From the Division of Nuclear Medicine (H.V., J.C., M.K., K.V.L.) and Department of Neurology (L.M., R.L.), University Hospitals Leuven; Nuclear Medicine and Molecular Imaging (H.V., J.C., M.K., S.S., L.E., K.V.L.) and Translational MRI (S.S., L.E.), Department of Imaging and Pathology, and Department of Geriatric Psychiatry (H.V., L.E., M.V.), University Psychiatric Centre, Laboratory for Neurobiology (L.M., R.L.), KU Leuven; and Center for Brain and Disease Research (L.M., R.L.), VIB-KU Leuven, Belgium. Dr. Triau is in private practice in Leuven, Belgium.
Neurology. 2020 Aug 4;95(5):e545-e553. doi: 10.1212/WNL.0000000000009818. Epub 2020 Jun 3.
To investigate in vivo whether synaptic loss and neurofibrillary tangle load spatially overlap and correlate with clinical symptoms in patients with amnestic mild cognitive impairment (aMCI).
In this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with C-UCB-J (synaptic vesicle protein 2A), F-MK-6240 (tau deposition), and C-Pittsburgh compound B (β-amyloid) and neuropsychological assessment. Gray matter atrophy was assessed by voxel-based morphometry with T1-weighted MRIs. Voxel-wise and volume-of-interest analyses were conducted on PET data. The interrelationship of synaptic density and tau deposition was investigated. We also investigated correlations of F-MK-6240 and C-UCB-J binding with cognitive performance.
Compared to controls, patients with aMCI showed a decreased C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%-51%, = 0.02). Increased F-MK6240 binding in the same region was observed (42%-44%, = 0.0003), spreading to association cortices. In the MTL, higher F-MK-6240 binding inversely related to lower C-UCB-J binding ( = 0.02, = -0.76). Decreased performance on cognitive tests was associated with both increased F-MK-6240 and decreased C-UCB-J binding in the hippocampus ( < 0.01, > 0.7), although in a multivariate analysis only F-MK-6240 binding was significantly related to cognitive performance.
Patients with aMCI have high tau deposition and synaptic density loss mainly in key regions known to be involved in early cognitive impairment, indicating that these are interrelated in the MTL, while tau binding had already spread toward association cortices. Longitudinal data are needed to provide further insight into the temporal aspects of this relationship.
研究遗忘型轻度认知障碍（aMCI）患者体内的突触丢失和神经纤维缠结负荷是否在空间上重叠，并与临床症状相关。
在这项横断面研究中，10 名 aMCI 患者和 10 名健康对照者接受了 C-UCB-J（突触小泡蛋白 2A）、F-MK-6240（tau 沉积）和 C-Pittsburgh 化合物 B（β-淀粉样蛋白）的三联 PET-MRI 检查，并进行了神经心理学评估。通过 T1 加权 MRI 进行基于体素的形态测量学评估灰质萎缩。对 PET 数据进行体素和感兴趣区分析。研究了突触密度和 tau 沉积之间的相互关系。我们还研究了 F-MK-6240 和 C-UCB-J 结合与认知表现的相关性。
与对照组相比，aMCI 患者的 C-UCB-J 结合主要在内侧颞叶（MTL；48%-51%， = 0.02）的亚结构中减少。观察到同一区域的 F-MK6240 结合增加（42%-44%， = 0.0003），并扩散到联合皮质。在 MTL 中，较高的 F-MK-6240 结合与较低的 C-UCB-J 结合呈负相关（ = 0.02， = -0.76）。在海马体中，认知测试表现下降与 F-MK-6240 增加和 C-UCB-J 结合减少均相关（ < 0.01， > 0.7），尽管在多变量分析中，只有 F-MK-6240 结合与认知表现显著相关。
aMCI 患者的 tau 沉积和突触密度丢失主要发生在已知与早期认知障碍相关的关键区域，表明这些区域在 MTL 中相互关联，而 tau 结合已经扩散到联合皮质。需要进行纵向研究以进一步深入了解这种关系的时间方面。
