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1. Differential Psychological Treatment Effects in Patients With Late-Life Depression and a History of Childhood Maltreatment

Author

Müller, Julia, Elsaesser, Moritz, Müller, Wiebke, Hellmich, Martin, Hammen, Magdalena, Zehender, Nadine, Riedel-Heller, Steffi, Bewernick, Bettina H., Wagner, Michael, Frölich, Lutz, Peters, Oliver, Dafsari, Forugh S., Domschke, Katharina, Jessen, Frank, Hautzinger, Martin, and Schramm, Elisabeth

Abstract

•What is the primary question addressed by this study?Does childhood maltreatment affect the psychological treatment outcomes in late-life depression?•What is the main finding of this study?In older individuals with depression and childhood maltreatment, both specific and non-specific psychotherapy equally reduce depressive symptoms. However, in patients withoutchildhood maltreatment, cognitive behavioral therapy for late-life-depression demonstrates greater efficacy over non-specific supportive psychotherapy.•What is the meaning of the finding?Practioners should consider a history of early trauma in their choice between specific and non-specific interventions.

Published
2024
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2. BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study

Author

Cognat, Emmanuel, Sabia, Séverine, Fayel, Alexandra, Lilamand, Matthieu, Handels, Ron, Fascendini, Sara, Bergh, Sverre, Frisoni, Giovanni B., Fabbo, Andrea, Tsolaki, Magdalina, Frölich, Lutz, Peters, Oliver, Merlo, Paola, Ciccone, Alfonso, Mecocci, Patrizia, Dumurgier, Julien, Defanti, Carlo A., Hugon, Jacques, and Paquet, Claire

Abstract

•What is the primary question addressed by this study?Do patients with severe behavioral and psychological symptoms of dementia show specific neuropsychiatric patterns on symptoms depending on etiology?•What is the main finding of this study?Patients with Lewy body dementia / Parkinson's disease dementia (LBD/PD) displayed more hallucinations, more delusion and more anxiety than patients with cognitive impairment of other origin while patients with frontotemporal dementia showed more disinhibition and less delusion.•What is the meaning of the finding?Different profiles were identified depending on etiology in patients with severe behavioral and psychological symptoms of dementia suggesting that precise characterization might be performed regardless of the severity of neuropsychiatric symptoms to adapt management.

Published
2023
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3. Rare variants in IFFO1, DTNB, NLRC3and SLC22A10associate with Alzheimer’s disease CSF profile of neuronal injury and inflammation

Author

Neumann, Alexander, Küçükali, Fahri, Bos, Isabelle, Vos, Stephanie J. B., Engelborghs, Sebastiaan, De Pooter, Tim, Joris, Geert, De Rijk, Peter, De Roeck, Ellen, Tsolaki, Magda, Verhey, Frans, Martinez-Lage, Pablo, Tainta, Mikel, Frisoni, Giovanni, Blin, Oliver, Richardson, Jill, Bordet, Régis, Scheltens, Philip, Popp, Julius, Peyratout, Gwendoline, Johannsen, Peter, Frölich, Lutz, Vandenberghe, Rik, Freund-Levi, Yvonne, Streffer, Johannes, Lovestone, Simon, Legido-Quigley, Cristina, ten Kate, Mara, Barkhof, Frederik, Strazisar, Mojca, Zetterberg, Henrik, Bertram, Lars, Visser, Pieter Jelle, van Broeckhoven, Christine, and Sleegers, Kristel

Abstract

Alzheimer’s disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3,and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3,and SLC22A10heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2and CASZ1were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.

Published
2022
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4. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W., Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C., Damotte, Vincent, Naj, Adam C., Boland, Anne, Vronskaya, Maria, van der Lee, Sven J., Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R., Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L., Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B., Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N., Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W., Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L., Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V., Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C., Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T., Adams, Hieab H., Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A., Dombroski, Beth A., Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B., Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S., Meslage, Stéphane, Kornhuber, Johannes, White, Charles C., Song, Yuenjoo, Barber, Robert C., Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M., Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L. Adrienne, Albert, Marilyn S., De Deyn, Peter P., Gu, Wei, Himali, Jayanadra J., Beekly, Duane, Squassina, Alessio, Hartmann, Annette M., Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E., Doody, Rachelle S., Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J., Benito, Yolanda A., Holmes, Clive, Karamujić-Čomić, Hata, Frosch, Matthew P., Thonberg, Hakan, Maier, Wolfgang, Roshchupkin, Gennady, Ghetti, Bernardino, Giedraitis, Vilmantas, Kawalia, Amit, Li, Shuo, Huebinger, Ryan M., Kilander, Lena, Moebus, Susanne, Hernández, Isabel, Kamboh, M. Ilyas, Brundin, RoseMarie, Turton, James, Yang, Qiong, Katz, Mindy J., Concari, Letizia, Lord, Jenny, Beiser, Alexa S., Keene, C. Dirk, Helisalmi, Seppo, Kloszewska, Iwona, Kukull, Walter A., Koivisto, Anne Maria, Lynch, Aoibhinn, Tarraga, Lluís, Larson, Eric B., Haapasalo, Annakaisa, Lawlor, Brian, Mosley, Thomas H., Lipton, Richard B., Solfrizzi, Vincenzo, Gill, Michael, Longstreth, W. T., Montine, Thomas J., Frisardi, Vincenza, Diez-Fairen, Monica, Rivadeneira, Fernando, Petersen, Ronald C., Deramecourt, Vincent, Alvarez, Ignacio, Salani, Francesca, Ciaramella, Antonio, Boerwinkle, Eric, Reiman, Eric M., Fievet, Nathalie, Rotter, Jerome I., Reisch, Joan S., Hanon, Olivier, Cupidi, Chiara, Andre Uitterlinden, A. G., Royall, Donald R., Dufouil, Carole, Maletta, Raffaele Giovanni, de Rojas, Itziar, Sano, Mary, Brice, Alexis, Cecchetti, Roberta, George-Hyslop, Peter St, Ritchie, Karen, Tsolaki, Magda, Tsuang, Debby W., Dubois, Bruno, Craig, David, Wu, Chuang-Kuo, Soininen, Hilkka, Avramidou, Despoina, Albin, Roger L., Fratiglioni, Laura, Germanou, Antonia, Apostolova, Liana G., Keller, Lina, Koutroumani, Maria, Arnold, Steven E., Panza, Francesco, Gkatzima, Olymbia, Asthana, Sanjay, Hannequin, Didier, Whitehead, Patrice, Atwood, Craig S., Caffarra, Paolo, Hampel, Harald, Quintela, Inés, Carracedo, Ángel, Lannfelt, Lars, Rubinsztein, David C., Barnes, Lisa L., Pasquier, Florence, Frölich, Lutz, Barral, Sandra, McGuinness, Bernadette, Beach, Thomas G., Johnston, Janet A., Becker, James T., Passmore, Peter, Bigio, Eileen H., Schott, Jonathan M., Bird, Thomas D., Warren, Jason D., Boeve, Bradley F., Lupton, Michelle K., Bowen, James D., Proitsi, Petra, Boxer, Adam, Powell, John F., Burke, James R., Kauwe, John S. K., Burns, Jeffrey M., Mancuso, Michelangelo, Buxbaum, Joseph D., Bonuccelli, Ubaldo, Cairns, Nigel J., McQuillin, Andrew, Cao, Chuanhai, Livingston, Gill, Carlson, Chris S., Bass, Nicholas J., Carlsson, Cynthia M., Hardy, John, Carney, Regina M., Bras, Jose, Carrasquillo, Minerva M., Guerreiro, Rita, Allen, Mariet, Chui, Helena C., Fisher, Elizabeth, Masullo, Carlo, Crocco, Elizabeth A., DeCarli, Charles, Bisceglio, Gina, Dick, Malcolm, Ma, Li, Duara, Ranjan, Graff-Radford, Neill R., Evans, Denis A., Hodges, Angela, Faber, Kelley M., Scherer, Martin, Fallon, Kenneth B., Riemenschneider, Matthias, Fardo, David W., Heun, Reinhard, Farlow, Martin R., Kölsch, Heike, Ferris, Steven, Leber, Markus, Foroud, Tatiana M., Heuser, Isabella, Galasko, Douglas R., Giegling, Ina, Gearing, Marla, Hüll, Michael, Geschwind, Daniel H., Gilbert, John R., Morris, John, Green, Robert C., Mayo, Kevin, Growdon, John H., Feulner, Thomas, Hamilton, Ronald L., Harrell, Lindy E., Drichel, Dmitriy, Honig, Lawrence S., Cushion, Thomas D., Huentelman, Matthew J., Hollingworth, Paul, Hulette, Christine M., Hyman, Bradley T., Marshall, Rachel, Jarvik, Gail P., Meggy, Alun, Abner, Erin, Menzies, Georgina E., Jin, Lee-Way, Leonenko, Ganna, Real, Luis M., Jun, Gyungah R., Baldwin, Clinton T., Grozeva, Detelina, Karydas, Anna, Russo, Giancarlo, Kaye, Jeffrey A., Kim, Ronald, Jessen, Frank, Kowall, Neil W., Vellas, Bruno, Kramer, Joel H., Vardy, Emma, LaFerla, Frank M., Jöckel, Karl-Heinz, Lah, James J., Dichgans, Martin, Leverenz, James B., Mann, David, Levey, Allan I., Pickering-Brown, Stuart, Lieberman, Andrew P., Klopp, Norman, Lunetta, Kathryn L., Wichmann, H-Erich, Lyketsos, Constantine G., Morgan, Kevin, Marson, Daniel C., Brown, Kristelle, Martiniuk, Frank, Medway, Christopher, Mash, Deborah C., Nöthen, Markus M., Masliah, Eliezer, Hooper, Nigel M., McCormick, Wayne C., Daniele, Antonio, McCurry, Susan M., Bayer, Anthony, McDavid, Andrew N., Gallacher, John, McKee, Ann C., van den Bussche, Hendrik, Mesulam, Marsel, Brayne, Carol, Miller, Bruce L., Riedel-Heller, Steffi, Miller, Carol A., Miller, Joshua W., Al-Chalabi, Ammar, Morris, John C., Shaw, Christopher E., Myers, Amanda J., Wiltfang, Jens, O’Bryant, Sid, Olichney, John M., Alvarez, Victoria, Parisi, Joseph E., Singleton, Andrew B., Paulson, Henry L., Collinge, John, Perry, William R., Mead, Simon, Peskind, Elaine, Cribbs, David H., Rossor, Martin, Pierce, Aimee, Ryan, Natalie S., Poon, Wayne W., Nacmias, Benedetta, Potter, Huntington, Sorbi, Sandro, Quinn, Joseph F., Sacchinelli, Eleonora, Raj, Ashok, Spalletta, Gianfranco, Raskind, Murray, Caltagirone, Carlo, Bossù, Paola, Orfei, Maria Donata, Reisberg, Barry, Clarke, Robert, Reitz, Christiane, Smith, A David, Ringman, John M., Warden, Donald, Roberson, Erik D., Wilcock, Gordon, Rogaeva, Ekaterina, Bruni, Amalia Cecilia, Rosen, Howard J., Gallo, Maura, Rosenberg, Roger N., Ben-Shlomo, Yoav, Sager, Mark A., Mecocci, Patrizia, Saykin, Andrew J., Pastor, Pau, Cuccaro, Michael L., Vance, Jeffery M., Schneider, Julie A., Schneider, Lori S., Slifer, Susan, Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tang, Mitchell, Tanzi, Rudolph E., Trojanowski, John Q., Troncoso, Juan C., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Wilhelmsen, Kirk C., Williamson, Jennifer, Wingo, Thomas S., Woltjer, Randall L., Wright, Clinton B., Yu, Chang-En, Yu, Lei, Saba, Yasaman, Pilotto, Alberto, Bullido, Maria J., Peters, Oliver, Crane, Paul K., Bennett, David, Bosco, Paola, Coto, Eliecer, Boccardi, Virginia, De Jager, Phil L., Lleo, Alberto, Warner, Nick, Lopez, Oscar L., Ingelsson, Martin, Deloukas, Panagiotis, Cruchaga, Carlos, Graff, Caroline, Gwilliam, Rhian, Fornage, Myriam, Goate, Alison M., Sanchez-Juan, Pascual, Kehoe, Patrick G., Amin, Najaf, Ertekin-Taner, Nilifur, Berr, Claudine, Debette, Stéphanie, Love, Seth, Launer, Lenore J., Younkin, Steven G., Dartigues, Jean-Francois, Corcoran, Chris, Ikram, M. Arfan, Dickson, Dennis W., Nicolas, Gael, Campion, Dominique, Tschanz, JoAnn, Schmidt, Helena, Hakonarson, Hakon, Clarimon, Jordi, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay A., Van Broeckhoven, Christine, C. O’Donovan, Michael, DeStefano, Anita L., Jones, Lesley, Haines, Jonathan L., Deleuze, Jean-Francois, Owen, Michael J., Gudnason, Vilmundur, Mayeux, Richard, Escott-Price, Valentina, Psaty, Bruce M., Ramirez, Alfredo, Wang, Li-San, Ruiz, Agustin, van Duijn, Cornelia M., Holmans, Peter A., Seshadri, Sudha, Williams, Julie, Amouyel, Phillippe, Schellenberg, Gerard D., Lambert, Jean-Charles, and Pericak-Vance, Margaret A.

Abstract

Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1,and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P= 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019
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5. Enrichment factors for clinical trials in mild-to-moderate Alzheimer's disease

Author

Ballard, Clive, Atri, Alireza, Boneva, Neli, Cummings, Jeffrey L., Frölich, Lutz, Molinuevo, José Luis, Tariot, Pierre N., and Raket, Lars Lau

Abstract

Heterogeneity of outcomes in Alzheimer's disease (AD) clinical trials necessitates large sample sizes and contributes to study failures. This analysis determined whether mild-to-moderate AD populations could be enriched for cognitive decline based on apolipoprotein (APOE) ε4 genotype, family history of AD, and amyloid abnormalities.

Published
2019
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6. A metabolite-based machine learning approach to diagnose Alzheimer-type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

Author

Stamate, Daniel, Kim, Min, Proitsi, Petroula, Westwood, Sarah, Baird, Alison, Nevado-Holgado, Alejo, Hye, Abdul, Bos, Isabelle, Vos, Stephanie J.B., Vandenberghe, Rik, Teunissen, Charlotte E., Kate, Mara Ten, Scheltens, Philip, Gabel, Silvy, Meersmans, Karen, Blin, Olivier, Richardson, Jill, De Roeck, Ellen, Engelborghs, Sebastiaan, Sleegers, Kristel, Bordet, Régis, Ramit, Lorena, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Alcolea, Daniel, Lléo, Alberto, Peyratout, Gwendoline, Tainta, Mikel, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Dobricic, Valerija, Frisoni, Giovanni B., Molinuevo, José L., Wallin, Anders, Popp, Julius, Martinez-Lage, Pablo, Bertram, Lars, Blennow, Kaj, Zetterberg, Henrik, Streffer, Johannes, Visser, Pieter J., Lovestone, Simon, and Legido-Quigley, Cristina

Abstract

Machine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer Disease (AD). Here we set out to test the performance of metabolites in blood to categorize AD when compared to CSF biomarkers.

Published
2019
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7. Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer's disease

Author

Peters, Oliver, Fuentes, Manuel, Joachim, Lisa Katharina, Jessen, Frank, Luckhaus, Christian, Kornhuber, Johannes, Pantel, Johannes, Hüll, Michael, Schmidtke, Klaus, Rüther, Eckart, Möller, Hans-Jürgen, Kurz, Alexander, Wiltfang, Jens, Maier, Wolfgang, Wiese, Birgitt, Frölich, Lutz, and Heuser, Isabella

Abstract

Several studies have tested the N-methyl-D-aspartate–receptor antagonist memantine as an add-on to pre-existing treatment with acetylcholinesterase inhibitors. The objective of this study was to evaluate the efficacy and safety of a combined memantine and galantamine-CR de novo regimen compared with galantamine-CR only treatment in never treated patients with mild-to-moderate Alzheimer's disease (AD).

Published
2015
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8. Subjective cognitive decline is related to CSF biomarkers of AD in patients with MCI

Author

Wolfsgruber, Steffen, Jessen, Frank, Koppara, Alexander, Kleineidam, Luca, Schmidtke, Klaus, Frölich, Lutz, Kurz, Alexander, Schulz, Stefanie, Hampel, Harald, Heuser, Isabella, Peters, Oliver, Reischies, Friedel M., Jahn, Holger, Luckhaus, Christian, Hüll, Michael, Gertz, Hermann-Josef, Schröder, Johannes, Pantel, Johannes, Rienhoff, Otto, Rüther, Eckart, Henn, Fritz, Wiltfang, Jens, Maier, Wolfgang, Kornhuber, Johannes, and Wagner, Michael

Abstract

To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD).

Published
2015
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9. Entwicklung eines Fragebogens zur Identifikation der Präferenz von Patienten für ein konventionelles oder ein direktes orales Antikoagulanz

Author

Zolfaghari, Shabnam, Harenberg, Job, Wehling, Martin, Frölich, Lutz, and Weiss, Christel

Abstract

Hintergrund:Eine orale Antikoagulation kann heute mit Vitamin-K-abhängigen (VKA) oder neuen, nicht Vitamin-K-abhängigen oralen Antikoagulanzien (NOAK) durchgeführt werden. Es ist daher möglich, Patienten in den Entscheidungsprozess zur Wahl des Antikoagulanz einzubinden. Die Bedeutung der Präferenz für einen der beiden Typen von Antikoagulanzien hat Eingang in verschiedene internationale Leitlinien zur Embolieprophylaxe bei Patienten mit Vorhofflimmern gefunden. Methode:Beschrieben wird die Entwicklung eines kurzen Fragebogens, mit dessen Hilfe die Präferenz für einen der beiden Typen von oralen Antikoagulanzien bei Patienten, die unter Behandlung mit VKA stehen, identifiziert werden kann. Ergebnisse:Mit dem Einsatz der Fragebögen Freiburger Persönlichkeitsinventar (FPI-R), Selbstbeurteilungsbogen (SF-12), Angstinventar (STAI) und eines eigenen Fragebogens zur Antikoagulation wurden mittels logistischer Regressionsanalyse sieben Items identifiziert, anhand derer mit einer Wahrscheinlichkeit von etwa 90% die Bereitschaft von Patienten festgestellt werden kann, von einem VKA auf ein NOAK zu wechseln. Schlussfolgerung:In weiteren Untersuchungen bleibt zu klären, inwieweit mit diesem Fragebogen auch diejenigen Patienten identifiziert werden können, die eine Behandlung mit VKA bevorzugen. Background:Oral anticoagulant therapy is currently performed using vitamin K-dependent (VKA) or novel, non-vitamin-K-dependent (NOAC) anticoagulants. Patients can thus be involved into the decision process which type of anticoagulants to use. Preference of patients for a specific type of anticoagulants is included in several international guidelines for prophylaxis of embolic events in patients with atrial fibrillation. Method:Description of the development of a short questionnaire to identify this preference in patients treated with VKA. Results:Using the questionnaires Freiburger personality inventory (FPI-R), health survey SF-12, State-Trait Anxiety Inventory (STAI) and a self-developed questionnaire on anticoagulant therapy, multiple regression analysis identified 7 items for the willingness of patients to change anticoagulation from VKA to NOAC with a probability of about 90%. Conclusion:Further investigations have to be performed to identify the preference of patients for anticoagulation with VKA using this short questionnaire.

Published
2014
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10. No consistent evidence for association between mtDNA variants and Alzheimer disease

Author

Hudson, G., Sims, R., Harold, D., Chapman, J., Hollingworth, P., Gerrish, A., Russo, G., Hamshere, M., Moskvina, V., Jones, N., Thomas, C., Stretton, A., Holmans, P.A., O'Donovan, M.C., Owen, M.J., Williams, J., Chinnery, P.F., Harold, Denise, Abraham, Richard, Hollingworth, Paul, Sims, Rebecca, Gerrish, Amy, Chapman, Jade, Russo, Giancarlo, Hamshere, Marian, Pahwa, Jaspreet Singh, Moskvina, Valentina, Dowzell, Kimberley, Williams, Amy, Jones, Nicola, Thomas, Charlene, Stretton, Alexandra, Morgan, Angharad, Lovestone, Simon, Powell, John, Proitsi, Petroula, Lupton, Michelle K, Brayne, Carol, Rubinsztein, David C., Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Morgan, Kevin, Brown, Kristelle, Passmore, Peter, Craig, David, McGuinness, Bernadette, Todd, Stephen, Johnston, Janet, Holmes, Clive, Mann, David, Smith, A. David, Love, Seth, Kehoe, Patrick G., Hardy, John, Mead, Simon, Fox, Nick, Rossor, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Heun, Reiner, Kölsch, Heike, Schürmann, Britta, van den Bussche, Hendrik, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Rujescu, Dan, Goate, Alison, Kauwe, John S.K., Cruchaga, Carlos, Nowotny, Petra, Morris, John C., Mayo, Kevin, Livingston, Gill, Bass, Nicholas J., Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Holmans, Peter, O'Donovan, Michael, Owen, Michael J., and Williams, Julie

Abstract

Although several studies have described an association between Alzheimer disease (AD) and genetic variation of mitochondrial DNA (mtDNA), each has implicated different mtDNA variants, so the role of mtDNA in the etiology of AD remains uncertain.

Published
2012
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12. Neuropsychologisch fundierte kognitive Verhaltenstherapie für Patienten mit Alzheimer-Krankheit im Frühstadium

Author

Kurz, Alexander, Cramer, Barbara, Egert, Silvia, Frölich, Lutz, Gertz, Hermann-Josef, Knorr, Carolin, Thöne-Otto, Angelika, Wagenpfeil, Stefan, and Werheid, Katja

Abstract

Die KORDIAL-Studie (Kognitiv-verhaltenstherapeutische ressourcenorientierte Therapie früher Demenzen im Alltag) ist eine multizentrische, randomisierte, kontrollierte, einfach-blinde Parallelgruppen-Studie zur Evaluation der Wirksamkeit einer neuropsychologisch fundierten verhaltenstherapeutischen Intervention für Patienten im klinischen Frühstadium der Alzheimer-Krankheit unter Alltagsbedingungen. Die experimentelle Intervention wurde speziell auf die Bedürfnisse und Fähigkeiten von Patienten mit beginnender Demenz abgestimmt. Sie zielt sowohl auf die Aufrechterhaltung der Funktionsfähigkeit im Alltag, vor allem durch Vermittlung von Strategien zur Kompensation kognitiver Defizite, als auch auf die emotionale Bewältigung der Krankheit und auf die Prävention sekundärer psychopathologischer Symptome ab. Um möglichst dauerhafte Veränderungen im Alltag zu erzielen, werden die Bezugspersonen der Patienten systematisch in die Intervention einbezogen. Im Falle des positiven Ausgangs der Studie könnte eine auf neuropsychologischen Erkenntnissen basierende Verhaltenstherapie zu einem etablierten Bestandteil der Behandlung von Patienten mit beginnender Demenz werden.

Published
2008
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15. Selbstberichtete kognitive Funktions- fähigkeit und Lebensqualität

Author

Bullinger, Monika, Petersen, Corinna, von den Driesch, Volker, Daniel, Dietmar, Irrgang, Valeska, Ernen, Carolin, and Frölich, Lutz

Abstract

Zusammenfassung:Im Rahmen einer Anwendungsbeobachtung wurden 2001 Patienten mit leichten Hirnleistungsstörungen (MCI) vor und nach der Gabe von zwei pflanzlichen Präparaten (Tebonin(R)(Ginkgo-biloba-Extrakt (EGb 761(R)) und Neuroplant(R)(Hypericum-Extrakt WS 5572(R)) bezüglich ihrer Lebensqualität und selbstberichteten kognitiven Funktionsfähigkeit untersucht. Die Ergebnisse zeigen eine starke Beeinträchtigung der selbstberichteten Lebensqualität und kognitiven Kompetenz im Verhältnis zur Referenzpopulation in der Gruppe mit MCI und leichter Demenz zu Therapiebeginn und größere Beeinträchtigungen der Lebensqualität bei Patienten, die sowohl hinsichtlich kognitiver Defizite (erfasst über Mini Mental Status Test, MMST) als auch der Depressivität (erfasst über Geriatrische Depressions Skala, GDS) belastet sind. Unter Tebonin(R)- und Neuroplant(R)-Therapie verbessert sich die selbstberichtete Lebensqualität und kognitive Kompetenz signifikant, wobei die Änderungen bei den besonders beeinträchtigten Personen im GDS und MMST stark ausgeprägt sind. Selbstberichtete Lebensqualität und selbstberichtete kognitive Kompetenz korrelieren miteinander hoch und signifikant, und Veränderungen in der klinischen Symptomatik (gemessen über GDS und MMST) korrelieren mit der Veränderung in der Lebensqualität und kognitiven Kompetenz ebenfalls hoch und signifikant. Bei einer parallelisierten Gruppe von Patienten, die von den behandelnden Ärzte entweder der Neuroplant(R)- bzw. der Tebonin(R)-Gruppe zugewiesen worden waren, zeigten sich gleichförmige Verbesserungen bei beiden Therapieformen. Beeinträchtigungen von Lebensqualität und kognitiver Kompetenz sind bei Patienten mit leichten Hirnleistungsstörungen, abhängig vom Ausmaß der Beeinträchtigung, vorhanden. Nach Gabe von Tebonin(R)bzw. Neuroplant(R)zeigt sich eine Veränderung der Lebensqualität und der kognitiven Kompetenz, deren Rückführbarkeit auf die Medikation allerdings nicht hinreichend zu beurteilen ist, da es sich nicht um eine randomisierte klinische Studie handelt. Dennoch bestehen Hinweise darauf, dass sich die Lebensqualität und selbstberichtete kognitive Funktionsfähigkeit im Beobachtungszeitraum bessert.

Published
2006
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16. Mnestic Block Syndrome

Author

Markowitsch, Hans J., Kessler, Josef, Russ, Michael O., Frölich, Lutz, Schneider, Barbara, and Maurer, Konrad

Abstract

The case of a patient with largely preserved intelligence, but severe and persistent memory impairments is reported. FA, a 46-year-old patient with the diagnosis of prolonged depression was investigated repeatedly over a two year period with neuroradiological, neuropsychological, neuromonitoring and other methods. While no brain damage was detectable in FA, he manifested continued and severe anterograde and retrograde memory disorders together with an inhibition in his thinking processes. Otherwise, his intellectual capabilities were in the normal range, that is he was not pseudo-demented. Various approaches with drug treatment and psychotherapy failed to improve his condition. The condition is interpreted as ‘mnestic block syndrome’ and is considered to be related to an altered brain metabolism which may include changes in various transmitter and hormonal systems (GABA-agonists, glucocorticoids, acetylcholine). Whether depression contributes to this syndrome is uncertain from FA's cognitive performance, but may be a possibility.

Published
1999
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17. Effects of long-term recovery from transient cerebral ischemia in rat brain: Tissue levels of acetylcholine, monoamines, and their metabolites

Author

Frölich, Lutz, Dirr, Albrecht, Riederer, Peter, and Hoyer, Siegfried

Abstract

Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine, serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA) and choline were simultaneously determined in the corpus striatum of rats after 15 min. complete cerebral ischemia (CCI) and in different intervals (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were compared to respective sham-operated control animals. After 15 min. CCI acetylcholine concentration decreased to 15%, and dopamine concentration to 56% of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to 64% of the control values. Acetylcholine, dopamine, serotonin and choline concentrations were not changed significantly after reperfusion. The metabolites HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of reperfusion, additionally HVA was decreased both, after 72 and 96 hours of reperfusion. The data indicate that surprisingly little permanent damage could be caused by a 15 min. ischemia in the striatum. Tissue levels of the neurotransmitters appeared differentially altered but similarly regulated during ischemia and subsequent recirculation. Acetylcholine and dopamin levels decreased profoundly during ischemia. However, acetylcholine levels could be compensated rapidly during reperfusion, whereas the dopaminergic system showed a long-lasting change in its turnover rate. Although serotonin levels were unaffected by CCI, there was an increase of its presumed turnover rate during reperfusion.

Published
1993
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18. Reduced immunoreactivity of adenylyl cyclase in dementia of the Alzheimer type

Author

Yamamoto, Megumi, Ozawa, Hiroki, Saito, Toshikazu, Frölich, Lutz, Riederer, Peter, and Takahata, Naohiko

Abstract

THE amounts of three adenylyl cyclase (AC) subtypes In membranes from brain obtained post-mortem from patients with dementia of Alzheimer type (DAT) and controls were studied by Western blotting using poly-clonal antibodies. AC subtypes were characterized by preabsorption by complementary peptides, species difference, tissue distribution and by using AC-VI-transfected cells. Immunoreactivities of AC-I and AC-II subtypes, which are predominant in brain tissue were decreased 40.5 (p< 0.02) and 52.0 (p< 0.02), respectively in DAT compared with controls. No significant difference in immunoreactivity of AC-V/VI subtypes distributed in various other tissues was observed. Our results are the first to indicate that reduced levels of brain-specific AC subtypes occur in DAT.

Published
1996

19. P3 topography in psychiatry and psychopharmacology

Author

Maurer, Konrad, Dierks, Thomas, Strik, Werner K., and Frölich, Lutz

Abstract

Summary Endogenous components of event related potentials are of particular interest in psychiatric diseases because of their relations to cognitive and behavioral processes. We studied the topography of these potentials in order to find out whether there are different scalp distributions in schizophrenic and depressive patients in relation to the psychopathological state and compared to normal controls. Furthermore variations of the topographical scalp distribution of P300 in normal volunteers after administration of physostigmine and biperiden was investigated. We demonstrated a clear relationship of the P300 amplitude with the negative symptom axis and found different topographical scalp distributions in different groups and experimental conditions. Topography of event related potentials is therefore a promising field of investigation for a better understanding of psychiatric disorders.

Published
1990
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20. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua, Damotte, Vincent, Naj, Adam, Boland, Anne, Vronskaya, Maria, Lee, Sven, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Zompo, Maria, Fox, Nick, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph, Adams, Hieab, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer, Dombroski, Beth, Naranjo, Maria, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will, Meslage, Stéphane, Kornhuber, Johannes, White, Charles, Song, Yuenjoo, Barber, Robert, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L., Albert, Marilyn, Deyn, Peter, Gu, Wei, Himali, Jayanadra, Beekly, Duane, Squassina, Alessio, Hartmann, Annette, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa, Doody, Rachelle, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas, Benito, Yolanda, Holmes, Clive, Karamujić-Čomić, Hata, Frosch, Matthew, Thonberg, Hakan, Maier, Wolfgang, Roshchupkin, Gennady, Ghetti, Bernardino, Giedraitis, Vilmantas, Kawalia, Amit, Li, Shuo, Huebinger, Ryan, Kilander, Lena, Moebus, Susanne, Hernández, Isabel, Kamboh, M., Brundin, RoseMarie, Turton, James, Yang, Qiong, Katz, Mindy, Concari, Letizia, Lord, Jenny, Beiser, Alexa, Keene, C., Helisalmi, Seppo, Kloszewska, Iwona, Kukull, Walter, Koivisto, Anne, Lynch, Aoibhinn, Tarraga, Lluís, Larson, Eric, Haapasalo, Annakaisa, Lawlor, Brian, Mosley, Thomas, Lipton, Richard, Solfrizzi, Vincenzo, Gill, Michael, Longstreth, W., Montine, Thomas, Frisardi, Vincenza, Diez-Fairen, Monica, Rivadeneira, Fernando, Petersen, Ronald, Deramecourt, Vincent, Alvarez, Ignacio, Salani, Francesca, Ciaramella, Antonio, Boerwinkle, Eric, Reiman, Eric, Fievet, Nathalie, Rotter, Jerome, Reisch, Joan, Hanon, Olivier, Cupidi, Chiara, Uitterlinden, A., Royall, Donald, Dufouil, Carole, Maletta, Raffaele, Rojas, Itziar, Sano, Mary, Brice, Alexis, Cecchetti, Roberta, George-Hyslop, Peter, Ritchie, Karen, Tsolaki, Magda, Tsuang, Debby, Dubois, Bruno, Craig, David, Wu, Chuang-Kuo, Soininen, Hilkka, Avramidou, Despoina, Albin, Roger, Fratiglioni, Laura, Germanou, Antonia, Apostolova, Liana, Keller, Lina, Koutroumani, Maria, Arnold, Steven, Panza, Francesco, Gkatzima, Olymbia, Asthana, Sanjay, Hannequin, Didier, Whitehead, Patrice, Atwood, Craig, Caffarra, Paolo, Hampel, Harald, Quintela, Inés, Carracedo, Ángel, Lannfelt, Lars, Rubinsztein, David, Barnes, Lisa, Pasquier, Florence, Frölich, Lutz, Barral, Sandra, McGuinness, Bernadette, Beach, Thomas, Johnston, Janet, Becker, James, Passmore, Peter, Bigio, Eileen, Schott, Jonathan, Bird, Thomas, Warren, Jason, Boeve, Bradley, Lupton, Michelle, Bowen, James, Proitsi, Petra, Boxer, Adam, Powell, John, Burke, James, Kauwe, John, Burns, Jeffrey, Mancuso, Michelangelo, Buxbaum, Joseph, Bonuccelli, Ubaldo, Cairns, Nigel, McQuillin, Andrew, Cao, Chuanhai, Livingston, Gill, Carlson, Chris, Bass, Nicholas, Carlsson, Cynthia, Hardy, John, Carney, Regina, Bras, Jose, Carrasquillo, Minerva, Guerreiro, Rita, Allen, Mariet, Chui, Helena, Fisher, Elizabeth, Masullo, Carlo, Crocco, Elizabeth, DeCarli, Charles, Bisceglio, Gina, Dick, Malcolm, Ma, Li, Duara, Ranjan, Graff-Radford, Neill, Evans, Denis, Hodges, Angela, Faber, Kelley, Scherer, Martin, Fallon, Kenneth, Riemenschneider, Matthias, Fardo, David, Heun, Reinhard, Farlow, Martin, Kölsch, Heike, Ferris, Steven, Leber, Markus, Foroud, Tatiana, Heuser, Isabella, Galasko, Douglas, Giegling, Ina, Gearing, Marla, Hüll, Michael, Geschwind, Daniel, Gilbert, John, Morris, John, Green, Robert, Mayo, Kevin, Growdon, John, Feulner, Thomas, Hamilton, Ronald, Harrell, Lindy, Drichel, Dmitriy, Honig, Lawrence, Cushion, Thomas, Huentelman, Matthew, Hollingworth, Paul, Hulette, Christine, Hyman, Bradley, Marshall, Rachel, Jarvik, Gail, Meggy, Alun, Abner, Erin, Menzies, Georgina, Jin, Lee-Way, Leonenko, Ganna, Real, Luis, Jun, Gyungah, Baldwin, Clinton, Grozeva, Detelina, Karydas, Anna, Russo, Giancarlo, Kaye, Jeffrey, Kim, Ronald, Jessen, Frank, Kowall, Neil, Vellas, Bruno, Kramer, Joel, Vardy, Emma, LaFerla, Frank, Jöckel, Karl-Heinz, Lah, James, Dichgans, Martin, Leverenz, James, Mann, David, Levey, Allan, Pickering-Brown, Stuart, Lieberman, Andrew, Klopp, Norman, Lunetta, Kathryn, Wichmann, H-Erich, Lyketsos, Constantine, Morgan, Kevin, Marson, Daniel, Brown, Kristelle, Martiniuk, Frank, Medway, Christopher, Mash, Deborah, Nöthen, Markus, Masliah, Eliezer, Hooper, Nigel, McCormick, Wayne, Daniele, Antonio, McCurry, Susan, Bayer, Anthony, McDavid, Andrew, Gallacher, John, McKee, Ann, Bussche, Hendrik, Mesulam, Marsel, Brayne, Carol, Miller, Bruce, Riedel-Heller, Steffi, Miller, Carol, Miller, Joshua, Al-Chalabi, Ammar, Morris, John, Shaw, Christopher, Myers, Amanda, Wiltfang, Jens, O’Bryant, Sid, Olichney, John, Alvarez, Victoria, Parisi, Joseph, Singleton, Andrew, Paulson, Henry, Collinge, John, Perry, William, Mead, Simon, Peskind, Elaine, Cribbs, David, Rossor, Martin, Pierce, Aimee, Ryan, Natalie, Poon, Wayne, Nacmias, Benedetta, Potter, Huntington, Sorbi, Sandro, Quinn, Joseph, Sacchinelli, Eleonora, Raj, Ashok, Spalletta, Gianfranco, Raskind, Murray, Caltagirone, Carlo, Bossù, Paola, Orfei, Maria, Reisberg, Barry, Clarke, Robert, Reitz, Christiane, Smith, A, Ringman, John, Warden, Donald, Roberson, Erik, Wilcock, Gordon, Rogaeva, Ekaterina, Bruni, Amalia, Rosen, Howard, Gallo, Maura, Rosenberg, Roger, Ben-Shlomo, Yoav, Sager, Mark, Mecocci, Patrizia, Saykin, Andrew, Pastor, Pau, Cuccaro, Michael, Vance, Jeffery, Schneider, Julie, Schneider, Lori, Slifer, Susan, Seeley, William, Smith, Amanda, Sonnen, Joshua, Spina, Salvatore, Stern, Robert, Swerdlow, Russell, Tang, Mitchell, Tanzi, Rudolph, Trojanowski, John, Troncoso, Juan, Deerlin, Vivianna, Eldik, Linda, Vinters, Harry, Vonsattel, Jean, Weintraub, Sandra, Welsh-Bohmer, Kathleen, Wilhelmsen, Kirk, Williamson, Jennifer, Wingo, Thomas, Woltjer, Randall, Wright, Clinton, Yu, Chang-En, Yu, Lei, Saba, Yasaman, Pilotto, Alberto, Bullido, Maria, Peters, Oliver, Crane, Paul, Bennett, David, Bosco, Paola, Coto, Eliecer, Boccardi, Virginia, Jager, Phil, Lleo, Alberto, Warner, Nick, Lopez, Oscar, Ingelsson, Martin, Deloukas, Panagiotis, Cruchaga, Carlos, Graff, Caroline, Gwilliam, Rhian, Fornage, Myriam, Goate, Alison, Sanchez-Juan, Pascual, Kehoe, Patrick, Amin, Najaf, Ertekin-Taner, Nilifur, Berr, Claudine, Debette, Stéphanie, Love, Seth, Launer, Lenore, Younkin, Steven, Dartigues, Jean-Francois, Corcoran, Chris, Ikram, M., Dickson, Dennis, Nicolas, Gael, Campion, Dominique, Tschanz, JoAnn, Schmidt, Helena, Hakonarson, Hakon, Clarimon, Jordi, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay, Broeckhoven, Christine, O’Donovan, Michael, DeStefano, Anita, Jones, Lesley, Haines, Jonathan, Deleuze, Jean-Francois, Owen, Michael, Gudnason, Vilmundur, Mayeux, Richard, Escott-Price, Valentina, Psaty, Bruce, Ramirez, Alfredo, Wang, Li-San, Ruiz, Agustin, Duijn, Cornelia, Holmans, Peter, Seshadri, Sudha, Williams, Julie, Amouyel, Phillippe, Schellenberg, Gerard, Lambert, Jean-Charles, and Pericak-Vance, Margaret

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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23. Relation of Personality Traits in Patients with Oral Anticoagulant Therapy to Attitudes towards Treatment with Vitamin-K Antagonists.

Author

Harenberg, Job, Frölich, Lutz, Felten, Marie-Theres, and Weiss, Christel

Abstract

Harenberg: Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Consultancy, Honoraria; Roche Diagnostics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bayer Health Care: Consultancy, Honoraria.

Published
2009
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24. Stability of the INR in Relation to Personality Traits in Patients On Stable Oral Anticoagulant Therapy.

Author

Harenberg, Job, Weiss, Christel, Felten, Marie-Theres, and Frölich, Lutz

Abstract

Harenberg: Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Consultancy, Honoraria; Roche Diagnostics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bayer Health Care: Consultancy, Honoraria.

Published
2009
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