van-Laar, T. (Teus)
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- Abnormal pattern of brain glucose metabolism in parkinson’s disease: replication in three european cohorts(Springer, 2020) Leenders, K.L. (Klaus L.); Pagani, M. (Marco); Nobili, F. (Flavio); Renken, R.J. (Remco J.); Obeso, J.A. (José A.); Teune, L.K. (L. K.); Arnaldi, D. (Dario); Morbelli, S. (Silvia); van-Laar, T. (Teus); Meles, S.K. (Sanne K.); Rodriguez-Oroz, M.C. (María Cruz)Rationale In Parkinson’s disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP). Methods The PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 “de-novo” PD patients from an Italian cohort. A further 24 controls and 18 “de-novo” Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy. Results A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in “de-novo” PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA.
- Cerebral topography of vesicular cholinergic transporter changes in neurologically intact adults: A [18F]FEOBV PET study(Elsevier, 2022) Kanel, P. (Prabesh); van-der-Zee, S. (Sygrid); Sanchez-Catasus, C.A. (Carlos A.); Koeppe, R.A. (Robert A.); Scott, P.J.H. (Peter J. H.); van-Laar, T. (Teus); Albin, R.L. (Roger L.); Bohnen, N. (Nico)Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common in several neurodegenerative disorders. We describe age-related declines of regional cholinergic neuron terminal density in vivo using the positron emission tomography (PET) ligand [18F](–)5-Fluoroethoxybenzovesamicol ([18F]FEOBV), a vesamicol analogue selectively binding to the vesicular acetylcholine transporter (VAChT). A total of 42 subjects without clinical evidence of neurologic disease (mean 50.55 [range 20–80] years, 24 Male/18 Female) underwent [18F]FEOBV brain PET imaging. We used SPM based voxel-wise statistical analysis to perform whole brain voxel-based parametric analysis (family-wise error corrected, FWE) and to also extract the most significant clusters of regions correlating with aging with gender as nuisance variable. Age-related VAChT binding reductions were found in primary sensorimotor cortex, visual cortex, caudate nucleus, anterior to mid-cingulum, bilateral insula, para-hippocampus, hippocampus, anterior temporal lobes/amygdala, dorsomedial thalamus, metathalamus, and cerebellum (gender and FWE-corrected, P < 0.05). These findings show a specific topographic pattern of regional vulnerability of cholinergic nerve terminals across multiple cholinergic systems accompanying aging.