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1,340 results on '"Höglinger, Günter"'

1. Statistical modeling to adjust for time trends in adaptive platform trials utilizing non-concurrent controls

Author

Krotka, Pavla, Posch, Martin, Gewily, Mohamed, Höglinger, Günter, and Roig, Marta Bofill

Subjects
Statistics - Methodology
Abstract

Utilizing non-concurrent controls in the analysis of late-entering experimental arms in platform trials has recently received considerable attention, both on academic and regulatory levels. While incorporating this data can lead to increased power and lower required sample sizes, it might also introduce bias to the effect estimators if temporal drifts are present in the trial. Aiming to mitigate the potential calendar time bias, we propose various frequentist model-based approaches that leverage the non-concurrent control data, while adjusting for time trends. One of the currently available frequentist models incorporates time as a categorical fixed effect, separating the duration of the trial into periods, defined as time intervals bounded by any treatment arm entering or leaving the platform. In this work, we propose two extensions of this model. First, we consider an alternative definition of the time covariate by dividing the trial into fixed-length calendar time intervals. Second, we propose alternative methods to adjust for time trends. In particular, we investigate adjusting for autocorrelated random effects to account for dependency between closer time intervals and employing spline regression to model time with a smooth polynomial function. We evaluate the performance of the proposed approaches in a simulation study and illustrate their use by means of a case study.

Published
2024

2. Efficiency of Multivariate Tests in Trials in Progressive Supranuclear Palsy

Author

Yousefi, Elham, Gewily, Mohamed, König, Franz, Höglinger, Günter, Hopfner, Franziska, Karlsson, Mats O., Ristl, Robin, Zehetmayer, Sonja, and Posch, Martin

Subjects
Statistics - Methodology
Abstract

Measuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as Progressive Supranuclear Palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes measured by the items of the Progressive Supranuclear Palsy Rating Scale (PSPRS). We consider several statistical approaches, including sum scores, as an FDA-recommended version of the PSPRS, multivariate tests, and analysis approaches based on multiple comparisons of the individual items. We propose two novel approaches which measure disease status based on Item Response Theory models. We assess the performance of these tests in an extensive simulation study and illustrate their use with a re-analysis of the ABBV-8E12 clinical trial. Furthermore, we discuss the impact of the FDA-recommended scoring of item scores on the power of the statistical tests. We find that classical approaches as the PSPRS sum score demonstrate moderate to high power when treatment effects are consistent across the individual items. The tests based on Item Response Theory models yield the highest power when the simulated data are generated from an IRT model. The multiple testing based approaches have a higher power in settings where the treatment effect is limited to certain domains or items. The FDA-recommended item rescoring tends to decrease the simulated power. The study shows that there is no one-size-fits-all testing procedure for evaluating treatment effects using PSPRS items; the optimal method varies based on the specific effect size patterns. The efficiency of the PSPRS sum score, while generally robust and straightforward to apply, varies depending on the effect sizes' patterns encountered and more powerful alternatives are available in specific settings. These findings can have important implications for the design of future clinical trials in PSP.

Published
2023

6. Neuroimaging biomarkers in the biological definition of Parkinson’s disease and dementia with Lewy bodies – EANM position on current state, unmet needs and future perspectives

Author

Brendel, Matthias, Guedj, Eric, Yakushev, Igor, Morbelli, Silvia, Höglinger, Günter U., Tolboom, Nelleke, Verger, Antoine, Albert, Nathalie L., Cecchin, Diego, Fernandez, Pablo Aguiar, Fraioli, Francesco, Traub-Weidinger, Tatjana, Van Weehaeghe, Donatienne, and Barthel, Henryk

Published
2024
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7. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Author

Chatterjee, Madhurima, Özdemir, Selcuk, Fritz, Christian, Möbius, Wiebke, Kleineidam, Luca, Mandelkow, Eckhard, Biernat, Jacek, Doğdu, Cem, Peters, Oliver, Cosma, Nicoleta Carmen, Wang, Xiao, Schneider, Luisa-Sophia, Priller, Josef, Spruth, Eike, Kühn, Andrea A., Krause, Patricia, Klockgether, Thomas, Vogt, Ina R., Kimmich, Okka, Spottke, Annika, Hoffmann, Daniel C., Fliessbach, Klaus, Miklitz, Carolin, McCormick, Cornelia, Weydt, Patrick, Falkenburger, Björn, Brandt, Moritz, Guenther, René, Dinter, Elisabeth, Wiltfang, Jens, Hansen, Niels, Bähr, Mathias, Zerr, Inga, Flöel, Agnes, Nestor, Peter J., Düzel, Emrah, Glanz, Wenzel, Incesoy, Enise, Bürger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris S., Hopfner, Franziska, Wagemann, Olivia, Levin, Johannes, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Prudlo, Johannes, Gasser, Thomas, Brockmann, Kathrin, Mengel, David, Zimmermann, Milan, Synofzik, Matthis, Wilke, Carlo, Selma-González, Judit, Turon-Sans, Janina, Santos-Santos, Miguel Angel, Alcolea, Daniel, Rubio-Guerra, Sara, Fortea, Juan, Carbayo, Álvaro, Lleó, Alberto, Rojas-García, Ricardo, Illán-Gala, Ignacio, Wagner, Michael, Frommann, Ingo, Roeske, Sandra, Bertram, Lucas, Heneka, Michael T., Brosseron, Frederic, Ramirez, Alfredo, Schmid, Matthias, Beschorner, Rudi, Halle, Annett, Herms, Jochen, Neumann, Manuela, Barthélemy, Nicolas R., Bateman, Randall J., Rizzu, Patrizia, Heutink, Peter, Dols-Icardo, Oriol, Höglinger, Günter, Hermann, Andreas, and Schneider, Anja

Published
2024
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8. Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies

Author

Ferschmann, Christian, Messerschmidt, Konstantin, Gnörich, Johannes, Barthel, Henryk, Marek, Ken, Palleis, Carla, Katzdobler, Sabrina, Stockbauer, Anna, Fietzek, Urban, Finze, Anika, Biechele, Gloria, Rumpf, Jost-Julian, Saur, Dorothee, Schroeter, Matthias L., Rullmann, Michael, Beyer, Leonie, Eckenweber, Florian, Wall, Stephan, Schildan, Andreas, Patt, Marianne, Stephens, Andrew, Classen, Joseph, Bartenstein, Peter, Seibyl, John, Franzmeier, Nicolai, Levin, Johannes, Höglinger, Günter U., Sabri, Osama, Brendel, Matthias, and Scheifele, Maximilian

Published
2024
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9. Assessment of [18F]PI-2620 Tau-PET Quantification via Non-Invasive Automatized Image Derived Input Function

Author

Meindl, Maria, Zatcepin, Artem, Gnörich, Johannes, Scheifele, Maximilian, Zaganjori, Mirlind, Groß, Mattes, Lindner, Simon, Schaefer, Rebecca, Simmet, Marcel, Roemer, Sebastian, Katzdobler, Sabrina, Levin, Johannes, Höglinger, Günter, Bischof, Ann-Cathrin, Barthel, Henryk, Sabri, Osama, Bartenstein, Peter, Saller, Thomas, Franzmeier, Nicolai, Ziegler, Sibylle, and Brendel, Matthias

Published
2024
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10. The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis

Author

Ye, Lan, Greten, Stephan, Wegner, Florian, Doll-Lee, Johanna, Krey, Lea, Heine, Johanne, Gandor, Florin, Vogel, Annemarie, Berger, Luise, Gruber, Doreen, Levin, Johannes, Katzdobler, Sabrina, Peters, Oliver, Dashti, Eman, Priller, Josef, Spruth, Eike Jakob, Kühn, Andrea A., Krause, Patricia, Spottke, Annika, Schneider, Anja, Beyle, Aline, Kimmich, Okka, Donix, Markus, Haussmann, Robert, Brandt, Moritz, Dinter, Elisabeth, Wiltfang, Jens, Schott, Björn H., Zerr, Inga, Bähr, Mathias, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Weidinger, Endy, Düzel, Emrah, Glanz, Wenzel, Teipel, Stefan, Kilimann, Ingo, Wurster, Isabel, Brockmann, Kathrin, Hoffmann, Daniel C., Klockgether, Thomas, Krause, Olaf, Heck, Johannes, Höglinger, Günter U., and Klietz, Martin

Published
2024
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12. Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission

Author

Stockbauer, Anna, Beyer, Leonie, Huber, Maria, Kreuzer, Annika, Palleis, Carla, Katzdobler, Sabrina, Rauchmann, Boris-Stephan, Morbelli, Silvia, Chincarini, Andrea, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Lathuilière, Aurélien, Lemstra, Afina W., van Berckel, Bart N. M., Pilotto, Andrea, Padovani, Alessandro, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Aarsland, Dag, Nobili, Flavio, Gross, Mattes, Vöglein, Jonathan, Perneczky, Robert, Pogarell, Oliver, Buerger, Katharina, Franzmeier, Nicolai, Danek, Adrian, Levin, Johannes, Höglinger, Günter U., Bartenstein, Peter, Cumming, Paul, Rominger, Axel, and Brendel, Matthias

Published
2024
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13. The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Author

Greten, Stephan, Wegner, Florian, Jensen, Ida, Krey, Lea, Rogozinski, Sophia, Fehring, Meret, Heine, Johanne, Doll-Lee, Johanna, Pötter-Nerger, Monika, Zeitzschel, Molly, Hagena, Keno, Pedrosa, David J., Eggers, Carsten, Bürk, Katrin, Trenkwalder, Claudia, Claus, Inga, Warnecke, Tobias, Süß, Patrick, Winkler, Jürgen, Gruber, Doreen, Gandor, Florin, Berg, Daniela, Paschen, Steffen, Classen, Joseph, Pinkhardt, Elmar H., Kassubek, Jan, Jost, Wolfgang H., Tönges, Lars, Kühn, Andrea A., Schwarz, Johannes, Peters, Oliver, Dashti, Eman, Priller, Josef, Spruth, Eike J., Krause, Patricia, Spottke, Annika, Schneider, Anja, Beyle, Aline, Kimmich, Okka, Donix, Markus, Haussmann, Robert, Brandt, Moritz, Dinter, Elisabeth, Wiltfang, Jens, Schott, Björn H., Zerr, Inga, Bähr, Mathias, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Weidinger, Endy, Levin, Johannes, Katzdobler, Sabrina, Düzel, Emrah, Glanz, Wenzel, Teipel, Stefan, Kilimann, Ingo, Prudlo, Johannes, Gasser, Thomas, Brockmann, Kathrin, Hoffmann, Daniel C., Klockgether, Thomas, Krause, Olaf, Heck, Johannes, Höglinger, Günter U., and Klietz, Martin

Published
2024
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16. Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies

Author

Finze, Anika, Biechele, Gloria, Rauchmann, Boris-Stephan, Franzmeier, Nicolai, Palleis, Carla, Katzdobler, Sabrina, Weidinger, Endy, Guersel, Selim, Schuster, Sebastian, Harris, Stefanie, Schmitt, Julia, Beyer, Leonie, Gnörich, Johannes, Lindner, Simon, Albert, Nathalie L., Wetzel, Christian H., Rupprecht, Rainer, Rominger, Axel, Danek, Adrian, Burow, Lena, Kurz, Carolin, Tato, Maia, Utecht, Julia, Papazov, Boris, Zaganjori, Mirlind, Trappmann, Lena-Katharina, Goldhardt, Oliver, Grimmer, Timo, Haeckert, Jan, Janowitz, Daniel, Buerger, Katharina, Keeser, Daniel, Stoecklein, Sophia, Dietrich, Olaf, Morenas-Rodriguez, Estrella, Barthel, Henryk, Sabri, Osama, Bartenstein, Peter, Simons, Mikael, Haass, Christian, Höglinger, Günter U., Levin, Johannes, Perneczky, Robert, and Brendel, Matthias

Published
2023
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17. Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.

Author

Hopfner, Franziska, Tietz, Anja, Ruf, Viktoria, Ross, Owen, Koga, Shunsuke, Dickson, Dennis, Aguzzi, Adriano, Attems, Johannes, Beach, Thomas, Beller, Allison, Cheshire, William, van Deerlin, Vivianna, Deuschl, Günther, Duyckaerts, Charles, Ellinghaus, David, Evsyukov, Valentin, Flanagan, Margaret, Franke, Andre, Frosch, Matthew, Gearing, Marla, Gelpi, Ellen, van Gerpen, Jay, Ghetti, Bernardino, Glass, Jonathan, Halliday, Glenda, Helbig, Ingo, Höllerhage, Matthias, Huitinga, Inge, Irwin, David, Keene, Dirk, Kovacs, Gabor, Lee, Edward, Levin, Johannes, Martí, Maria, Mackenzie, Ian, McKeith, Ian, Mclean, Catriona, Mollenhauer, Brit, Neumann, Manuela, Newell, Kathy, Pantelyat, Alex, Pendziwiat, Manuela, Peters, Annette, Molina Porcel, Laura, Rabano, Alberto, Matěj, Radoslav, Rajput, Alex, Rajput, Ali, Reimann, Regina, Scott, William, Selvackadunco, Sashika, Simuni, Tanya, Stadelmann, Christine, Svenningsson, Per, Thomas, Alan, Trenkwalder, Claudia, Troakes, Claire, Trojanowski, John, Uitti, Ryan, White, Charles, Wszolek, Zbigniew, Xie, Tao, Ximelis, Teresa, Yebenes, Justo, Müller, Ulrich, Schellenberg, Gerard, Herms, Jochen, Kuhlenbäumer, Gregor, Höglinger, Günter, Grinberg, Lea, Seeley, William, and Desplats, Paula

Subjects
ZIC1, ZIC4, autopsy-confirmed, genome-wide association study, multiple system atrophy, Autoantibodies, Autopsy, Genome-Wide Association Study, Humans, Multiple System Atrophy, Nerve Tissue Proteins, Olivopontocerebellar Atrophies, Striatonigral Degeneration, Transcription Factors, alpha-Synuclein
Abstract

BACKGROUND: Multiple System Atrophy is a rare neurodegenerative disease with alpha-synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome-wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. OBJECTIVE: Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy-confirmed cases. METHODS: We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). RESULTS: The most strongly disease-associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P-values below 5 × 10-6 , all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). INTERPRETATION: Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4-immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4-mediated vulnerability of neurons in Multiple System Atrophy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

21. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Author

Wenning, Gregor K, Stankovic, Iva, Vignatelli, Luca, Fanciulli, Alessandra, Calandra‐Buonaura, Giovanna, Seppi, Klaus, Palma, Jose‐Alberto, Meissner, Wassilios G, Krismer, Florian, Berg, Daniela, Cortelli, Pietro, Freeman, Roy, Halliday, Glenda, Höglinger, Günter, Lang, Anthony, Ling, Helen, Litvan, Irene, Low, Phillip, Miki, Yasuo, Panicker, Jalesh, Pellecchia, Maria Teresa, Quinn, Niall, Sakakibara, Ryuji, Stamelou, Maria, Tolosa, Eduardo, Tsuji, Shoji, Warner, Tom, Poewe, Werner, and Kaufmann, Horacio

Subjects
Neurosciences, Rare Diseases, Prevention, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Brain, Consensus, Humans, Magnetic Resonance Imaging, Multiple System Atrophy, Prospective Studies, multiple system atrophy, diagnostic criteria, diagnosis, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundThe second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.ObjectiveTo develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology.MethodsWe identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.ResultsThe criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.ConclusionsThis set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

23. Author Correction: Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial

Author

Dam, Tien, Boxer, Adam L., Golbe, Lawrence I., Höglinger, Günter U., Morris, Huw R., Litvan, Irene, Lang, Anthony E., Corvol, Jean-Christophe, Aiba, Ikuko, Grundman, Michael, Yang, Lili, Tidemann-Miller, Beth, Kupferman, Joseph, Harper, Kristine, Kamisoglu, Kubra, Wald, Michael J., Graham, Danielle L., Gedney, Liz, O’Gorman, John, and Haeberlein, Samantha Budd

Published
2023
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25. Tau deposition patterns are associated with functional connectivity in primary tauopathies

Author

Franzmeier, Nicolai, Brendel, Matthias, Beyer, Leonie, Slemann, Luna, Kovacs, Gabor G, Arzberger, Thomas, Kurz, Carolin, Respondek, Gesine, Lukic, Milica J, Biel, Davina, Rubinski, Anna, Frontzkowski, Lukas, Hummel, Selina, Müller, Andre, Finze, Anika, Palleis, Carla, Joseph, Emanuel, Weidinger, Endy, Katzdobler, Sabrina, Song, Mengmeng, Biechele, Gloria, Kern, Maike, Scheifele, Maximilian, Rauchmann, Boris-Stephan, Perneczky, Robert, Rullman, Michael, Patt, Marianne, Schildan, Andreas, Barthel, Henryk, Sabri, Osama, Rumpf, Jost J, Schroeter, Matthias L, Classen, Joseph, Villemagne, Victor, Seibyl, John, Stephens, Andrew W, Lee, Edward B, Coughlin, David G, Giese, Armin, Grossman, Murray, McMillan, Corey T, Gelpi, Ellen, Molina-Porcel, Laura, Compta, Yaroslau, van Swieten, John C, Laat, Laura Donker, Troakes, Claire, Al-Sarraj, Safa, Robinson, John L, Xie, Sharon X, Irwin, David J, Roeber, Sigrun, Herms, Jochen, Simons, Mikael, Bartenstein, Peter, Lee, Virginia M, Trojanowski, John Q, Levin, Johannes, Höglinger, Günter, and Ewers, Michael

Subjects
Biochemistry and Cell Biology, Biological Sciences, Acquired Cognitive Impairment, Rare Diseases, Brain Disorders, Pick's Disease, Alzheimer's Disease, Dementia, Frontotemporal Dementia (FTD), Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Aging, Alzheimer's Disease Related Dementias (ADRD), Biomedical Imaging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Brain, Humans, Magnetic Resonance Imaging, Supranuclear Palsy, Progressive, Tauopathies, tau Proteins
Abstract

Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2nd generation 18F-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96). We find that inter-regional connectivity is associated with higher inter-regional correlation of both tau-PET and post-mortem tau levels in 4-repeat tauopathies. In regional cell-type specific post-mortem tau assessments, this association is stronger for neuronal than for astroglial or oligodendroglial tau, suggesting that connectivity is primarily associated with neuronal tau accumulation. Using tau-PET we find further that patient-level tau patterns are associated with the connectivity of subcortical tau epicenters. Together, the current study provides combined in vivo tau-PET and histopathological evidence that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

Published
2022

26. Morbus Parkinson

Author

Höglinger, Günter, Seifert, Roland, Ludwig, Wolf-Dieter, editor, Mühlbauer, Bernd, editor, and Seifert, Roland, editor

Published
2023
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27. Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial.

Author

Dam, Tien, Boxer, Adam L, Golbe, Lawrence I, Höglinger, Günter U, Morris, Huw R, Litvan, Irene, Lang, Anthony E, Corvol, Jean-Christophe, Aiba, Ikuko, Grundman, Michael, Yang, Lili, Tidemann-Miller, Beth, Kupferman, Joseph, Harper, Kristine, Kamisoglu, Kubra, Wald, Michael J, Graham, Danielle L, Gedney, Liz, O'Gorman, John, Haeberlein, Samantha Budd, and PASSPORT Study Group

Subjects
PASSPORT Study Group, Humans, Pneumonia, Supranuclear Palsy, Progressive, tau Proteins, Treatment Outcome, Double-Blind Method, Aged, Female, Male, Antibodies, Monoclonal, Humanized, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Immunology, Medical and Health Sciences
Abstract

A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P

Published
2021

28. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

Author

Okubadejo, Njideka, Ojo, Oluwadamilola, Abiodun, Oladunni, Achoru, Charles, Agabi, Osigwe, Agulanna, Uchechi, Akinyemi, Rufus, Ali, Mohammed, Ani-Osheku, Ifeyinwa, Arigbodi, Ohwotemu, Bello, Abiodun, Erameh, Cyril, Farombi, Temitope, Fawale, Michael, Imarhiagbe, Frank, Iwuozo, Emmanuel, Komolafe, Morenikeji, Nwani, Paul, Nwazor, Ernest, Nyandaiti, Yakub, Obiabo, Yahaya, Odeniyi, Olanike, Odiase, Francis, Ojini, Francis, Onwuegbuzie, Gerald, Osaigbovo, Godwin, Osemwegie, Nosakhare, Oshinaike, Olajumoke, Otubogun, Folajimi, Oyakhire, Shyngle, Ozomma, Simon, Samuel, Sarah, Taiwo, Funmilola, Wahab, Kolawole, Zubair, Yusuf, Gams Massi, Daniel, Gueumekane Bila lamou, Eric, Njamnshi Nfor, Leonard, Magnerou, Mélanie Annick, Fogang Fogoum, Yannick, Shalash, Ali, El-FawaI, Hassan, Khedr, Eman, Fawi, Gharib, A. Eltantawi, Mohamed, Salama, Mohamed, El-Jaafary, Shaimaa, Hamed, Sharifa, Tafesse Mengesha, Abenet, Alemayehu Ayele, Biniyam, Melka Oda, Dereje, Zenebe Zewde, Yared, Debebe Gelan, Yohanesse, AkpaIu, Albert, Charway-Felli, Augustina, Stephen Sarfo, Fred, Adjei, Patrick, Obese, Vida, Bocoum, Abdoulaye, Koita, Abdou, Oumar Guinto, Cheick, Coulibaly, Toumany, Maiga, Youssoufa, Kone, Zaynab, Bell, Abiodun, Adebowale, Akintunde A., Akpekpe, John, lyagba, Alagoma, Wulgo, Ali Mohammed, Arabambi, Babawale, Agu, Christian, Dike, Franklin, Ishola, Ismail, Abiodun, Kehinde, Ekenze, Oluchi, Agabi Osigwe, Paul, Balarabe, Salisu, Abubakar, Sani, Williams, Uduak, Fall, Maouly, Mamadou Diop, Alassane, Hilaire Dominique, Ewodo Touna, Mochan, Andre, Modi, Girish, Dindayal, Saiesha, Ali Awadelkareem, Eman, Elsayed, Inas, Dahawi, Maha, Awadelkareem, Mosab Ali, Misbah, Sarah, Mushengez, Brighton, Kimambo, Henrika, Msango, Leonard, Adebayo, Philip, OKeng, Kigocha, Diekker, Marieke, URassa, Sarah, Gouider, Riadh, Ben Djebara, Mouna, Gargouri, Amina, Kacem, Imen, Nasri, Amina, Mrabet, Saloua, Sghaier, Ikram, Mkada, Imen, Atadzhanov, Masharip, Chishimba, Lorraine, Rizig, Mie, Jama, Fatumah, Okunoye, Olaitan, Hardy, John, Houlden, Henry, Singleton, Andrew, Nalls, Mike, Shamim, Ejaz, Jonas, Cabell, Williamson, Jared, Hall, Deborah A., Rosenbaum, Marc, Davis, Staci, Dean, Marissa, Cromer, Candace, Smith, Jenna, Ruffrage, Lauren, Richardson, Joseph, Sipma, Rebeka, Xie, Tao, Padmanaban, Manesh, Warren, Natalie, Mercado, Tomas, Disbrow, Elizabeth, Chauppeta, Brian, Thomas-Dean, Fermine, Toms, Jamie, Lofton, Katelyn, Rawls, Ashley, Rizer, Kyle, Black, Nieci, Solle, Justin, O'Grady, Alyssa, Sherer, Todd, Fiske, Brian, Başak, A. Nazlı, Tan, Ai Huey, Noyce, Alastair, Akpalu, Albert, Espay, Alberto, Martínez-Carrasco, Alejandro, Medina, Alex, Zimprich, Alexander, Brice, Alexis, Karimova, Altynay, Hernandez, Alvaro, Illarionova, Anastasia, Quattrone, Andrea, Singleton, Andrew B, Sobering, Andrew K., Vinuela, Angel, Sanyaolu, Arinola, Schumacher-Schuh, Artur F., Kishore, Asha, Ahmad-Annuar, Azlina, Al Mubarak, Bashayer, Tang, Beisha, Pizarro Galleguillos, Benjamin, Jeon, Beomseok, Siddiqi, Bernadette, Casey, Bradford, Mollenhauer, Brit, Carroll, Camille, Rieder, Carlos, Pantazis, Caroline B., Comart, Charisse, Lin, Chin-Hsien, Klein, Christine, Bale, Claire, Shepherd, Claire E, Wegel, Claire, Blauwendraat, Cornelis, Vitale, Dan, Martinez-Ramirez, Daniel, Hall, Deborah, Hernandez, Dena, KP, Divya, Nguyen, Duan, Fon, Edward A., Dadiotis, Efthymios, Riley, Ekemini, Iakovenko, Elena, Stafford, Ellie, Gatto, Emilia M, Valente, Enza Maria, Vollstedt, Eva-Juliane, Faghri, Faraz, Genc, Gencer, Xiromerisiou, Georgia, Hadjigorgiou, Georgios, Hiu-Fai Chan, Germaine, Arboleda, Gonzalo, Kaishibayeva, Gulnaz, Höglinger, Günter, Leonard, Hampton, Madoev, Harutyun, Iwaki, Hirotaka, Chen, Honglei, Wu, Hsiu-Chuan, Shang, Huifang, Morris, Huw R, F. Mata, Ignacio, Keller Sarmiento, Ignacio Juan, Dagklis, Ioannis, Tarnanas, Ioannis, Aasly, Jan O., Hoenicka, Janet, Corvol, Jean-Christophe, Foo, Jia Nee, Guo, Jifeng, Junker, Johanna, Carr, Jonathan, Kim, Jonggeol Jeff, Orozco, Jorge, Jankovic, Joseph, Shulman, Joshua, Hunter, Julie, Solle, Justin C., Murphy, Kaileigh, Nuytemans, Karen, Kieburtz, Karl, Lohmann, Katja, Marek, Kenneth, Mok, Kin Ying, Kumar, Kishore, Levine, Kristin, Chahine, Lana M., Lange, Lara M., Pihlstrøm, Lasse, Screven, Laurel, Stefanis, Leonidas, Shulman, Lisa, Marsili, Luca, Parnetti, Lucilla, Kuhl, Maggie, Funayama, Manabu, Sharma, Manu, Tan, Manuela, Kauffman, Marcelo, Miranda, Marcelo, Bustamante, Maria Leonor, Stamelou, Maria, Periñan Tocino, Maria Teresa, Cornejo-Olivas, Mario, Jimenez del Rio, Marlene, Makarious, Mary B, Koretsky, Mathew, Rodriguez-Violante, Mayela, Ellis, Melina, Avenali, Micol, Rentería, Miguel E., Inca-Martines, Miguel z, Nalls, Mike A., Ibrahim Norlinah, Mohamed, Umair, Muhammad, Ip, Nancy, Louie, Naomi, Cheung, Nelson Yuk-Fai, Mencacci, Niccolò Emanuele, Wood, Nicholas, Williams, Nigel, Hattori, Nobutaka, Abdul Murad, Nor Azian, Ibrahim, Norlinah Mohamed, Monchi, Oury, Öztop Çakmak, Özgür, Öztop Çakmak, Patricio Öztop Çakmak, Lewis, Patrick Alfryn, Pastor, Pau, Reyes-Pérez, Paula, Saffie Awad, Paula, Chana, Pedro, Chan, Phillip, Kung, Pin-Jui, Chan, Piu, Pal, Pramod, Lingappa Kukkle, Prashanth, Ojha, Rajeev, Kaiyrzhanov, Rauan, Krüger, Rejko, Amouri, Rim, Weil, Rimona, Rajan, Roopa, Alcalay, Roy, Wu, Ruey-Meei, Borgohain, Rupam, Sassi, Samia Ben, Khachatryan, Samson, Bandres-Ciga, Sara, El-Sadig, Sarah, Wu, Serena, Groppa, Sergio, Azmin, Shahrul, Lim, Shen-Yang, Ur-Rehman, Shoaib, Ertan, Sibel, Stott, Simon, Jasaitye, Simona, Chowdhury, Sohini, Dumanis, Sonya, Bardien, Soraya, Lubbe, Steven, Koks, Sulev, Dey, Sumit, Foroud, Tatiana, Fon, Ted, Beach, Thomas, Gasser, Thomas, Anderson, Tim, Nguyen, Toan, Schirinzi, Tommaso, Shiraishi, Tomotaka, Pitcher, Toni, Tumas, Vitor, Mohamed, Wael, Kamel, Walaa A., Luo, Wei, Zhou, Xiaopu, Zewde, Yared Z., Song, Yeajin, Wen, Yi, Wu, Yihru, Joong Kim, Yun, Tavadyan, Zaruhi, Fang, Zih-Hua, Ojo, Oluwadamilola Omolara, Crea, Peter Wild, Abiodun, Oladunni Victoria, Levine, Kristin S, Abubakar, Sani Atta, Achoru, Charles Obiora, Adeniji, Olaleye Akinmola, Agabi, Osigwe Paul, Koretsky, Mathew J, Hall, Deborah A, Akinyemi, Rufus Olusola, Ali, Mohammed Wulgo, Shamim, Ejaz A, Padmanaban, Mahesh, Arigbodi, Ohwotemu Michael, Standaert, David G, Bello, Abiodun Hamzat, Dean, Marissa N, Erameh, Cyril Oshomah, Farombi, Temitope Hannah, Fawale, Michael Bimbola, Billingsley, Kimberley J, Imarhiagbe, Frank Aiwansoba, Jerez, Pilar Alvarez, Iwuozo, Emmanuel Uzodinma, Baker, Breeana, Komolafe, Morenikeji Adeyoyin, Malik, Laksh, Nwani, Paul Osemeke, Daida, Kensuke, Nwazor, Ernest Okwundu, Miano-Burkhardt, Abigail, Nyandaiti, Yakub Wilberforce, Obiabo, Yahaya Olugbo, Kluss, Jillian H, Odeniyi, Olanike Adedoyin, Hernandez, Dena G, Odiase, Francis Ehidiamen, Tayebi, Nahid, Ojini, Francis Ibe, Sidranksy, Ellen, Onwuegbuzie, Gerald Awele, D'Souza, Andrea M, Osaigbovo, Godwin Osawaru, Berhe, Bahafta, Reed, Xylena, Oshinaike, Olajumoke Olufemi, Leonard, Hampton L, Otubogun, Folajimi Morenikeji, Alvarado, Chelsea X, Oyakhire, Shyngle Imiewan, Ozomma, Simon Izuchukwu, Samuel, Sarah Chabiri, Taiwo, Funmilola Tolulope, Wahab, Kolawole Wasiu, Zubair, Yusuf Agboola, Kim, Jonggeol Jeffrey, Nalls, Mike A, Heilbron, Karl, Norcliffe-Kaufmann, Lucy, and Okubadejo, Njideka Ulunma

Published
2023
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29. Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Author

Katzdobler, Sabrina, Nitschmann, Alexander, Barthel, Henryk, Bischof, Gerard, Beyer, Leonie, Marek, Ken, Song, Mengmeng, Wagemann, Olivia, Palleis, Carla, Weidinger, Endy, Nack, Anne, Fietzek, Urban, Kurz, Carolin, Häckert, Jan, Stapf, Theresa, Ferschmann, Christian, Scheifele, Maximilian, Eckenweber, Florian, Biechele, Gloria, Franzmeier, Nicolai, Dewenter, Anna, Schönecker, Sonja, Saur, Dorothee, Schroeter, Matthias L., Rumpf, Jost-Julian, Rullmann, Michael, Schildan, Andreas, Patt, Marianne, Stephens, Andrew W., van Eimeren, Thilo, Neumaier, Bernd, Drzezga, Alexander, Danek, Adrian, Classen, Joseph, Bürger, Katharina, Janowitz, Daniel, Rauchmann, Boris-Stephan, Stöcklein, Sophia, Perneczky, Robert, Schöberl, Florian, Zwergal, Andreas, Höglinger, Günter U., Bartenstein, Peter, Villemagne, Victor, Seibyl, John, Sabri, Osama, Levin, Johannes, and Brendel, Matthias

Published
2023
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30. The Progressive Supranuclear Palsy Clinical Deficits Scale

Author

Piot, Ines, Schweyer, Kerstin, Respondek, Gesine, Stamelou, Maria, Sckopke, Philipp, Schenk, Thomas, Goetz, Christopher G, Stebbins, Glenn T, Höglinger, Günter U, Gasser, Thomas, Hermann, Andreas, Höglinger, Günter, Höllerhage, Matthias, Kimmich, Okka, Klockgether, Thomas, Levin, Johannes, Machetanz, Gerrit, Osterrath, Antje, Palleis, Carla, Prudlo, Johannes, Spottke, Annika, Berg, Daniela, Bürk, Katrin, Claßen, Joseph, Eggers, Carsten, Greuel, Andrea, Grimm, Max‐Joseph, Hermann, Lennard, Iankova, Vassilena, Jahn, Klaus, Jost, Wolfgang, Klietz, Martin, Kühn, Andrea, Marxreiter, Franz, Paschen, Steffen, Poetter‐Nerger, Monika, Preisl, Marie‐Therese, Prilop, Lisa, Tönges, Lars, Trenkwalder, Claudia, Warnecke, Tobias, Wegner, Florian, Winkler, Jürgen, Antonini, Angelo, P, Kailash P, L, Adam L, Colosimo, Carlo, Compta, Yaroslau, Corvol, Jean‐Christophe, I, Lawrence I, E, Anthony E, Litvan, Irene, R, Huw R, Nilsson, Christer, and Pantelyat, Alexander

Subjects
Pediatric, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Neurosciences, Brain Disorders, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Disease Progression, Female, Fingers, Humans, Male, Motor Skills, Reproducibility of Results, Supranuclear Palsy, Progressive, progressive supranuclear palsy, clinical rating scales, outcome measures, power calculation, DescribePSP study group, ProPSP study group, MDS-endorsed PSP study group, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundThere is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes.ObjectiveTo develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes.MethodsThe Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts).ResultsCognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P

Published
2020

31. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial

Author

Höglinger, Günter U, Litvan, Irene, Mendonca, Nuno, Wang, Deli, Zheng, Hui, Rendenbach-Mueller, Beatrice, Lon, Hoi-Kei, Jin, Ziyi, Fisseha, Nahome, Budur, Kumar, Gold, Michael, Ryman, Davis, Florian, Hana, Investigators, Arise, Ahmed, Anwar, Aiba, Ikuko, Albanese, Alberto, Bertram, Kelly, Bordelon, Yvette, Bower, James, Brosch, Jared, Claassen, Daniel, Colosimo, Carlo, Corvol, Jean-Christophe, Cudia, Paola, Daniele, Antonio, Defebvre, Luc, Driver-Dunckley, Erika, Duquette, Antoine, Eleopra, Roberto, Eusebio, Alexandre, Fung, Victor, Geldmacher, David, Golbe, Lawrence, Grandas, Francisco, Hall, Deborah, Hatano, Taku, Honig, Lawrence, Hui, Jennifer, Kerwin, Diana, Kikuchi, Akio, Kimber, Thomas, Kimura, Takashi, Kumar, Rajeev, Ljubenkov, Peter, Lorenzl, Stefan, Ludolph, Albert, Mari, Zoltan, McFarland, Nikolaus, Meissner, Wassilios, Rivera, Pablo Mir, Mochizuki, Hidek, Morgan, John, Munhoz, Renato, Nishikawa, Noriko, O`Sullivan, John, Oeda, Tomoko, Oizumi, Hideki, Onodera, Osamu, Ory-Magne, Fabienne, Peckham, Elizabeth, Postuma, Ronald, Quattrone, Aldo, Quinn, Joseph, Ruggieri, Stefano, Sarna, Justyna, Schulz, Paul E, Slevin, John, Tagliati, Michele, Wile, Daryl, Wszolek, Zbigniew, Xie, Tao, and Zesiewicz, Theresa

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Patient Safety, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Neurological, Administration, Intravenous, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Female, Humans, Male, Middle Aged, Supranuclear Palsy, Progressive, Treatment Outcome, tau Proteins, Arise Investigators, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundProgressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy.MethodsWe did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879.FindingsBetween Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI -2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [-1·6 to 3·6], -0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related.InterpretationA similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy.FundingAbbVie Inc.

Published
2021

34. Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases

Author

Graessner, Holm, Reinhard, Carola, Bäumer, Tobias, Baumgärtner, Annette, Brockmann, Knut, Brüggemann, Norbert, Bültmann, Eva, Erdmann, Jeanette, Heise, Kirstin, Höglinger, Günter, Hüning, Irina, Kaiser, Frank J., Klein, Christine, Klopstock, Thomas, Krägeloh-Mann, Ingeborg, Kraemer, Markus, Luedtke, Kerstin, Mücke, Martin, Musacchio, Thomas, Nadke, Andreas, Osmanovic, Alma, Ritter, Gabriele, Röse, Katharina, Schippers, Christopher, Schöls, Ludger, Schüle, Rebecca, Schulz, Jörg B., Sproß, Joachim, Stasch, Eveline, Wunderlich, Gilbert, and Münchau, Alexander

Published
2024
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35. Associations between sex, body mass index and the individual microglial response in Alzheimer’s disease

Author

Biechele, Gloria, Rauchmann, Boris-Stephan, Janowitz, Daniel, Buerger, Katharina, Franzmeier, Nicolai, Weidinger, Endy, Guersel, Selim, Schuster, Sebastian, Finze, Anika, Harris, Stefanie, Lindner, Simon, Albert, Nathalie L., Wetzel, Christian, Rupprecht, Rainer, Rominger, Axel, Palleis, Carla, Katzdobler, Sabrina, Burow, Lena, Kurz, Carolin, Zaganjori, Mirlind, Trappmann, Lena-Katharina, Goldhardt, Oliver, Grimmer, Timo, Haeckert, Jan, Keeser, Daniel, Stoecklein, Sophia, Morenas-Rodriguez, Estrella, Bartenstein, Peter, Levin, Johannes, Höglinger, Günter U., Simons, Mikael, Perneczky, Robert, and Brendel, Matthias

Published
2024
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36. Distinct molecular profiles of skull bone marrow in health and neurological disorders

Author

Kolabas, Zeynep Ilgin, Kuemmerle, Louis B., Perneczky, Robert, Förstera, Benjamin, Ulukaya, Selin, Ali, Mayar, Kapoor, Saketh, Bartos, Laura M., Büttner, Maren, Caliskan, Ozum Sehnaz, Rong, Zhouyi, Mai, Hongcheng, Höher, Luciano, Jeridi, Denise, Molbay, Muge, Khalin, Igor, Deligiannis, Ioannis K., Negwer, Moritz, Roberts, Kenny, Simats, Alba, Carofiglio, Olga, Todorov, Mihail I., Horvath, Izabela, Ozturk, Furkan, Hummel, Selina, Biechele, Gloria, Zatcepin, Artem, Unterrainer, Marcus, Gnörich, Johannes, Roodselaar, Jay, Shrouder, Joshua, Khosravani, Pardis, Tast, Benjamin, Richter, Lisa, Díaz-Marugán, Laura, Kaltenecker, Doris, Lux, Laurin, Chen, Ying, Zhao, Shan, Rauchmann, Boris-Stephan, Sterr, Michael, Kunze, Ines, Stanic, Karen, Kan, Vanessa W.Y., Besson-Girard, Simon, Katzdobler, Sabrina, Palleis, Carla, Schädler, Julia, Paetzold, Johannes C., Liebscher, Sabine, Hauser, Anja E., Gokce, Ozgun, Lickert, Heiko, Steinke, Hanno, Benakis, Corinne, Braun, Christian, Martinez-Jimenez, Celia P., Buerger, Katharina, Albert, Nathalie L., Höglinger, Günter, Levin, Johannes, Haass, Christian, Kopczak, Anna, Dichgans, Martin, Havla, Joachim, Kümpfel, Tania, Kerschensteiner, Martin, Schifferer, Martina, Simons, Mikael, Liesz, Arthur, Krahmer, Natalie, Bayraktar, Omer A., Franzmeier, Nicolai, Plesnila, Nikolaus, Erener, Suheda, Puelles, Victor G., Delbridge, Claire, Bhatia, Harsharan Singh, Hellal, Farida, Elsner, Markus, Bechmann, Ingo, Ondruschka, Benjamin, Brendel, Matthias, Theis, Fabian J., and Erturk, Ali

Published
2023
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40. Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database

Author

Viscidi, Emma, Litvan, Irene, Dam, Tien, Juneja, Maneesh, Li, Li, Krzywy, Henry, Eaton, Susan, Hall, Susan, Kupferman, Joseph, and Höglinger, Günter U

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Pediatric, Clinical Research, Neurological, movement disorder, natural history, neurodegenerative disease, progressive supranuclear palsy, rare disease, Psychology, Clinical sciences, Biological psychology
Abstract

Background: Progressive supranuclear palsy is a rare neurodegenerative movement disorder and little is known about its epidemiology. Objective: Estimate age-adjusted prevalence of progressive supranuclear palsy and describe antecedent diagnoses and progressive supranuclear palsy patient features in the 5 years before first diagnostic code. Methods: In a nested case-control study in the IBM MarketScan Commercial and Medicare Supplemental Databases, a large set of US insurance databases containing medical service and prescription drug claims from employer-based commercial and Medicare supplemental health insurance plans, progressive supranuclear palsy cases (identified via International Statistical Classification of Diseases 9th/10th revision codes) and controls were included if enrollment was ≥1 month in the study period (October 1, 2015-October 31, 2017). Two controls with no diagnosis codes for PSP were matched to cases on birth year, sex, enrollment time in the database, and pharmacy benefit eligibility. Controls were assigned a randomly selected index date from their eligibility period. Prevalence of progressive supranuclear palsy was estimated in 2016 among patients with ≥1 month of continuous enrollment in that year. Prevalence ratios for comorbidities (claim/diagnosis codes) were examined in the ≤ 5 years before index date (first progressive supranuclear palsy claim date). Results: Age-adjusted progressive supranuclear palsy prevalence was 2.95/100,000 in 2016. The most common diagnosis codes in cases vs. controls in the 5 years pre-index were gait abnormalities (79.3 vs. 21.8%), pain in joint (54.9 vs. 36.0%), Parkinson's disease (54.6 vs. 1.0%), fatigue (49.8 vs. 21.6%), and cerebrovascular disease (45.6 vs. 16.4%). Conclusions: In this large database analysis, based on preliminary analyses, the prevalence of diagnosed progressive supranuclear palsy was 2.95/100,000, which is lower than many prior studies. Typical symptoms suggestive of progressive supranuclear palsy were present before index date, indicating a potential delay in time to diagnosis. The identification of diagnostic codes for clinical features of progressive supranuclear palsy that occurred before index date may be used to develop predictive models to identify potential progressive supranuclear palsy patients earlier in their disease course.

Published
2021

41. Distribution patterns of tau pathology in progressive supranuclear palsy

Author

Kovacs, Gabor G, Lukic, Milica Jecmenica, Irwin, David J, Arzberger, Thomas, Respondek, Gesine, Lee, Edward B, Coughlin, David, Giese, Armin, Grossman, Murray, Kurz, Carolin, McMillan, Corey T, Gelpi, Ellen, Compta, Yaroslau, van Swieten, John C, Laat, Laura Donker, Troakes, Claire, Al-Sarraj, Safa, Robinson, John L, Roeber, Sigrun, Xie, Sharon X, Lee, Virginia M-Y, Trojanowski, John Q, and Höglinger, Günter U

Subjects
Biomedical and Clinical Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Rare Diseases, Acquired Cognitive Impairment, Aging, Alzheimer's Disease, Frontotemporal Dementia (FTD), Dementia, Neurodegenerative, Brain Disorders, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Aged, Brain, Cohort Studies, Female, Humans, Male, Middle Aged, Supranuclear Palsy, Progressive, tau Proteins, Coiled body, Neurofibrillary tangle, Progressive supranuclear palsy, Propagation, Richardson syndrome, Sequential involvement, Stage, Tau, Tauopathy, Tufted astrocyte, Clinical Sciences, Neurology & Neurosurgery
Abstract

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. We used conditional probability and logistic regression to model the sequential distribution of tau pathologies across different brain regions. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis in different clinical subtypes. However, clinical subtypes are distinguished not only by total tau load but rather cell-type (neuronal versus glial) specific vulnerability patterns of brain regions suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies. For Richardson syndrome (n = 81) we recognize six sequential steps of involvement of brain regions by the combination of cellular tau pathologies. This is translated to six stages for the practical neuropathological diagnosis by the evaluation of the subthalamic nucleus, globus pallidus, striatum, cerebellum with dentate nucleus, and frontal and occipital cortices. This system can be applied to further clinical subtypes by emphasizing whether they show caudal (cerebellum/dentate nucleus) or rostral (cortical) predominant, or both types of pattern. Defining cell-specific stages of tau pathology helps to identify preclinical or early-stage cases for the better understanding of early pathogenic events, has implications for understanding the clinical subtype-specific dynamics of disease-propagation, and informs tau-neuroimaging on distribution patterns.

Published
2020

43. Validation of the movement disorder society criteria for the diagnosis of 4-repeat tauopathies.

Author

Respondek, Gesine, Grimm, Max-Joseph, Piot, Ines, Arzberger, Thomas, Compta, Yaroslau, Englund, Elisabet, Ferguson, Leslie, Gelpi, Ellen, Roeber, Sigrun, Giese, Armin, Grossman, Murray, Irwin, David, Meissner, Wassilios, Nilsson, Christer, Pantelyat, Alexander, Rajput, Alex, van Swieten, John, Troakes, Claire, and Höglinger, Günter

Subjects
Four-repeat tauopathies, corticobasal degeneration, diagnostic criteria, progressive supranuclear palsy, Aged, Brain, Female, Humans, Male, Middle Aged, Multiple System Atrophy, Parkinson Disease, Parkinsonian Disorders, Supranuclear Palsy, Progressive, Tauopathies
Abstract

BACKGROUND: The Movement Disorder Society criteria for progressive supranuclear palsy introduced the category probable 4-repeat (4R)-tauopathy for joint clinical diagnosis of progressive supranuclear palsy and corticobasal degeneration. OBJECTIVES: To validate the accuracy of these clinical criteria for probable 4R-tauopathy to predict underlying 4R-tauopathy pathology. METHODS: Diagnostic accuracy for 4R-tauopathies according to the established criteria was estimated retrospectively in autopsy-confirmed patients with progressive supranuclear palsy and corticobasal degeneration (grouped as 4R-tauopathies), and Parkinsons disease, multiple system atrophy, and frontotemporal lobar degeneration (grouped as non-4R-tauopathies). RESULTS: We identified 250 cases with progressive supranuclear palsy (N = 195) and corticobasal degeneration (N = 55) and with and non-4R-tauopathies (N = 161). Sensitivity and specificity of probable 4R-tauopathy was 10% and 99% in the first year and 59% and 88% at final record. CONCLUSIONS: The new diagnostic category probable 4R-tauopathy showed high specificity and may be suitable for the recruitment of patients with progressive supranuclear palsy and corticobasal degeneration into therapeutic trials targeting 4R-tauopathy. The low sensitivity underpins the need for diagnostic biomarkers. © 2019 International Parkinson and Movement Disorder Society.

Published
2020

44. Morbus Parkinson

Author

Seifert, Roland, Höglinger, Günter, Ludwig, Wolf-Dieter, editor, Mühlbauer, Bernd, editor, and Seifert, Roland, editor

Published
2022
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45. Towards a consensus on developmental regression.

Author

Zhang, Dajie, Bedogni, Francesco, Boterberg, Sofie, Camfield, Carol, Camfield, Peter, Charman, Tony, Curfs, Leopold, Einspieler, Christa, Esposito, Gianluca, De Filippis, Bianca, Goin-Kochel, Robin P, Höglinger, Günter U, Holzinger, Daniel, Iosif, Ana-Maria, Lancioni, Giulio E, Landsberger, Nicoletta, Laviola, Giovanni, Marco, Eva M, Müller, Michael, Neul, Jeffrey L, Nielsen-Saines, Karin, Nordahl-Hansen, Anders, O'Reilly, Mark F, Ozonoff, Sally, Poustka, Luise, Roeyers, Herbert, Rankovic, Marija, Sigafoos, Jeff, Tammimies, Kristiina, Townend, Gillian S, Zwaigenbaum, Lonnie, Zweckstetter, Markus, Bölte, Sven, and Marschik, Peter B

Subjects
Humans, Consensus, Regression, Psychology, Medical and Health Sciences, Psychology and Cognitive Sciences, Behavioral Science & Comparative Psychology
Published
2019

46. How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy.

Author

Grimm, Max-Joseph, Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Ferguson, Leslie, Gelpi, Ellen, Giese, Armin, Grossman, Murray, Irwin, David J, Pantelyat, Alexander, Rajput, Alex, Roeber, Sigrun, van Swieten, John C, Troakes, Claire, Antonini, Angelo, Bhatia, Kailash P, Colosimo, Carlo, van Eimeren, Thilo, Kassubek, Jan, Levin, Johannes, Meissner, Wassilios G, Nilsson, Christer, Oertel, Wolfgang H, Piot, Ines, Poewe, Werner, Wenning, Gregor K, Boxer, Adam, Golbe, Lawrence I, Josephs, Keith A, Litvan, Irene, Morris, Huw R, Whitwell, Jennifer L, Compta, Yaroslau, Corvol, Jean-Christophe, Lang, Anthony E, Rowe, James B, Höglinger, Günter U, and Movement Disorder Society-endorsed PSP Study Group

Subjects
Movement Disorder Society-endorsed PSP Study Group, Brain, Humans, Parkinsonian Disorders, Supranuclear Palsy, Progressive, Ocular Motility Disorders, Sensation Disorders, Autopsy, Retrospective Studies, Cohort Studies, Adult, Aged, Aged, 80 and over, Middle Aged, Societies, Medical, Female, Male, Postural Balance, Cognitive Dysfunction, autopsy, diversity, phenotype, progressive supranuclear palsy, Brain Disorders, Pediatric, Neurosciences, Rare Diseases, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, 4.2 Evaluation of markers and technologies, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences
Abstract

BackgroundThe Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them.MethodsWe retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations.ResultsComprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1.ConclusionsThe proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society.

Published
2019

47. Symptomatology in 4-repeat tauopathies is associated with data-driven topology of [18F]-PI-2620 tau-PET signal

Author

Schönecker, Sonja, Palleis, Carla, Franzmeier, Nicolai, Katzdobler, Sabrina, Ferschmann, Christian, Schuster, Sebastian, Finze, Anika, Scheifele, Maximilian, Prix, Catharina, Fietzek, Urban, Weidinger, Endy, Nübling, Georg, Vöglein, Jonathan, Patt, Marianne, Barthel, Henryk, Sabri, Osama, Danek, Adrian, Höglinger, Günter U., Brendel, Matthias, and Levin, Johannes

Published
2023
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