Heleen Vanhaute1, Jenny Ceccarini2, Laura Michiels2, Michel Koole2, Stefan Sunaert2, Robin Lemmens2, Eric Triau2, Louise Emsell2, Mathieu Vandenbulcke2, Koen Van Laere2. 1. 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. koen.vanlaere@uzleuven.be. 2. 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.
Abstract
OBJECTIVE: 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). METHODS: In this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11C-UCB-J (synaptic vesicle protein 2A), 18F-MK-6240 (tau deposition), and 11C-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 18F-MK-6240 and 11C-UCB-J binding with cognitive performance. RESULTS: Compared to controls, patients with aMCI showed a decreased 11C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%-51%, p cluster = 0.02). Increased 18F-MK6240 binding in the same region was observed (42%-44%, p cluster = 0.0003), spreading to association cortices. In the MTL, higher 18F-MK-6240 binding inversely related to lower 11C-UCB-J binding (p = 0.02, r = -0.76). Decreased performance on cognitive tests was associated with both increased 18F-MK-6240 and decreased 11C-UCB-J binding in the hippocampus (p < 0.01, r > 0.7), although in a multivariate analysis only 18F-MK-6240 binding was significantly related to cognitive performance. CONCLUSIONS: 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.
OBJECTIVE: 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). METHODS: In this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11C-UCB-J (synaptic vesicle protein 2A), 18F-MK-6240 (tau deposition), and 11C-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 18F-MK-6240 and 11C-UCB-J binding with cognitive performance. RESULTS: Compared to controls, patients with aMCI showed a decreased 11C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%-51%, p cluster = 0.02). Increased 18F-MK6240 binding in the same region was observed (42%-44%, p cluster = 0.0003), spreading to association cortices. In the MTL, higher 18F-MK-6240 binding inversely related to lower 11C-UCB-J binding (p = 0.02, r = -0.76). Decreased performance on cognitive tests was associated with both increased 18F-MK-6240 and decreased 11C-UCB-J binding in the hippocampus (p < 0.01, r > 0.7), although in a multivariate analysis only 18F-MK-6240 binding was significantly related to cognitive performance. CONCLUSIONS: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.
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