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11. Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial

Author

Ramaswami, Uma, Bichet, Daniel G., Clarke, Lorne A., Dostalova, Gabriela, Fainboim, Alejandro, Fellgiebel, Andreas, Forcelini, Cassiano M., An Haack, Kristina, Hopkin, Robert J., Mauer, Michael, Najafian, Behzad, Scott, C. Ronald, Shankar, Suma P., Thurberg, Beth L., Tøndel, Camilla, Tylki-Szymanska, Anna, Bénichou, Bernard, and Wijburg, Frits A.

Published
2019
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13. The EADC‐ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Frisoni, Giovanni B, Jack, Clifford R, Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S, Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J, Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G, Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G, deToledo‐Morrell, Leyla, Geerlings, Mirjam I, Kaye, Jeffrey, Killiany, Ronald J, Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C, Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C, Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, Boccardi, Marina, Initiative, EADC‐ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging, Albert, Marilyn S, Bennet, David, Camicioli, Richard, Collins, D Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J, Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M, Visser, Peter‐Jelle, Wahlund, Lars‐Olof, Weiner, Michael W, and Winblad, Bengt

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biomedical Imaging, Neurodegenerative, Clinical Research, Brain Disorders, Acquired Cognitive Impairment, Bioengineering, Aged, Alzheimer Disease, Atrophy, Female, Functional Laterality, Hippocampus, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Internet, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Organ Size, Reproducibility of Results, Hippocampal volumetry, Magnetic resonance, Alzheimer's disease, Biomarkers, Diagnostic criteria, Enrichment, Clinical trials, Validation, Harmonized protocol, Standard operating procedures, Manual segmentation, EADC-ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).ConclusionsThe HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Published
2015

14. Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Author

Wijburg, Frits A, Bénichou, Bernard, Bichet, Daniel G, Clarke, Lorne A, Dostalova, Gabriela, Fainboim, Alejandro, Fellgiebel, Andreas, Forcelini, Cassiano, Haack, Kristina An, Hopkin, Robert J, Mauer, Michael, Najafian, Behzad, Scott, C Ronald, Shankar, Suma P, Thurberg, Beth L, Tøndel, Camilla, Tylki-Szymańska, Anna, and Ramaswami, Uma

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Rare Diseases, Clinical Research, Prevention, Pediatric, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Renal and urogenital, Adolescent, Biopsy, Brain, Child, Child, Preschool, Demography, Endothelium, Vascular, Fabry Disease, Genotype, Glomerular Filtration Rate, Glycolipids, Humans, Iohexol, Kidney, Male, Mutation, Quality of Life, Skin, Sphingolipids, Trihexosylceramides, General Science & Technology
Abstract

Trial designThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13-17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0 mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial registrationClinicalTrials.gov NCT00701415.

Published
2015

15. Subregional Basal Forebrain Atrophy in Alzheimer's Disease: A Multicenter Study

Author

Kilimann, Ingo, Grothe, Michel, Heinsen, Helmut, Alho, Eduardo Joaquim Lopez, Grinberg, Lea, Amaro, Edson, Dos Santos, Gláucia Aparecida Bento, da Silva, Rafael Emídio, Mitchell, Alex J, Frisoni, Giovanni B, Bokde, Arun LW, Fellgiebel, Andreas, Filippi, Massimo, Hampel, Harald, Klöppel, Stefan, and Teipel, Stefan J

Subjects
Alzheimer's Disease, Neurodegenerative, Acquired Cognitive Impairment, Biomedical Imaging, Neurosciences, Aging, Dementia, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Atrophy, Basal Forebrain, Cognitive Dysfunction, Female, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Postmortem Changes, biomarker, cholinergic system, dementia, European DTI Study on Dementia, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD.

Published
2014

19. The European DTI Study on Dementia — A multicenter DTI and MRI study on Alzheimer's disease and Mild Cognitive Impairment

Author

Brueggen, Katharina, Grothe, Michel J., Dyrba, Martin, Fellgiebel, Andreas, Fischer, Florian, Filippi, Massimo, Agosta, Federica, Nestor, Peter, Meisenzahl, Eva, Blautzik, Janusch, Frölich, Lutz, Hausner, Lucrezia, Bokde, Arun L.W., Frisoni, Giovanni, Pievani, Michela, Klöppel, Stefan, Prvulovic, David, Barkhof, Frederik, Pouwels, Petra J.W., Schröder, Johannes, Hampel, Harald, Hauenstein, Karlheinz, and Teipel, Stefan

Published
2017
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22. 13 .Modellprojekte zur Versorgung

Author

Fellgiebel, Andreas, primary, Thyrian, Jochen René, additional, Michalowsky, Bernhard, additional, Wucherer, Diana, additional, Dreier-Wolfgramm, Adina, additional, Zwingmann, Ina, additional, and Hoffmann, Wolfgang, additional

Published
2018
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28. The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Albert, Marilyn S., Bennet, David, Camicioli, Richard, Collins, D. Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J., Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M., Visser, Peter-Jelle, Wahlund, Lars-Olof, Weiner, Michael W., Winblad, Bengt, Frisoni, Giovanni B., Jack, Clifford R., Jr., Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S., Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J., Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G., Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G., deToledo-Morrell, Leyla, Geerlings, Mirjam I., Kaye, Jeffrey, Killiany, Ronald J., Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C., Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C., Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, and Boccardi, Marina

Published
2015
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30. Harmonized benchmark labels of the hippocampus on magnetic resonance: The EADC-ADNI project

Author

Bartzokis, George, DeCarli, Charles, deToledo-Morrell, Leyla, Fellgiebel, Andreas, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Killiany, Ronald J., Malykhin, Nikolai, Pruessner, Jens C., Soininen, Hilkka, Wang, Lei, Watson, Craig, Wolf, Henrike, Bocchetta, Martina, Boccardi, Marina, Ganzola, Rossana, Apostolova, Liana G., Preboske, Gregory, Wolf, Dominik, Ferrari, Clarissa, Pasqualetti, Patrizio, Robitaille, Nicolas, Duchesne, Simon, Jack, Clifford R., Jr., and Frisoni, Giovanni B.

Published
2015
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32. Combining DTI and MRI for the Automated Detection of Alzheimer’s Disease Using a Large European Multicenter Dataset

Author

Dyrba, Martin, Ewers, Michael, Wegrzyn, Martin, Kilimann, Ingo, Plant, Claudia, Oswald, Annahita, Meindl, Thomas, Pievani, Michela, Bokde, Arun L. W., Fellgiebel, Andreas, Filippi, Massimo, Hampel, Harald, Klöppel, Stefan, Hauenstein, Karlheinz, Kirste, Thomas, Teipel, Stefan J., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Yap, Pew-Thian, editor, Liu, Tianming, editor, Shen, Dinggang, editor, Westin, Carl-Fredrik, editor, and Shen, Li, editor

Published
2012
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33. Apathy in patients with Alzheimer's disease is a cost‐driving factor

Author

Kruse, Christopher, primary, Maier, Franziska, additional, Spottke, Annika, additional, Bach, Jan‐Philipp, additional, Bartels, Claudia, additional, Buerger, Katharina, additional, Fellgiebel, Andreas, additional, Fliessbach, Klaus, additional, Frölich, Lutz, additional, Hausner, Lucrezia, additional, Hellmich, Martin, additional, Klöppel, Stefan, additional, Klostermann, Arne, additional, Kornhuber, Johannes, additional, Laske, Christoph, additional, Peters, Oliver, additional, Priller, Josef, additional, Richter‐Schmidinger, Tanja, additional, Schneider, Anja, additional, Shah‐Hosseini, Kija, additional, Teipel, Stefan, additional, von Arnim, Christine A. F., additional, Wiltfang, Jens, additional, van der Wurp, Hendrik, additional, Dodel, Richard, additional, and Jessen, Frank, additional

Published
2023
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35. Investigation of brain networks activity and their association with transfer of cognitive training gains

Author

Faraza, Sofia, Hergert, Lena, Riedel, David, Fellgiebel, Andreas, Teipel, Stefan, Dyrba, Martin, Wolf, Dominik, Fischer, Florian U, Knaepen, Kristel, Kollmann, Bianca, Tüscher, Oliver, Binder, Harald, and Mierau, Andreas

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, ddc:610, Neurology (clinical), Geriatrics and Gerontology
Abstract

Age-related cognitive decline increase the need for cognitive interventions to maintain cognitive function. Transfer of training gains to untrained tasks is a key indicator for the effectiveness of cognitive training. However, the underlying brain mechanisms need to be further investigated. We implemented a cognitive training study to assess functional connectivity determinants of transfer of training gains.MethodA sample of 181 healthy older adults (mean age: 68 years) underwent a 4-week cognitive training across three sites. The control group consisted of 54 older adults. To evaluate transfer and training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. The training group was divided in subjects who had and who did not have successful transfer, which was defined as higher improvement in cognitive tasks than the control group. We used cognitive scores representing working memory, verbal and visuospatial memory and executive functions. Baseline resting-state functional magnetic resonance imaging was assessed in order to investigate the functional connectivity of brain networks associated with cognitive functions.ResultCognitive performance of the training group remained stable across time and did not show a significant improvement. Transfer of training gains directly after the training was limited. However, our participants were able to maintain gains 12 weeks after the training. We hypothesized a higher functional connectivity of brain networks, such as Default Mode Network or the Executive Network, to be associated with successful transfer of cognitive gains. Investigation of brain networks activity and the association with transfer of training gains is currently ongoing and complete results will be presented at the conference.ConclusionTransfer of training gains in aging is possible, but it remains limited. Cognitively healthy older adults might not have major benefits from a 4-week cognitive training. Our results could help to identify healthy older adults who will most benefit from training and understand the brain mechanisms underlying transfer of cognitive gains.

Published
2022
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