Journal
NEUROLOGY
Volume 95, Issue 5, Pages E545-E553Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000009818
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Funding
- Research Foundation Flanders (FWO) [FWO/G093218N]
- KU Leuven Internal C2 funding [C24-17-063]
- Foundation for Alzheimer's Research Flanders (Stichting Alzheimer Onderzoek) [SAO-FRA 20190019]
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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(11)C-UCB-J (synaptic vesicle protein 2A),F-18-MK-6240 (tau deposition), and(11)C-Pittsburgh compound B (beta-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(18)F-MK-6240 and(11)C-UCB-J binding with cognitive performance. Results Compared to controls, patients with aMCI showed a decreased(11)C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%-51%,p(cluster)= 0.02). Increased(18)F-MK6240 binding in the same region was observed (42%-44%,p(cluster)= 0.0003), spreading to association cortices. In the MTL, higher(18)F-MK-6240 binding inversely related to lower(11)C-UCB-J binding (p= 0.02,r= -0.76). Decreased performance on cognitive tests was associated with both increased(18)F-MK-6240 and decreased(11)C-UCB-J binding in the hippocampus (p< 0.01,r> 0.7), although in a multivariate analysis only(18)F-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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