Department of Neurology, University Hospital Cologne, 50937 Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, 52425 Jülich, Germany; Max-Planck-Institute for Metabolism Research, 50937 Cologne, Germany.
Department of Neurology, University Hospital Cologne, 50937 Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, 52425 Jülich, Germany.
Neuroimage Clin. 2019;24:101978. doi: 10.1016/j.nicl.2019.101978. Epub 2019 Aug 9.
Elucidating the relationship between neuronal metabolism and the integrity of the cholinergic system is prerequisite for a profound understanding of cholinergic dysfunction in Alzheimer's disease. The cholinergic system can be investigated specifically using positron emission tomography (PET) with [C]N-methyl-4-piperidyl-acetate (MP4A), while neuronal metabolism is often assessed with 2-deoxy-2-[F]fluoro-d-glucose-(FDG) PET. We hypothesised a close correlation between MP4A-perfusion and FDG-uptake, permitting inferences about metabolism from MP4A-perfusion, and investigated the patterns of neuronal hypometabolism and cholinergic impairment in non-demented AD patients. MP4A-PET was performed in 18 cognitively normal adults and 19 patients with mild cognitive impairment (MCI) and positive AD biomarkers. In nine patients with additional FDG-PET, the sum images of every combination of consecutive early MP4A-frames were correlated with FDG-scans to determine the optimal time window for assessing MP4A-perfusion. Acetylcholinesterase (AChE) activity was estimated using a 3-compartmental model. Group comparisons of MP4A-perfusion and AChE-activity were performed using the entire sample. The highest correlation between MP4A-perfusion and FDG-uptake across the cerebral cortex was observed 60-450 s after injection (r = 0.867). The patterns of hypometabolism (FDG-PET) and hypoperfusion (MP4A-PET) in MCI covered areas known to be hypometabolic early in AD, while AChE activity was mainly reduced in the lateral temporal cortex and the occipital lobe, sparing posterior midline structures. Data indicate that patterns of cholinergic impairment and neuronal hypometabolism differ significantly at the stage of MCI in AD, implying distinct underlying pathologies, and suggesting potential predictors of the response to cholinergic pharmacotherapy.
阐明神经元代谢与胆碱能系统完整性之间的关系是深入了解阿尔茨海默病中胆碱能功能障碍的前提。可以使用 [C]N-甲基-4-哌啶基-乙酸酯（MP4A）的正电子发射断层扫描（PET）来专门研究胆碱能系统，而神经元代谢通常使用 2-脱氧-2-[F]氟代-d-葡萄糖（FDG）PET 来评估。我们假设 MP4A 灌注与 FDG 摄取之间存在密切相关性，允许从 MP4A 灌注推断代谢情况，并研究非痴呆 AD 患者的神经元代谢低下和胆碱能损伤模式。对 18 名认知正常的成年人和 19 名轻度认知障碍（MCI）和阳性 AD 生物标志物的患者进行了 MP4A-PET。在另外 9 名有 FDG-PET 的患者中，对每个连续早期 MP4A 帧的组合的总和图像与 FDG 扫描相关联，以确定评估 MP4A 灌注的最佳时间窗口。使用三房室模型估计乙酰胆碱酯酶（AChE）活性。使用整个样本对 MP4A 灌注和 AChE 活性进行组间比较。在整个大脑皮层中，MP4A 灌注与 FDG 摄取之间的相关性最高，在注射后 60-450s 观察到（r=0.867）。MCI 中的代谢低下（FDG-PET）和灌注低下（MP4A-PET）模式覆盖了 AD 早期代谢低下的区域，而 AChE 活性主要在外侧颞叶和枕叶减少，中线后结构不受影响。数据表明，AD 患者在 MCI 阶段的胆碱能损伤和神经元代谢低下模式存在显著差异，暗示了不同的潜在病理，并表明对胆碱能药物治疗反应的潜在预测因子。
