ORCID Profile
0000-0001-5200-7245
Current Organisations
KU Leuven
,
Ghent Univerity
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-06-2020
DOI: 10.1212/WNL.0000000000009818
Abstract: 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 11 C-UCB-J (synaptic vesicle protein 2A), 18 F-MK-6240 (tau deposition), and 11 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 18 F-MK-6240 and 11 C-UCB-J binding with cognitive performance. 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 hippoc us ( p 0.01, r 0.7), although in a multivariate analysis only 18 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.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2021
DOI: 10.1101/2021.02.08.21251205
Abstract: MRI derived hippoc al volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer’s Disease (AD). Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants. Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid. Both HV(χ 2 (1) = 6.46: p= 0.011) and amyloid (χ 2 (1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). Hippoc al volume may be a useful gatekeeper for identifying depressed in iduals at risk for AD who would benefit from additional amyloid biomarkers when available.
Publisher: Wiley
Date: 13-08-2023
DOI: 10.1002/MDS.29570
Abstract: To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain. Normal aging is associated with a decline in movement quality and quantity, commonly termed “mild parkinsonian signs” or more recently MMS. Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand 11 C‐UCB‐J allows the investigation of brain‐motor associations at the synaptic level in vivo. Fifty‐eight healthy older adults (≥50 years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and 11 C‐UCB‐J PET data were available in 54 participants. 11 C‐UCB‐J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates. Participants (68 ± 7.5 years 52% female) had an average MDS‐UPDRS part III score of 3.3 ± 2.8. The MDS‐UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f 2 showed moderate effect sizes for subcortical (range, 0.30–0.35), cortical (0.28–0.35) and cerebellar VOIs (0.31). MMS in healthy aging are associated with lower synaptic density throughout the brain. © 2023 International Parkinson and Movement Disorder Society.
No related grants have been discovered for Koen Van Laere.