-(R)-PK11195 PET. We used validated quantification methods to obtain brain hypometabolism maps and microglia activation peaks in single subjects. We investigated both the spatial overlap and the relationship between brain glucose hypometabolism and microglia activation, by means of Dice similarity coefficient and using Pearson's correlation at single subject level.
Each MCI showed a specific brain hypometabolism pattern indicative of different possible etiologies, as expected in MCI population (i.e., Alzheimer's disease-like, frontotemporal dementia-like, hippocampal-type, normal aging type). [11C]-(R)-PK11195 PET analysis revealed a spatial concordance with regional hypometabolism in all subjects with several clusters of significant microglia activation showing an inverse correlation with the regional metabolism. This was proportional to the strength of between-signals correlation coefficient (β = -0.804; p = 0.016).
Microglia activation is present in the prodromal MCI phase of different underlying etiologies, showing spatial concordance and inverse correlation with brain glucose metabolism at single-subject level. These findings suggest a possible contribution of activated microglia to neurodegeneration, showing important implications for local immune activity in the early neurodegenerative processes.
轻度认知障碍（MCI）是正常认知与痴呆之间的过渡状态。[18F]FDG-PET 显示出反映神经元/突触功能障碍的脑代谢低下模式，在前驱期 MCI 阶段已经存在。激活的小胶质细胞是导致神经退行性变的发病机制过程的一部分。
使用[11C]-(R)-PK11195 和[18F]FDG-PET，我们旨在对单个 MCI 患者体内的小胶质细胞激活的存在及其与脑葡萄糖代谢的关系进行研究。
8 名 MCI 患者接受了[18F]FDG-PET 和[11C]-(R)-PK11195 PET 检查。我们使用经过验证的量化方法，在单个患者中获得脑代谢低下图和小胶质细胞激活峰值。我们通过 Dice 相似系数和在单个患者水平上使用 Pearson 相关性，分别研究了脑葡萄糖代谢低下和小胶质细胞激活之间的空间重叠和关系。
每个 MCI 患者均表现出特定的脑代谢低下模式，提示存在不同的可能病因，这在 MCI 患者中是预期的（即阿尔茨海默病样、额颞叶痴呆样、海马型、正常老化型）。[11C]-(R)-PK11195 PET 分析显示，在所有患者中均存在与区域性代谢低下具有空间一致性的小胶质细胞激活，并且多个小胶质细胞激活簇与区域代谢呈负相关。这与信号之间相关性系数（β=-0.804；p=0.016）的强度成正比。
在不同潜在病因的前驱期 MCI 阶段存在小胶质细胞激活，在单个患者水平上表现出与脑葡萄糖代谢的空间一致性和负相关性。这些发现提示激活的小胶质细胞可能对神经退行性变有贡献，这对早期神经退行性过程中的局部免疫活性具有重要意义。
