661 results on '"Zinman, Lorne"'
Search Results
2. SF2Former: Amyotrophic Lateral Sclerosis Identification From Multi-center MRI Data Using Spatial and Frequency Fusion Transformer
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Kushol, Rafsanjany, Luk, Collin C., Dey, Avyarthana, Benatar, Michael, Briemberg, Hannah, Dionne, Annie, Dupré, Nicolas, Frayne, Richard, Genge, Angela, Gibson, Summer, Graham, Simon J., Korngut, Lawrence, Seres, Peter, Welsh, Robert C., Wilman, Alan, Zinman, Lorne, Kalra, Sanjay, and Yang, Yee-Hong
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Electrical Engineering and Systems Science - Image and Video Processing ,Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder involving motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has turned into a prominent class of machine learning programs in computer vision and has been successfully employed to solve diverse medical image analysis tasks. However, deep learning-based methods applied to neuroimaging have not achieved superior performance in ALS patients classification from healthy controls due to having insignificant structural changes correlated with pathological features. Therefore, the critical challenge in deep models is to determine useful discriminative features with limited training data. By exploiting the long-range relationship of image features, this study introduces a framework named SF2Former that leverages vision transformer architecture's power to distinguish the ALS subjects from the control group. To further improve the network's performance, spatial and frequency domain information are combined because MRI scans are captured in the frequency domain before being converted to the spatial domain. The proposed framework is trained with a set of consecutive coronal 2D slices, which uses the pre-trained weights on ImageNet by leveraging transfer learning. Finally, a majority voting scheme has been employed to those coronal slices of a particular subject to produce the final classification decision. Our proposed architecture has been thoroughly assessed with multi-modal neuroimaging data using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of our proposed strategy in terms of classification accuracy compared with several popular deep learning-based techniques., Comment: 17 pages, 8 figures
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- 2023
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3. Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke
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Yu, Di, Liang, Nuanyi, Zebarth, Julia, Shen, Qing, Ozzoude, Miracle, Goubran, Maged, Rabin, Jennifer S, Ramirez, Joel, Scott, Christopher JM, Gao, Fuqiang, Bartha, Robert, Symons, Sean, Haddad, Seyyed Mohammad Hassan, Berezuk, Courtney, Tan, Brian, Kwan, Donna, Hegele, Robert A, Dilliott, Allison A, Nanayakkara, Nuwan D, Binns, Malcolm A, Beaton, Derek, Arnott, Stephen R, Lawrence‐Dewar, Jane M, Hassan, Ayman, Dowlatshahi, Dar, Mandzia, Jennifer, Sahlas, Demetrios, Casaubon, Leanne, Saposnik, Gustavo, Otoki, Yurika, Lanctôt, Krista L, Masellis, Mario, Black, Sandra E, Swartz, Richard H, Taha, Ameer Y, Swardfager, Walter, Rashkovan, Natalie, Abrahao, Agessandro, Zinman, Lorne, Bonnick, Alisia, Scott, Christopher, Holmes, Melissa, Adamo, Sabrina, Freedman, Morris, Zamyadi, Mojdeh, Arnott, Stephen, Binns, Malcolm, Raamana, Pradeep, Strother, Stephen, Sunderland, Kelly, Theyers, Athena, Uthirakumaran, Abiramy, Levine, Brian, Troyer, Angela, Strong, Michael, Kleinstiver, Peter, Borrie, Michael, Finger, Elizabeth, Shoesmith, Christen, Faria, Frederico, Montero‐Odasso, Manuel, Sarquis‐Adamson, Yanina, Black, Alanna, Dilliott, Allison Ann, Hegele, Rob, Robinson, John, Farhan, Sali, Bartha, Rob, Haddad, Hassan, Nanayakkara, Nuwan, Zou, Guangyong, Pasternak, Stephen, Orange, JB, Roberts, Angela, Jog, Mandar, Seitz, Dallas, Brien, Don, Chen, Ying, Coe, Brian, Munoz, Doug, McLaughlin, Paula, Peltsch, Alicia, Bronskill, Susan, Lou, Wendy, Kumar, Sanjeev, Pollock, Bruce, Rajji, Tarek, Tang‐Wai, David, and Tartaglia, Carmela
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Biomedical Imaging ,Stroke ,Brain Disorders ,Neurosciences ,Humans ,Linoleic Acid ,Oxylipins ,Epoxide Hydrolases ,Cerebral Small Vessel Diseases ,Magnetic Resonance Imaging ,Atrophy ,Water ,lacunar stroke ,oxylipin ,small vessel disease ,soluble epoxide hydrolase ,white matter hyperintensity ,ONDRI Investigators [Link] ,Cardiorespiratory Medicine and Haematology - Abstract
Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (β=0.251, P=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (β=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P
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- 2023
4. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study
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van den Berg, Leonard H, Rothstein, Jeffrey D, Shaw, Pamela J, Babu, Suma, Benatar, Michael, Bucelli, Robert C, Genge, Angela, Glass, Jonathan D, Hardiman, Orla, Libri, Vincenzo, Mobach, Theodore, Oskarsson, Björn, Pattee, Gary L, Ravits, John, Shaw, Christopher E, Weber, Markus, Zinman, Lorne, Jafar-nejad, Paymaan, Rigo, Frank, Lin, Luan, Ferguson, Toby A, Gotter, Anthony L, Graham, Danielle, Monine, Michael, Inra, Jennifer, Sinks, Susie, Eraly, Satish, Garafalo, Steve, and Fradette, Stephanie
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- 2024
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5. Video-Based Facial Movement Analysis in the Assessment of Bulbar Amyotrophic Lateral Sclerosis: Clinical Validation
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Guarin, Diego L., Taati, Babak, Abrahao, Agessandro, Zinman, Lorne, and Yunusova, Yana
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Purpose: Facial movement analysis during facial gestures and speech provides clinically useful information for assessing bulbar amyotrophic lateral sclerosis (ALS). However, current kinematic methods have limited clinical application due to the equipment costs. Recent advancements in consumer-grade hardware and machine/deep learning made it possible to estimate facial movements from videos. This study aimed to establish the clinical validity of a video-based facial analysis for disease staging classification and estimation of clinical scores. Method: Fifteen individuals with ALS and 11 controls participated in this study. Participants with ALS were stratified into early and late bulbar ALS groups based on their speaking rate. Participants were recorded with a three-dimensional (3D) camera (color + depth) while repeating a simple sentence 10 times. The lips and jaw movements were estimated, and features related to sentence duration and facial movements were used to train a machine learning model for multiclass classification and to predict the Amyotrophic Lateral Sclerosis Functional Rating Scale--Revised (ALSFRS-R) bulbar subscore and speaking rate. Results: The classification model successfully separated healthy controls, the early ALS group, and the late ALS group with an overall accuracy of 96.1%. Video-based features demonstrated a high ability to estimate the speaking rate (adjusted R[superscript 2] = 0.82) and a moderate ability to predict the ALSFRS-R bulbar subscore (adjusted R[superscript 2] = 0.55). Conclusions: The proposed approach based on a 3D camera and machine learning algorithms represents an easy-to-use and inexpensive system that can be included as part of a clinical assessment of bulbar ALS to integrate facial movement analysis with other clinical data seamlessly.
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- 2022
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6. Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
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Granit, Volkan, Steele, Julie, Levy, Wendy, Paredes, Maria Elena, Hernandez, Jessica, Bilsker, Martin, Szacka, Katarzyna, Ronert, Adam, Jablońska, Dorota, Łuczak, Alina Zuzanna, Chaverri, Delia, Janse van Mantgem, Mark R, Bunte, Tommy M, Broere, Bianca, de Fockert, Arianne, Sanchez-Tejerina, Daniel, Landabaso, Carmen, Calvo, Andrea, Moglia, Cristina, Manera, Umberto, Canosa, Antonio, Vasta, Rosario, Salamone, Paolina, Fuda, Giuseppe, DeMarco, Giovanni, Casale, Federico, ME Forsberg, Karin, Winroth, Ivar, Almgren Stenberg, Erica, Holmgren, Monica, Amador, Maria del Mar, Lenglet, Timothee, Querin, Giorgia, Coudoin, Sylvie, Pavlakis, Pantelis, Holzberg, Shara, Sideri, Riccardo, Marinou, Kalliopi, Czarnecki, Maciej, Ługiewicz, Renata, Biel-Czarnecka, Marta, Boczkowska, Marcelina, Schotte, Caroline, Vynckier, Jan, Van Daele, Sien, Claeys, Thomas, Delmotte, Koen, Swinnen, Bart, Serrien, Anouk, D'Hondt, Ann, Lamaire, Nikita, Debien, Elisa, Jones, Sarah, Vachon, Chris, Grogan, James, Solorzano, Guillermo, Crowell, Allison, Rakocevic, Goran, Wagoner, Mary, Alma, Osmanovic, Flavia, Wiehler, Sonja, Körner, Olivia, Schreiber-Katz, Camilla, Wohnrade, Anastasia, Sarikidi, Carola, Kassebaum, Chantal, Fischer, Adamo, Ashley, Turcotte, Nicole, Duncan, Jessie, Turner, Ivone, Elman, Lauren, Massie, Rami, Berube, Maxime, Saunders, Natalie, Salmon, Kristiana, Foucher, Juliette, Agessandro, Abrahao, Shirley, Pham, Jahan, Mookshah, Phung, Liane, Statland, Jeffrey, Jawdat, Omar, Dimachkie, Mazen, Pasnoor, Mamatha, Farmakidis, Constantine, Heim, Andrew, Lillig, Katie, Lackey, Alyssa, Weber, Markus, Kurz, Martina, Levine, Todd, Benatar, Michael, Hansen, Thomas, Rom, Dror, Geist, Marie A, Blaettler, Thomas, Camu, William, Kuzma-Kozakiewicz, Magdalena, van den Berg, Leonard H, Morales, Raul Juntas, Chio, Adriano, Andersen, Peter M, Pradat, Pierre-Francois, Lange, Dale, Van Damme, Philip, Mora, Gabriele, Grudniak, Mariusz, Elliott, Matthew, Petri, Susanne, Olney, Nicholas, Ladha, Shafeeq, Goyal, Namita A, Meyer, Thomas, Hanna, Michael G, Quinn, Colin, Genge, Angela, Zinman, Lorne, Jabari, Duaa, Shoesmith, Christen, Ludolph, Albert C, Neuwirth, Christoph, Nations, Sharon, Shefner, Jeremy M, Turner, Martin R, Wuu, Joanne, Bennett, Richard, Dang, Hoang, and Sundgreen, Claus
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- 2024
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7. White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases
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Ozzoude, Miracle, Varriano, Brenda, Beaton, Derek, Ramirez, Joel, Adamo, Sabrina, Holmes, Melissa F., Scott, Christopher J. M., Gao, Fuqiang, Sunderland, Kelly M., McLaughlin, Paula, Goubran, Maged, Kwan, Donna, Roberts, Angela, Bartha, Robert, Symons, Sean, Tan, Brian, Swartz, Richard H., Abrahao, Agessandro, Saposnik, Gustavo, Masellis, Mario, Lang, Anthony E., Marras, Connie, Zinman, Lorne, Shoesmith, Christen, Borrie, Michael, Fischer, Corinne E., Frank, Andrew, Freedman, Morris, Montero-Odasso, Manuel, Kumar, Sanjeev, Pasternak, Stephen, Strother, Stephen C., Pollock, Bruce G., Rajji, Tarek K., Seitz, Dallas, Tang-Wai, David F., Turnbull, John, Dowlatshahi, Dar, Hassan, Ayman, Casaubon, Leanne, Mandzia, Jennifer, Sahlas, Demetrios, Breen, David P., Grimes, David, Jog, Mandar, Steeves, Thomas D. L., Arnott, Stephen R., Black, Sandra E., Finger, Elizabeth, Rabin, Jennifer, and Tartaglia, Maria Carmela
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- 2023
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8. Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study
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Müller, Hans-Peter, Abrahao, Agessandro, Beaulieu, Christian, Benatar, Michael, Dionne, Annie, Genge, Angela, Frayne, Richard, Graham, Simon J., Gibson, Summer, Korngut, Lawrence, Luk, Collin, Welsh, Robert C., Zinman, Lorne, Kassubek, Jan, and Kalra, Sanjay
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- 2024
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9. Validating Automatic Diadochokinesis Analysis Methods across Dysarthria Severity and Syllable Task in Amyotrophic Lateral Sclerosis
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Tanchip, Chelsea, Guarin, Diego L., McKinlay, Scotia, Barnett, Carolina, Kalra, Sanjay, Genge, Angela, Korngut, Lawrence, Green, Jordan R., Berry, James, Zinman, Lorne, Yadollahi, Azadeh, Abrahao, Agessandro, and Yunusova, Yana
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Purpose: Oral diadochokinesis (DDK) is a standard dysarthria assessment task. To extract automatic and semi-automatic DDK measurements, numerous DDK analysis algorithms based on acoustic signal processing are available, including amplitude based, spectral based, and hybrid. However, these algorithms have been predominantly validated in individuals with no perceptible to mild dysarthria. The behavior of these algorithms across dysarthria severity is largely unknown. Likewise, these algorithms have not been tested equally for various syllable types. The goal of this study was to evaluate the performance of five common DDK algorithms as a function of dysarthria severity, considering syllable types. Method: We analyzed 282 DDK recordings of /ba/, /pa/, and /ta/ from 145 participants with amyotrophic lateral sclerosis. Recordings were stratified into mild, moderate, or severe dysarthria groups based on individual performance on the Speech Intelligibility Test. Analysis included manual and automatic estimation of the number of syllables, DDK rate, and cycle-to-cycle temporal variability (cTV). Validation metrics included Bland-Altman mixed-effects limits of agreement between manual and automatic syllable counts, recall and precision between manual and automatic syllable boundary detection, and Kendall's tau-b correlations between manual and algorithm-detected DDK rate and cTV. Results: The amplitude-based algorithm (absolute energy) yielded the strongest correlations with manual analysis across all severity groups for DDK rate ([tau][subscript b] = 0.7-0.84) and cTV ([tau][subscript b] = 0.7-0.84) and the narrowest limits of agreement (-5.92 to 7.12 syllable difference). Moreover, this algorithm also provided the highest mean recall and precision across severity groups for /ba/ and /pa/, but with significantly more variation for/ta/. Conclusions: Algorithms based on signal energy analysis appeared to be the most robust for DDK analysis across dysarthria severity and syllable types; however, it remains prone to error against severe dysarthria and alveolar syllable context. Further development is needed to address this important issue.
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- 2022
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10. Psychometric Properties of Rapid Word-Based Rate Measures in the Assessment of Bulbar Amyotrophic Lateral Sclerosis: Comparisons with Syllable-Based Rate Tasks
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Shellikeri, Sanjana, Marzouqah, Reeman, Brooks, Benjamin Rix, Zinman, Lorne, Green, Jordan R., and Yunusova, Yana
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Purpose: Rapid maximum performance repetition tasks have increasingly demonstrated their utility as clinimetric markers supporting diagnosis and monitoring of bulbar disease in amyotrophic lateral sclerosis (ALS). A recently developed protocol uses novel real-word repetitions instead of traditional nonword/syllable sequences in hopes of improving sensitivity to motor speech impairments by adding a phonological target constraint that would activate a greater expanse of the motor speech neuroanatomy. This study established the psychometric properties of this novel clinimetric protocol in its assessment of bulbar ALS and compared performance to traditional syllable sequence dysdiadochokinetic (DDK) tasks. Specific objectives were to (a) compare rates between controls and speakers with symptomatic versus presymptomatic bulbar disease, (b) characterize their discriminatory ability in detecting presymptomatic bulbar disease compared to healthy speech, (c) determine their articulatory movement underpinnings, and (d) establish within-individual longitudinal changes. Method: DDK and novel tongue ("ticker"--TAR) and labial ("pepper"--LAR) articulatory rates were compared between n = 18 speakers with presymptomatic bulbar disease, n = 10 speakers with symptomatic bulbar disease, and n = 13 healthy controls. Bulbar disease groups were determined by a previously validated speaking rate cutoff. Discriminatory ability was determined using receiver operating characteristic analysis. Within-individual change over time was characterized in a subset of 16 participants with available longitudinal data using linear mixed-effects models. Real-time articulatory movements of the tongue front, tongue dorsum, jaw, and lips were captured using 3-D electromagnetic articulography; effects of movement displacement and speed on clinimetric rates were determined using stepwise linear regressions. Results: All clinimetric rates (traditional DDK tasks and novel tasks) were reduced in speakers with symptomatic bulbar disease; only TAR was reduced in speakers with presymptomatic bulbar disease and was able to detect this group with an excellent discrimination ability (area under the curve = 0.83). Kinematic analyses revealed associations with expected articulators, greater motor complexity, and differential articulatory patterns for the novel real-word repetitions than their DDK counterparts. Only LAR significantly declined longitudinally over the disease course. Conclusion: Novel real-word clinimetric rate tasks evaluating tongue and labial articulatory dysfunction are valid and effective markers for early detection and tracking of bulbar disease in ALS.
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- 2021
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11. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias
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Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.
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- 2023
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12. Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases
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Ozzoude, Miracle, Varriano, Brenda, Beaton, Derek, Ramirez, Joel, Holmes, Melissa F., Scott, Christopher J. M., Gao, Fuqiang, Sunderland, Kelly M., McLaughlin, Paula, Rabin, Jennifer, Goubran, Maged, Kwan, Donna, Roberts, Angela, Bartha, Robert, Symons, Sean, Tan, Brian, Swartz, Richard H., Abrahao, Agessandro, Saposnik, Gustavo, Masellis, Mario, Lang, Anthony E., Marras, Connie, Zinman, Lorne, Shoesmith, Christen, Borrie, Michael, Fischer, Corinne E., Frank, Andrew, Freedman, Morris, Montero-Odasso, Manuel, Kumar, Sanjeev, Pasternak, Stephen, Strother, Stephen C., Pollock, Bruce G., Rajji, Tarek K., Seitz, Dallas, Tang-Wai, David F., Turnbull, John, Dowlatshahi, Dar, Hassan, Ayman, Casaubon, Leanne, Mandzia, Jennifer, Sahlas, Demetrios, Breen, David P., Grimes, David, Jog, Mandar, Steeves, Thomas D. L., Arnott, Stephen R., Black, Sandra E., Finger, Elizabeth, and Tartaglia, Maria Carmela
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- 2022
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13. Feasibility of a continuous, multi-sensor remote health monitoring approach in persons living with neurodegenerative disease
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Godkin, F. Elizabeth, Turner, Erin, Demnati, Youness, Vert, Adam, Roberts, Angela, Swartz, Richard H., McLaughlin, Paula M., Weber, Kyle S., Thai, Vanessa, Beyer, Kit B., Cornish, Benjamin, Abrahao, Agessandro, Black, Sandra E., Masellis, Mario, Zinman, Lorne, Beaton, Derek, Binns, Malcolm A., Chau, Vivian, Kwan, Donna, Lim, Andrew, Munoz, Douglas P., Strother, Stephen C., Sunderland, Kelly M., Tan, Brian, McIlroy, William E., and Van Ooteghem, Karen
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- 2022
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14. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD
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Pottier, Cyril, Ren, Yingxue, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, van Blitterswijk, Marka, DeJesus-Hernandez, Mariely, van Rooij, Jeroen GJ, Murray, Melissa E, Christopher, Elizabeth, McDonnell, Shannon K, Fogarty, Zachary, Batzler, Anthony, Tian, Shulan, Vicente, Cristina T, Matchett, Billie, Karydas, Anna M, Hsiung, Ging-Yuek Robin, Seelaar, Harro, Mol, Merel O, Finger, Elizabeth C, Graff, Caroline, Öijerstedt, Linn, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Prudlo, Johannes, Rizzu, Patrizia, Simon-Sanchez, Javier, Edbauer, Dieter, Roeber, Sigrun, Diehl-Schmid, Janine, Evers, Bret M, King, Andrew, Mesulam, M Marsel, Weintraub, Sandra, Geula, Changiz, Bieniek, Kevin F, Petrucelli, Leonard, Ahern, Geoffrey L, Reiman, Eric M, Woodruff, Bryan K, Caselli, Richard J, Huey, Edward D, Farlow, Martin R, Grafman, Jordan, Mead, Simon, Grinberg, Lea T, Spina, Salvatore, Grossman, Murray, Irwin, David J, Lee, Edward B, Suh, EunRan, Snowden, Julie, Mann, David, Ertekin-Taner, Nilufer, Uitti, Ryan J, Wszolek, Zbigniew K, Josephs, Keith A, Parisi, Joseph E, Knopman, David S, Petersen, Ronald C, Hodges, John R, Piguet, Olivier, Geier, Ethan G, Yokoyama, Jennifer S, Rissman, Robert A, Rogaeva, Ekaterina, Keith, Julia, Zinman, Lorne, Tartaglia, Maria Carmela, Cairns, Nigel J, Cruchaga, Carlos, Ghetti, Bernardino, Kofler, Julia, Lopez, Oscar L, Beach, Thomas G, Arzberger, Thomas, Herms, Jochen, Honig, Lawrence S, Vonsattel, Jean Paul, Halliday, Glenda M, Kwok, John B, White, Charles L, Gearing, Marla, Glass, Jonathan, Rollinson, Sara, Pickering-Brown, Stuart, Rohrer, Jonathan D, Trojanowski, John Q, Van Deerlin, Vivianna, Bigio, Eileen H, Troakes, Claire, Al-Sarraj, Safa, Asmann, Yan, Miller, Bruce L, Graff-Radford, Neill R, Boeve, Bradley F, and Seeley, William W
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Biomedical and Clinical Sciences ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Clinical Research ,Brain Disorders ,Rare Diseases ,Human Genome ,Alzheimer's Disease Related Dementias (ADRD) ,Dementia ,Prevention ,Genetics ,Frontotemporal Dementia (FTD) ,Neurodegenerative ,Acquired Cognitive Impairment ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Aged ,DNA Repeat Expansion ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,Female ,Frontal Lobe ,Frontotemporal Lobar Degeneration ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,HLA-DQ Antigens ,Humans ,Intracellular Signaling Peptides and Proteins ,Loss of Function Mutation ,Male ,Middle Aged ,Nerve Tissue Proteins ,Potassium Channels ,Progranulins ,Protein Serine-Threonine Kinases ,Proteins ,RNA ,Messenger ,Risk Factors ,Sequence Analysis ,RNA ,Societies ,Scientific ,TDP-43 Proteinopathies ,White People ,Whole-genome sequencing FTLD-TDP ,TBK1 ,DPP6 ,UNC13A ,HLA ,Immunity ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (p value = 4.82e - 08, OR = 2.12), and two known loci: UNC13A, led by rs1297319 (p value = 1.27e - 08, OR = 1.50) and HLA-DQA2 led by rs17219281 (p value = 3.22e - 08, OR = 1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole-genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n ≥ 3) as compared to controls (n = 0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g., DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis.
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- 2019
15. Rate of speech decline in individuals with amyotrophic lateral sclerosis
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Eshghi, Marziye, Yunusova, Yana, Connaghan, Kathryn P., Perry, Bridget J., Maffei, Marc F., Berry, James D., Zinman, Lorne, Kalra, Sanjay, Korngut, Lawrence, Genge, Angela, Dionne, Annie, and Green, Jordan R.
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- 2022
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16. Accessing and Receiving Speech-Language Pathology Services at the Multidisciplinary Amyotrophic Lateral Sclerosis Clinic: An Exploratory Qualitative Study of Patient Experiences and Needs.
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Huynh, Anna, Adams, Kerry, Barnett-Tapia, Carolina, Kalra, Sanjay, Zinman, Lorne, and Yunusova, Yana
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Purpose: This study sought to explore how patients with amyotrophic lateral sclerosis (ALS) presenting with coexisting bulbar and cognitive impairments and their caregivers experienced the speech-language pathologist (SLP) services provided in multidisciplinary ALS clinics in Canada and identified their perceived needs for bulbar symptom management. Method: This qualitative study was informed by interpretive description. Seven interviews were conducted with patients with severe bulbar dysfunction or severe bulbar and cognitive dysfunction due to ALS or ALS-frontotemporal dementia, respectively, and/or their caregivers. Purposive sampling was used to recruit individuals with severe bulbar or bulbar and cognitive disease. Thematic analysis was used to analyze interview data. Results: Patients and caregivers reported difficulties with accessing and receiving SLP services at the multidisciplinary ALS clinic. These difficulties were further exacerbated in those with severe cognitive disease. Participants expressed a need for more specific (i.e., disease and service-related) information and personalized care to address their changing needs and preferences. Engaging caregivers earlier in SLP appointments was perceived as vital to support care planning and provide in-time caregiver education. Conclusions: This study highlighted the challenges experienced by patients and caregivers in accessing and receiving SLP services. There is a pressing need for a more person-centered approach to ALS care and a continuing need for education of SLPs on care provision in cases of complex multisymptom diseases within a multidisciplinary ALS clinic. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis.
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Guo, Jingyan, You, Linya, Zhou, Yu, Hu, Jiali, Li, Jiahao, Yang, Wanli, Tang, Xuelin, Sun, Yimin, Gu, Yuqi, Dong, Yi, Chen, Xi, Sato, Christine, Zinman, Lorne, Rogaeva, Ekaterina, Wang, Jian, Chen, Yan, and Zhang, Ming
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AMYOTROPHIC lateral sclerosis ,GENE expression ,MOTOR neuron diseases ,GENOMICS ,WHOLE genome sequencing - Abstract
Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell–cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk. [ABSTRACT FROM AUTHOR]
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- 2024
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18. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.
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Zhang, Ming, Ferrari, Raffaele, Tartaglia, Maria Carmela, Keith, Julia, Surace, Ezequiel I, Wolf, Uri, Sato, Christine, Grinberg, Mark, Liang, Yan, Xi, Zhengrui, Dupont, Kyle, McGoldrick, Philip, Weichert, Anna, McKeever, Paul M, Schneider, Raphael, McCorkindale, Michael D, Manzoni, Claudia, Rademakers, Rosa, Graff-Radford, Neill R, Dickson, Dennis W, Parisi, Joseph E, Boeve, Bradley F, Petersen, Ronald C, Miller, Bruce L, Seeley, William W, van Swieten, John C, van Rooij, Jeroen, Pijnenburg, Yolande, van der Zee, Julie, Van Broeckhoven, Christine, Le Ber, Isabelle, Van Deerlin, Vivianna, Suh, EunRan, Rohrer, Jonathan D, Mead, Simon, Graff, Caroline, Öijerstedt, Linn, Pickering-Brown, Stuart, Rollinson, Sara, Rossi, Giacomina, Tagliavini, Fabrizio, Brooks, William S, Dobson-Stone, Carol, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Binetti, Giuliano, Benussi, Luisa, Ghidoni, Roberta, Nacmias, Benedetta, Sorbi, Sandro, Bruni, Amalia C, Galimberti, Daniela, Scarpini, Elio, Rainero, Innocenzo, Rubino, Elisa, Clarimon, Jordi, Lleó, Alberto, Ruiz, Agustin, Hernández, Isabel, Pastor, Pau, Diez-Fairen, Monica, Borroni, Barbara, Pasquier, Florence, Deramecourt, Vincent, Lebouvier, Thibaud, Perneczky, Robert, Diehl-Schmid, Janine, Grafman, Jordan, Huey, Edward D, Mayeux, Richard, Nalls, Michael A, Hernandez, Dena, Singleton, Andrew, Momeni, Parastoo, Zeng, Zhen, Hardy, John, Robertson, Janice, Zinman, Lorne, Rogaeva, Ekaterina, and International FTD-Genomics Consortium (IFGC)
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International FTD-Genomics Consortium ,Humans ,Amyotrophic Lateral Sclerosis ,Age of Onset ,DNA Methylation ,Gene Expression Regulation ,CpG Islands ,Genotype ,Heterozygote ,Polymorphism ,Single Nucleotide ,Aged ,Middle Aged ,Female ,Male ,Frontotemporal Dementia ,C9orf72 Protein ,C9orf72 ,genetic association ,age of onset ,amyotrophic lateral sclerosis ,frontotemporal dementia ,Polymorphism ,Single Nucleotide ,Neurology & Neurosurgery ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
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- 2018
19. Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study.
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Schneider, Raphael, McKeever, Paul, Kim, TaeHyung, Graff, Caroline, van Swieten, John Cornelis, Karydas, Anna, Boxer, Adam, Rosen, Howie, Miller, Bruce L, Laforce, Robert, Galimberti, Daniela, Masellis, Mario, Borroni, Barbara, Zhang, Zhaolei, Zinman, Lorne, Rohrer, Jonathan Daniel, Tartaglia, Maria Carmela, Robertson, Janice, and Genetic FTD Initiative (GENFI)
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Genetic FTD Initiative ,Humans ,tau Proteins ,MicroRNAs ,Down-Regulation ,Female ,Male ,Exosomes ,Frontotemporal Dementia ,Biomarkers ,Dementia ,Neurodegenerative ,Rare Diseases ,Genetics ,Brain Disorders ,Acquired Cognitive Impairment ,Biotechnology ,Alzheimer's Disease Related Dementias (ADRD) ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aging ,Alzheimer's Disease ,Prevention ,Neurosciences ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,Neurology & Neurosurgery ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
ObjectiveTo determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD.MethodsGENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age.ResultsIn the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98).ConclusionsExosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
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- 2018
20. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial
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Kiernan, Matthew, Mathers, Susan, Henderson, Robert, Needham, Merrilee, Schultz, David, Löscher, Wolfgang, Mitrovic, Nenad, Rath, Jakob, Damme, Philip Van, De Bleecker, Jan L., Delstanche, Stéphanie, Johnston, Wendy, Zinman, Lorne, O'Connell, Colleen, Matte, Genevieve, Dionne, Annie, Korngut, Lawrence, Turnbull, John, Laaksovirta, Hannu, Jokela, Manu, Tapiola, Tero, Soriani, Marie-Hélène, Couratier, Philippe, Camu, William, Corcia, Philippe, Ludolph, Albert, Großkreutz, Julian, Meyer, Thomas, Boentert, Matthias, Schrank, Berthold, Prudlo, Johannes, Untucht, Robert, Hardiman, Orla, Siciliano, Gabriele, Chio', Adriano, Mazzini, Letizia, Inghilleri, Maurizio, Caponnetto, Claudia, Mora, Gabriele, Mora Pardina, Jesús S, Farrero Munoz, Eva, Vázquez Costa, Juan F, Aguera Morales, Eduardo, Varona, Luis, Andersen, Peter, Ingre, Caroline, Johansson, Rune, Radunovic, Aleksandar, Young, Carolyn, Babu, Suma, Shaibani, Aziz, Staff, Nathan, Vu, Tuan, Rivner, Michael, Scelsa, Stephen, Sivakumar, Kumaraswamy, Waheed, Waqar, Heitzman, Daragh, Rana, Sandeep, Pattee, Gary, Ajroud-Driss, Senda, Bayat, Elham, Kasarskis, Edward, Lange, Dale J, Elliott, Michael, Harris, Brent, Felice, Kevin, Pulley, Michael T, Kwan, Justin, Brown, Martin, Ravits, John, Burford, Matthew, Karam, Chafic, Miller, Timothy, Andrews, Jinsy, Levine, Todd, Locatelli, Eduardo, Wymer, James, Bedlack, Richard, Fee, Dominic, Goyal, Namita, Oskarsson, Bjorn, McCluskey, Leo, Caress, James, Weiss, Michael, Quick, Adam, Bromberg, Mark, Lacomis, David, Goutman, Stephen, Rezania, Kourosh, Guliani, Gaurav, Goslin, Kimberly, Katz, Jonathan S, Cudkowicz, Merit, Genge, Angela, Maragakis, Nicholas, Petri, Susanne, van den Berg, Leonard, Aho, Valtteri V, Sarapohja, Toni, Kuoppamäki, Mikko, Garratt, Chris, and Al-Chalabi, Ammar
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- 2021
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21. MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease
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Strong, Michael, Kleinstiver, Peter, Rashkovan, Natalie, Bronskill, Susan, Black, Sandra E., Borrie, Michael, Finger, Elizabeth, Fischer, Corinne, Frank, Andrew, Freedman, Morris, Kumar, Sanjeev, Pasternak, Stephen, Pollock, Bruce, Rajji, Tarek, Seitz, Dallas, Tang-Wai, David, Tartaglia, Carmela, Varriano, Brenda, Abrahao, Agessandro, Chum, Marvin, Shoesmith, Christen, Turnbull, John, Zinman, Lorne, Lawrence-Dewar, Jane, Kwan, Donna, Tan, Brian, Fraser, Julia, McIlroy, Bill, Cornish, Ben, Van Ooteghem, Karen, Faria, Frederico, Montero-Odasso, Manuel, Sarquis-Adamson, Yanina, Black, Alanna, Greenberg, Barry, Hatch, Wendy, Hudson, Chris, Leontieva, Elena, Margolin, Ed, Mandelcorn, Efrem, Tayyari, Faryan, Defrawy, Sherif, Brien, Don, Chen, Ying, Coe, Brian, Munoz, Doug, Bonnick, Alisia, Casaubon, Leanne, Dowlatshahi, Dar, Hassan, Ayman, Mandzia, Jennifer, Sahlas, Demetrios, Saposnik, Gustavo, Swartz, Richard H., Breen, David, Grimes, David, Jog, Mandar, Lang, Anthony, Marras, Connie, Masellis, Mario, Steeves, Tom, Bulman, Dennis, Dilliott, Allison Ann, Ghani, Mahdi, Hegele, Rob, Robinson, John, Rogaeva, Ekaterina, Farhan, Sali, Bartha, Rob, Haddad, Hassan, Nanayakkara, Nuwan, Ramirez, Joel, Scott, Christopher, Symons, Sean, Berezuk, Courtney, Holmes, Melissa, Adamo, Sabrina, Ozzoude, Miracle, Zamyadi, Mojdeh, Arnott, Stephen, Beaton, Derek, Binns, Malcolm, Lou, Wendy, Raamana, Pradeep, Strother, Stephen, Sunderland, Kelly, Theyers, Athena, Uthirakumaran, Abiramy, Zou, Guangyong (GY), Sujanthan, Sujeevini, Munoz, David, Dixon, Roger A., Woulfe, John, Levine, Brian, McLaughlin, Paula, Orange, J.B., Peltsch, Alicia, Roberts, Angela, Troyer, Angela, Holmes, Melissa F., Scott, Christopher J.M., Gao, Fuqiang, Yu, Di, Swardfager, Walter, Boulos, Mark I., Murray, Brian J., Bartha, Robert, and Lim, Andrew
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- 2021
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22. Defining SOD1 ALS natural history to guide therapeutic clinical trial design
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Bali, Taha, Self, Wade, Liu, Jingxia, Siddique, Teepu, Wang, Leo H, Bird, Thomas D, Ratti, Elena, Atassi, Nazem, Boylan, Kevin B, Glass, Jonathan D, Maragakis, Nicholas J, Caress, James B, McCluskey, Leo F, Appel, Stanley H, Wymer, James P, Gibson, Summer, Zinman, Lorne, Mozaffar, Tahseen, Callaghan, Brian, McVey, April L, Jockel-Balsarotti, Jennifer, Allred, Peggy, Fisher, Elena R, Lopate, Glenn, Pestronk, Alan, Cudkowicz, Merit E, and Miller, Timothy M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Neurosciences ,ALS ,Rare Diseases ,Clinical Research ,Neurodegenerative ,Clinical Trials and Supportive Activities ,Adult ,Age of Onset ,Amyotrophic Lateral Sclerosis ,Clinical Trials as Topic ,Disease Progression ,Humans ,Middle Aged ,Mutation ,Research Design ,Retrospective Studies ,Superoxide Dismutase ,Vital Capacity ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences - Abstract
ImportanceUnderstanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population.ObjectiveTo establish an updated natural history of ALSSOD1.Design, setting and participantsRetrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.Main outcomes and measuresAge of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis.ResultsMean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p
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- 2017
23. Texture classification of MR images of the brain in ALS using M-CoHOG: A multi-center study
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E Elahi, G.M. Mashrur, Kalra, Sanjay, Zinman, Lorne, Genge, Angela, Korngut, Lawrence, and Yang, Yee-Hong
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- 2020
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24. Single-nucleus multiomic atlas of frontal cortex in amyotrophic lateral sclerosis with a deep learning-based decoding of alternative polyadenylation mechanisms
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McKeever, Paul M., primary, Sababi, Aiden M., additional, Sharma, Raghav, additional, Khuu, Nicholas, additional, Xu, Zhiyu, additional, Shen, Shu Yi, additional, Xiao, Shangxi, additional, McGoldrick, Philip, additional, Orouji, Elias, additional, Ketela, Troy, additional, Sato, Christine, additional, Moreno, Danielle, additional, Visanji, Naomi, additional, Kovacs, Gabor G., additional, Keith, Julia, additional, Zinman, Lorne, additional, Rogaeva, Ekaterina, additional, Goodarzi, Hani, additional, Bader, Gary, additional, and Robertson, Janice, additional
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- 2023
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25. Phase 3B study evaluating superiority of daily dosing vs approved on/off oral edaravone dosing over 48 weeks in patients with amyotrophic lateral sclerosis (MT-1186-A02)
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Salah, Alejandro, primary, Desilva, Shari, additional, Zinman, Lorne, additional, Chum, Marvin, additional, Chio, Adriano, additional, Ludolph, Albert C., additional, Sobue, Gen, additional, Doyu, Manabu, additional, Selness, Daniel, additional, Todorovic, Vesna, additional, Hirai, Manabu, additional, Wamil, Art, additional, and Apple, Stephen, additional
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- 2023
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26. Neuroinflammatory biomarkers in neurodegenerative disease: Insights from the ONDRI Cohort
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Sumra, Vishaal, primary, Dilliott, Allison Ann, additional, Frank, Andrew R, additional, Lang, Anthony E, additional, Roberts, Angela C, additional, Troyer, Angela, additional, Levine, Brian, additional, Arnott, Stephen R., additional, Tan, Brian, additional, Fischer, Corinne E., additional, Marras, Connie, additional, Kwan, Donna, additional, Munoz, Douglas, additional, Tang‐Wai, David F., additional, Finger, Elizabeth, additional, Rogaeva, Ekaterina, additional, Orange, Joseph B, additional, Ramirez, Joel, additional, Sunderland, Kelly M, additional, Zinman, Lorne, additional, Binns, Malcolm, additional, Borrie, Michael, additional, Masellis, Mario, additional, Freedman, Morris, additional, Montero‐Odasso, Manuel, additional, Ozzoude, Miracle, additional, Bartha, Robert, additional, Swartz, Richard H., additional, and Tartaglia, Carmela, additional
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- 2023
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27. Treatment outcomes for patients with amyotrophic lateral sclerosis receiving intravenous edaravone from a home and alternative-site infusion provider
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Abrahão, Agessandro, primary, Da Silva, Polina, additional, Ciepielewska, Malgorzata, additional, Do, Quan, additional, Ortlip, Kayla Janovsky, additional, Martin, Karen, additional, and Zinman, Lorne, additional
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- 2023
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28. Assessing the impact of falls on neuropsychiatric symptoms in patients with neurodegenerative disease
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Joghataie, Goldin, primary, Dilliott, Allison Ann, additional, Frank, Andrew R, additional, Lang, Anthony E, additional, Roberts, Angela C, additional, Troyer, Angela, additional, Levine, Brian, additional, Arnott, Stephen R., additional, Tan, Brian, additional, Fischer, Corinne E., additional, Marras, Connie, additional, Kwan, Donna, additional, Munoz, Douglas, additional, Tang‐Wai, David F., additional, Finger, Elizabeth, additional, Rogaeva, Ekaterina, additional, Orange, Joseph B, additional, Ramirez, Joel, additional, Sunderland, Kelly M, additional, Zinman, Lorne, additional, Binns, Malcolm, additional, Borrie, Michael, additional, Masellis, Mario, additional, Freedman, Morris, additional, Montero‐Odasso, Manuel, additional, Ozzoude, Miracle, additional, Bartha, Robert, additional, Swartz, Richard H., additional, Abrahao, Agessandro, additional, McIlroy, Bill, additional, Strong, Michael J., additional, and Tartaglia, Carmela, additional
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- 2023
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29. Corrigendum to: “Generation of five induced pluripotent stem cells lines from four members of the same family carrying a C9orf72 repeat expansion and one wild-type member” [Stem Cell Res. 66 (2023) 1–5/102998]
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Lattuada, Chiara, primary, Santangelo, Serena, additional, Peverelli, Silvia, additional, McGoldrick, Philip, additional, Rogaeva, Ekaterina, additional, Zinman, Lorne, additional, Haase, Georg, additional, Géli, Vincent, additional, Silani, Vincenzo, additional, Robertson, Janice, additional, Ratti, Antonia, additional, and Bossolasco, Patrizia, additional
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- 2023
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30. Phase 3B extension study evaluating superiority of daily vs approved on/off oral edaravone dosing in patients with amyotrophic lateral sclerosis
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Rothstein, Jeffrey, primary, Desilva, Shari, additional, Zinman, Lorne, additional, Chum, Marvin, additional, Chio, Adriano, additional, Ludolph, Albert C., additional, Sobue, Gen, additional, Doyu, Manabu, additional, Selness, Daniel, additional, Todorovic, Vesna, additional, Hirai, Manabu, additional, Fumihiro, Takahashi, additional, Wamil, Art, additional, Salah, Alejandro, additional, and Apple, Stephen, additional
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- 2023
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31. Combined epigenetic/genetic study identified an ALS age of onset modifier
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Zhang, Ming, Xi, Zhengrui, Saez-Atienzar, Sara, Chia, Ruth, Moreno, Danielle, Sato, Christine, Montazer Haghighi, Mahdi, Traynor, Bryan J., Zinman, Lorne, and Rogaeva, Ekaterina
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- 2021
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32. DNA methylation age acceleration is associated with ALS age of onset and survival
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Zhang, Ming, McKeever, Paul M., Xi, Zhengrui, Moreno, Danielle, Sato, Christine, Bergsma, Tessa, McGoldrick, Philip, Keith, Julia, Robertson, Janice, Zinman, Lorne, and Rogaeva, Ekaterina
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- 2020
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33. Kinematic Features of Jaw and Lips Distinguish Symptomatic from Presymptomatic Stages of Bulbar Decline in Amyotrophic Lateral Sclerosis
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Bandini, Andrea, Green, Jordan R., Wang, Jun, Campbell, Thomas F., Zinman, Lorne, and Yunusova, Yana
- Abstract
Purpose: The goals of this study were to (a) classify speech movements of patients with amyotrophic lateral sclerosis (ALS) in presymptomatic and symptomatic phases of bulbar function decline relying solely on kinematic features of lips and jaw and (b) identify the most important measures that detect the transition between early and late bulbar changes. Method: One hundred ninety-two recordings obtained from 64 patients with ALS were considered for the analysis. Feature selection and classification algorithms were used to analyze lip and jaw movements recorded with Optotrak Certus (Northern Digital Inc.) during a sentence task. A feature set, which included 35 measures of movement range, velocity, acceleration, jerk, and area measures of lips and jaw, was used to classify sessions according to the speaking rate into presymptomatic (> 160 words per minute) and symptomatic (< 160 words per minute) groups. Results: Presymptomatic and symptomatic phases of bulbar decline were distinguished with high accuracy (87%), relying only on lip and jaw movements. The best features that allowed detecting the differences between early and later bulbar stages included cumulative path of lower lip and jaw, peak values of velocity, acceleration, and jerk of lower lip and jaw. Conclusion: The results established a relationship between facial kinematics and bulbar function decline in ALS. Considering that facial movements can be recorded by means of novel inexpensive and easy-to-use, video-based methods, this work supports the development of an automatic system for facial movement analysis to help clinicians in tracking the disease progression in ALS.
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- 2018
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34. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial
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Cudkowicz, Merit E, Titus, Sarah, Kearney, Marianne, Yu, Hong, Sherman, Alexander, Schoenfeld, David, Hayden, Douglas, Shui, Amy, Brooks, Benjamin, Conwit, Robin, Felsenstein, Donna, Greenblatt, David J, Keroack, Myles, Kissel, John T, Miller, Robert, Rosenfeld, Jeffrey, Rothstein, Jeffrey D, Simpson, Ericka, Tolkoff-Rubin, Nina, Zinman, Lorne, Shefner, Jeremy M, and Investigators, for the Ceftriaxone Study
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Neurosciences ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Amyotrophic Lateral Sclerosis ,Ceftriaxone ,Double-Blind Method ,Dyspnea ,Female ,Humans ,Male ,Middle Aged ,Treatment Outcome ,Ceftriaxone Study Investigators ,Neurology & Neurosurgery ,Clinical sciences - Abstract
BackgroundGlutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.MethodsThis three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.FindingsStage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, -0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p
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- 2014
35. Recommandations canadiennes pour les pratiques optimales de prise en charge de la sclerose laterale amyotrophique
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Shoesmith, Christen, Abrahao, Agessandro, Benstead, Tim, Chum, Marvin, Dupre, Nicolas, Izenberg, Aaron, Johnston, Wendy, Kalra, Sanjay, Leddin, Desmond, O'Connell, Colleen, Schellenberg, Kerri, Tandon, Anu, and Zinman, Lorne
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Amyotrophic lateral sclerosis -- Diagnosis -- Care and treatment ,Therapeutics -- Standards -- Practice ,Medical care quality -- Standards ,Health - Abstract
La sclerose laterale amyotrophique (SLA) est une maladie progressive invalidante due a une degenerescence des motoneurones dans le cerveau et la moelle epiniere; elle provoque faiblesse, atrophie musculaire, fasciculations et [...]
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- 2020
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36. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis
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Shoesmith, Christen, Abrahao, Agessandro, Benstead, Tim, Chum, Marvin, Dupre, Nicolas, Izenberg, Aaron, Johnston, Wendy, Kalra, Sanjay, Leddin, Desmond, OConnell, Colleen, Schellenberg, Kerri, Tandon, Anu, and Zinman, Lorne
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Amyotrophic lateral sclerosis -- Diagnosis -- Care and treatment ,Practice guidelines (Medicine) -- Evaluation ,Health - Abstract
Amyotrophic lateral sclerosis (ALS) is a debilitating, progressive disease with degeneration of motor neurons in the brain and spinal cord causing weakness, muscle atrophy, fasciculations and spasticity. (1) Onset in [...]
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- 2020
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37. Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.
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Sakurai, Ryota, Pieruccini‐Faria, Frederico, Cornish, Benjamin, Fraser, Julia, Binns, Malcolm A., Beaton, Derek, Dilliott, Allison Ann, Kwan, Donna, Ramirez, Joel, Tan, Brian, Scott, Christopher J. M., Sunderland, Kelly M., Tartaglia, Carmela, Finger, Elizabeth, Zinman, Lorne, Freedman, Morris, McLaughlin, Paula M., Swartz, Richard H., Symons, Sean, and Lang, Anthony E.
- Abstract
INTRODUCTION: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non‐APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain‐specific poorer cognitive performances, mediated by smaller gray matter volume. DISCUSSION: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. Highlights: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases.Slow gait and smaller gray matter volumes are associated, independently of APOE E4.Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume.Gait slowness in APOE E4 carriers indicates poorer cognition‐related brain changes. [ABSTRACT FROM AUTHOR]
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- 2024
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38. SF2Former: Amyotrophic lateral sclerosis identification from multi-center MRI data using spatial and frequency fusion transformer
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Kushol, Rafsanjany, primary, Luk, Collin C., additional, Dey, Avyarthana, additional, Benatar, Michael, additional, Briemberg, Hannah, additional, Dionne, Annie, additional, Dupré, Nicolas, additional, Frayne, Richard, additional, Genge, Angela, additional, Gibson, Summer, additional, Graham, Simon J., additional, Korngut, Lawrence, additional, Seres, Peter, additional, Welsh, Robert C., additional, Wilman, Alan H., additional, Zinman, Lorne, additional, Kalra, Sanjay, additional, and Yang, Yee-Hong, additional
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- 2023
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39. Amyotrophic Lateral Sclerosis–Bulbar Dysfunction Index–Remote: Test–Retest and Interrater Reliability of Candidate Items
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Bouvier, Liziane, primary, Green, Jordan R., additional, Tapia, Carolina Barnett, additional, Tilton-Bolowsky, Victoria, additional, Maffei, Marc F., additional, Fless, Zuzana, additional, Seaver, Katie, additional, Huynh, Anna, additional, Gutz, Sarah E., additional, Martino, Rosemary, additional, Abrahao, Agessandro, additional, Berry, James, additional, Zinman, Lorne, additional, and Yunusova, Yana, additional
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- 2023
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40. Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease
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Sulistyo, Adrienne, additional, Abrahao, Agessandro, additional, Freitas, Maria Eliza, additional, Ritsma, Benjamin, additional, and Zinman, Lorne, additional
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- 2023
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41. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, Georgios, Appel, Stanley H., Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard, Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Allen, Andrew S., Appel, Stanley, Bedlack, Richard S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, D’Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Mazzini, Letizia, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A. Nazli, Blair, Ian P., Chio, Adriano, Cooper-Knock, Jonathan, de Carvalho, Mamede, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Kooyman, Maarten, Landers, John, McLaughlin, Russell, Middelkoop, Bas, Mill, Jonathan, Neto, Miguel Mitne, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shatunov, Aleksey, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Weber, Markus, Williams, Kelly L., Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., Murphy, Natalie A., van Vugt, Joke J.F.A., Geiger, Joshua T., Van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Messina, Sonia, Simone, Isabella L., Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Wyman, Stacia K., LeNail, Alex, Van Eyk, Jennifer E., Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L.M.A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J.L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Van Eijk, Kristel R., Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Fifita, Jennifer A., Nicholson, Garth A., Esteban-Pérez, Jesús, García-Redondo, Alberto, Rogaeva, Ekaterina, Zinman, Lorne, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Van Damme, Philip, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.
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- 2018
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42. Neuropathologic description of CHCHD10 mutated amyotrophic lateral sclerosis
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Keith, Julia L., Swinkin, Emily, Gao, Andrew, Alminawi, Samira, Zhang, Ming, McGoldrick, Philip, McKeever, Paul, Robertson, Janice, Rogaeva, Ekaterina, and Zinman, Lorne
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- 2020
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43. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias
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Kaivola, Karri, primary, Chia, Ruth, additional, Ding, Jinhui, additional, Rasheed, Memoona, additional, Fujita, Masashi, additional, Menon, Vilas, additional, Walton, Ronald L., additional, Collins, Ryan L., additional, Billingsley, Kimberley, additional, Brand, Harrison, additional, Talkowski, Michael, additional, Zhao, Xuefang, additional, Dewan, Ramita, additional, Stark, Ali, additional, Ray, Anindita, additional, Solaiman, Sultana, additional, Alvarez Jerez, Pilar, additional, Malik, Laksh, additional, Dawson, Ted M., additional, Rosenthal, Liana S., additional, Albert, Marilyn S., additional, Pletnikova, Olga, additional, Troncoso, Juan C., additional, Masellis, Mario, additional, Keith, Julia, additional, Black, Sandra E., additional, Ferrucci, Luigi, additional, Resnick, Susan M., additional, Tanaka, Toshiko, additional, Topol, Eric, additional, Torkamani, Ali, additional, Tienari, Pentti, additional, Foroud, Tatiana M., additional, Ghetti, Bernardino, additional, Landers, John E., additional, Ryten, Mina, additional, Morris, Huw R., additional, Hardy, John A., additional, Mazzini, Letizia, additional, D'Alfonso, Sandra, additional, Moglia, Cristina, additional, Calvo, Andrea, additional, Serrano, Geidy E., additional, Beach, Thomas G., additional, Ferman, Tanis, additional, Graff-Radford, Neill R., additional, Boeve, Bradley F., additional, Wszolek, Zbigniew K., additional, Dickson, Dennis W., additional, Chiò, Adriano, additional, Bennett, David A., additional, De Jager, Philip L., additional, Ross, Owen A., additional, Dalgard, Clifton L., additional, Gibbs, J. Raphael, additional, Traynor, Bryan J., additional, Scholz, Sonja W., additional, Soltis, Anthony R., additional, Viollet, Coralie, additional, Sukumar, Gauthaman, additional, Alba, Camille, additional, Lott, Nathaniel, additional, McGrath Martinez, Elisa, additional, Tuck, Meila, additional, Singh, Jatinder, additional, Bacikova, Dagmar, additional, Zhang, Xijun, additional, Hupalo, Daniel N., additional, Adeleye, Adelani, additional, Wilkerson, Matthew D., additional, Pollard, Harvey B., additional, Gan-Or, Ziv, additional, Rogaeva, Ekaterina, additional, Brice, Alexis, additional, Lesage, Suzanne, additional, Xiromerisiou, Georgia, additional, Canosa, Antonio, additional, Chio, Adriano, additional, Logroscino, Giancarlo, additional, Mora, Gabriele, additional, Krüger, Reijko, additional, May, Patrick, additional, Alcolea, Daniel, additional, Clarimon, Jordi, additional, Fortea, Juan, additional, Gonzalez-Aramburu, Isabel, additional, Infante, Jon, additional, Lage, Carmen, additional, Lleó, Alberto, additional, Pastor, Pau, additional, Sanchez-Juan, Pascual, additional, Brett, Francesca, additional, Aarsland, Dag, additional, Al-Sarraj, Safa, additional, Attems, Johannes, additional, Gentleman, Steve, additional, Hodges, Angela K., additional, Love, Seth, additional, McKeith, Ian G., additional, Morris, Christopher M., additional, Palmer, Laura, additional, Pickering-Brown, Stuart, additional, Thomas, Alan J., additional, Troakes, Claire, additional, Barrett, Matthew J., additional, Bekris, Lynn M., additional, Faber, Kelley, additional, Flanagan, Margaret E., additional, Goate, Alison, additional, Goldstein, David S., additional, Kaufmann, Horacio, additional, Kukull, Walter A., additional, Leverenz, James B., additional, Lopez, Grisel, additional, Mao, Qinwen, additional, Masliah, Eliezer, additional, Monuki, Edwin, additional, Newell, Kathy L., additional, Palma, Jose-Alberto, additional, Perkins, Matthew, additional, Renton, Alan E., additional, Scherzer, Clemens R., additional, Shakkottai, Vikram G., additional, Sidransky, Ellen, additional, Tayebi, Nahid, additional, Woltjer, Randy, additional, Baloh, Robert H., additional, Bowser, Robert, additional, Broach, James, additional, Camu, William, additional, Cooper-Knock, John, additional, Drepper, Carsten, additional, Drory, Vivian E., additional, Dunckley, Travis L., additional, Feldman, Eva, additional, Fratta, Pietro, additional, Gerhard, Glenn, additional, Gibson, Summer B., additional, Glass, Jonathan D., additional, Harms, Matthew B., additional, Heiman-Patterson, Terry D., additional, Jansson, Lilja, additional, Kirby, Janine, additional, Kwan, Justin, additional, Laaksovirta, Hannu, additional, Landi, Francesco, additional, Le Ber, Isabelle, additional, Lumbroso, Serge, additional, MacGowan, Daniel J.L., additional, Maragakis, Nicholas J., additional, Mouzat, Kevin, additional, Myllykangas, Liisa, additional, Orrell, Richard W., additional, Ostrow, Lyle W., additional, Pamphlett, Roger, additional, Pioro, Erik, additional, Pulst, Stefan M., additional, Ravits, John M., additional, Robberecht, Wim, additional, Rothstein, Jeffrey D., additional, Sendtner, Michael, additional, Shaw, Pamela J., additional, Sidle, Katie C., additional, Simmons, Zachary, additional, Stein, Thor, additional, Stone, David J., additional, Tienari, Pentti J., additional, Valori, Miko, additional, Van Damme, Philip, additional, Van Deerlin, Vivianna M., additional, Van Den Bosch, Ludo, additional, and Zinman, Lorne, additional
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- 2023
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44. N°166 – Cross-sectional axonal excitability and motor unit number index profile in early stages of weakness in ALS
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Phung, Liane, primary, Santos-Neto, Denizart, additional, Castro, Pedro, additional, Parks, Andrea, additional, Escorcio-Bezerra, Marcio, additional, Jones, Kelvin, additional, Zinman, Lorne, additional, and Abrahao, Agessandro, additional
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- 2023
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45. COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success
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Shefner, Jeremy M., primary, Al-Chalabi, Ammar, additional, Andrews, Jinsy A., additional, Chio, Adriano, additional, De Carvalho, Mamede, additional, Cockroft, Bettina M., additional, Corcia, Philippe, additional, Couratier, Philippe, additional, Cudkowicz, Merit E., additional, Genge, Angela, additional, Hardiman, Orla, additional, Heiman-Patterson, Terry, additional, Henderson, Robert D., additional, Ingre, Caroline, additional, Jackson, Carlayne E., additional, Johnston, Wendy, additional, Lechtzin, Noah, additional, Ludolph, Albert, additional, Maragakis, Nicholas J., additional, Miller, Timothy M., additional, Mora Pardina, Jesus S., additional, Petri, Susanne, additional, Simmons, Zachary, additional, Van Den Berg, Leonard H., additional, Zinman, Lorne, additional, Kupfer, Stuart, additional, Malik, Fady I., additional, Meng, Lisa, additional, Simkins, Tyrell J., additional, Wei, Jenny, additional, Wolff, Andrew A., additional, and Rudnicki, Stacy A., additional
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- 2023
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46. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS
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Miller, Timothy M, Cudkowicz, Merit E, Andrews, Jinsy A, Hesters, Adele, Kermorvant, Hugo, Lacomblez, Lucette, Forestier, Nadine Le, Lenglet, Thimotée, Retail, Maryvonne, Ruiz Del Mar Amador, Maria, Salachas, François, Shotar, Eimad, Sourour, Nader, Babu, Suma, Dorst, Johannes, Froehlich, Elke, Fromm, Andrea, Kandler, Katharina, Langer, Eva, Leichtle, Sarah, Ludolph, Albert, Mayer, Kristina, Michels, Sebastian, Raubold, Sabine, Benatar, Michael, Schuster, Joachim, Weiland, Ulrike, Wiesenfarth, Maximilian, Witzel, Simon, Calvo, Andrea, Canosa, Antonio, Casale, Federico, Chiò, Adriano, Fuda, Giuseppe, Grassano, Maurizio, McDermott, Christopher J, Marchese, Giulia, Moglia, Cristina, Palumbo, Francesca, Salamone, Paolina, Ajiki, Takahiro, Akasaka, Aya, Ando, Masahiro, Arata, Hitoshi, Asuka, Kitamura, Baba, Kosuke, Cochrane, Thos, Bekku, Goichi, Chiba, Tomoya, Date, Yugaku, Eriko, Takeuchi, Hashiguchi, Akihiro, Hatatori, Ritsuko, Hayano, Eri, Hayashi, Yuto, Higashi, Keiko, Higuchi, Eriko, Chary, Sowmya, Hiramatsu, Yu, Horikawa, Rui, Ikenaka, Kensuke, Ishiura, Hiroyuki, Ito, Daisuke, Kawai, Sachiko, Kikuchi, Junko, Kuzuyama, Haruko, Li, Xuehong, Matsumoto, Chika, Chew, Sheena, Matsuura, Eiji, Michizono, Kumiko, Mitsui, Jun, Mitsutake, Akihiko, Mochizuki, Hideki, Nagamatsu, Akemi, Nagano, Seiichi, Nakamura, Tomonori, Naruse, Hiroya, Ogasawara, Asuka, Zhu, Han, Okada, Kensuke, Okamoto, Yuji, Okuno, Tatsusada, Oyama, Satoshi, Ozono, Tatsuhiko, Sakiyama, Yusuke, Sakuishi, Kaori, Seki, Morinobu, Shibata, Shota, Shimizu, Mikito, Wu, Fan, Takahata, Katsunori, Takahito, Yoshizaki, Takashima, Hiroshi, Takeichi, Hiroko, Tashiro, Yuichi, Toda, Tatsushi, Tomizu, Yuki, Tomoya, Wadayama, Ujiakira, Nishiike, Yashita, Daiki, Nestorov, Ivan, Al-Chalabi, Ammar, Alix, James, Bangalore, Priyadarshini, Blackburn, Daniel, Chiwera, Theresa, Clegg, Rosie, Collins, Alexis, Cooper-Knock, Jonathan, Emery, Anna, Franklin, John, Genge, Angela, Graham, Danielle, Green, Louisa, Harvey, Callum, Hobson, Esther, Islam, Mahjabim, Jenkins, Thomas Michael, Kazoka, Mbombe, Kelly, Gillian, Korley, Mercy, Madarshahaian, Daniel, Mayl, Keith, Sun, Peng, McDermott, Christopher John, Radford, Alex, Shaw, Christopher, Shaw, Pamela J, Sidebottom, Joe, Smart, Lynne, Sreedharan, Jemeen, Stone, Ben, Tsironis, Theocharis, Tuddenham, Lee, McNeill, Manjit, Verber, Nick, Wollff, Helen, Young, Stacy, Zis, Panagiotis, Adamo, Ashley, Ahmed, Arubah, Ajroud-Driss, Senda, Alameda, Gustave, Arcila-Londono, Ximena, Fanning, Laura, Baird, Candy, Bazan, Tracy, Berry, James, Bordeau, Jane, Bradford, Wendy, Brook, Nyda, Brown, Lauren, Bucelli, Robert C, Ferguson, Toby A, Buckner, Katherine, Budler, Michael W, Burba, Lindita, Burke, Katherine, Calhoun, Ashley D, Campbell, Sarah, Carey, Judith, Caristo, Irys B, Carty, Simon, Chan, Emmanuel, Fradette, Stephanie, Chaudhry, Vinay, Chen, Ricky, Chow, Saephanh, Clawson, Lora L, Clemens, Mitchell, Cloninger, Suzann E, Coleman-Wood, Krista, Cooper, Thomas N, Cummings, Arlena, Daniels, Jacquelyn, VALOR, DeSaro, Pamela, DeWitt, Michelle, Dedi, Brixhilda, Dempsey, Debbie, Denny, Carol, Doherty, Jenna, Doherty, Leana, Donahue, Megan, Doyle, Michael, Duncan, Jessie, Group, OLE Working, Elman, Lauren, Eloge, Christine M, Echiti, Desirae R, Ferrey, Dominic, Fournier, Christina, Fukumura, Yuriko, Gallagher, Katherine, Garaycoa, Jessica, Garrett, Mark, Gibson, Richard L, Beullens, Lien, Gifford, Ryan, Glass, Jonathan D, Gogol, Danuta, Golden, Shea, Gonzalez, Alexa, Goodman, Ira, Goolsby, Christopher, Goslin, Kimberly, Goulbourne, Michael, Granit, Volkan, Claeys, Kristl, Grignon, Anne-Laure, GuhaRay, Adreeja, Guide, Debra, Gundogdu, Melek Betul, Gutierrez, Gil, Hastings, Debbie, Hayzen, Colleen, Herzog, Hilary, Holloway, Raegan, Jacobs, Gabriel, Claeys, Thomas, Jacobsen, Bill, James, Virginia, Jenkins, Liberty, Jockel-Balsarotti, Jennifer, Johnson, Linda Carol, Jose, Sunil, Joslin, Benjamin, Karanja, Elizabeth, Katz, Jonathan, Keener, Anthony, Couwelier, Goedele, Kittle, Gale, Klein, Sara, Kreple, Collin, Rebecca, Rebecca, Kuenzler, Kuenzler, Kusnir, Jorge, Labbe, Kristen, Lachica-Encinas, Nicolet, Ladha, Shafeeq, Leimer, Lesli, D'Hondt, Ann, Levy, Michael, Levy, Wendy, Li, Yingji, Likanje, Marie-France, Livigni, Rebecca, Locatelli, Eduardo, Luppino, Sarah, Malcolm, Amber, Maragakis, Nicholas, Marin, Horia, Debien, Elisa, Markowitz, Clyde, Markway, Jesse, McCaffrey, Alexandra, McCoy, Arita, McCoy Gross, Kelly, Mehta, Kush, Meyer, Robert, Milan, Jennifer, Miller, Timothy, Miller, Robert G, de Keersmaecker, Sebastiaan, Morales, Francisco, Mosmiller, Elizabeth, Mott, Donovan, Moulton, Kelsey, Murphy, Christine A, Negron, Tirso, Nelson, Cassandra, Newman, Daniel S, Nissinen, Janne Kristoffer, Norman, Andrew, Della Faille, Laetitia, Ohkubo, Takuya, Olney, Nicholas, Ortiz, Natasha, Oskarsson, Bjorn, Pace, Mitchell, Packard, Kathleen, Padgett, Denny, Paganoni, Sabrina, Paredes, Maria E, Parker, Elizabeth, Delmotte, Koen, Partlow, Ann, Pattee, Gary L, Paulett, Jany, Pelot, Antoinette, Pfeifer, Kyle M, Pijanowski, Olivia, Pioro, Erik, Polak, Meraida, Prakash, Ahalya, Previte, Rosemarie, Depoortere, Sofie, Pukenas, Bryan, Quinn, Colin, Ravits, John, Razavi, Ryan, Regan, Tyler, Riley, Kristen M, Roth, Heather, Sanders, Danica, Scalia, Jennifer, Schmidt, Emma, de Velder, Laura, Schwen, Edward, Shah, Jaimin, Shah, Stuti, Shefner, Jeremy, Sheldon, Danielle, Simmons, Karon, Singh, Navneet K, Singleton, Jessica, Smiley, Richard, Smith, William B, Dobbels, Laurens, Smith, Sean, Sotirchos, Elias, Sorenson, Eric, Staff, Nathan, Steele, Julie, Steijlen, Kara, Stirrat, Taylor, Stoica, George S, Strong, Stephanie, Sufit, Robert, Sobue, Gen, Gijs, Jeroen, Sultze, Jane, Swartz, Amy, Szymanski, April, Tay, Anna, Thakore, Nimish, Thiessen, Diana, Thotala, Sukrutha, Trudell, Randall G, Turcotte, Nicole, Turner, Michelle, Horckmans, Simon, Uchil, Alpa, Upadhyay, Vihar, Usman, Uzma, Vallis, Anne, Vaporean-Bussey, Danielle, Vladimirova, Valentine, Weber, Harli, Winbigler, Jennifer, Wojanowski, Heather, Wulf, Charlie, Lamaire, Nikita, Yasek, Julia, Yoo, Stephanie, Zivalic, Hannah, Cole, Alexandra, File, Greta, Foate, Jeremy, Mason, Deborah, Newton, Susan, Roberts, Stephen, Sellwood, Cory Dean, Liessens, Hannelore, Swan, James, Werno, Anja, Zhong, Cathy, Masrori, Pegah, Nysten, Celine, Schotte, Caroline, Serrien, Anouk, Swinnen, Bart, Tilkin, Petra, van Daele, Sien, Van Damme, Philip, Vynckier, Jan, Wouters, Anke, Abrahao, Agessandro, Angle, Mark, Badawy, Mohamed, Berube, Maxime, Bertone, Vanessa, Cooper, Sarah Marie, Dobrowolski, Peter, Fong, Helen, Hannouche, Matthew, Hartley, Denise, Hogan, Michael, Johnston, Wendy, Khalfallah, Yousra, Korngut, Lawrence, Kroetsch, Gina, Letourneau, Justin, Magnussen, Claire, Martinez, Jose, Massie, Rami, Mobach, Theodore, Mookshah, Jahan, Ozelsel, Timur, Parks, Andrea, Petrillo, Janet, Pfeffer, Gerald, Ludolph, Albert C, Pham, Shirley, Phung, Liane, Shiungsun, Rodney, Pi-Shan, Li, Santos, Denizart, Salmon, Kristiana, Saunders, Natalie, Sembinelli, Dylan, Tymkow, Kelsey, Wong, Berchman, Zinman, Lorne, Karlsborg, Merete, Pedersen Lomholt, Therese, Nilsson, Sigrid, Salvesen, Lisette, Skov, Pernille, Svenstrup, Kristen, Bruneteau, Gaelle, Calerencon, Frederic, and Guimaraes Costa, Raquel
- Subjects
Adult ,drug effects [Recovery of Function] ,Spinal ,Oligonucleotides ,blood [Neurofilament Proteins] ,administration & dosage [Oligonucleotides, Antisense] ,tofersen ,Injections ,blood [Amyotrophic Lateral Sclerosis] ,pharmacology [Oligonucleotides, Antisense] ,Superoxide Dismutase-1 ,Double-Blind Method ,Neurofilament Proteins ,Humans ,ddc:610 ,Antisense ,Injections, Spinal ,Biomarkers ,Recovery of Function ,Amyotrophic Lateral Sclerosis ,Oligonucleotides, Antisense ,blood [Biomarkers] ,drug therapy [Amyotrophic Lateral Sclerosis] ,therapeutic use [Oligonucleotides, Antisense] ,SOD1 protein, human ,General Medicine ,genetics [Superoxide Dismutase-1] ,genetics [Amyotrophic Lateral Sclerosis] ,cerebrospinal fluid [Biomarkers] ,cerebrospinal fluid [Superoxide Dismutase-1] ,cerebrospinal fluid [Amyotrophic Lateral Sclerosis] - Abstract
The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).
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- 2022
47. Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses
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Dilliott, Allison A., Sunderland, Kelly M., McLaughlin, Paula M., Roberts, Angela C., Evans, Emily C., Abrahao, Agessandro, Binns, Malcolm A., Black, Sandra E., Borrie, Michael, Casaubon, Leanne.K., Dowlatshahi, Dar, Finger, Elizabeth, Fischer, Corinne.E., Frank, Andrew, Freedman, Morris, Grimes, David, Hassan, Ayman, Jog, Mandar, Kumar, Sanjeev, Kwan, Donna, Lang, Anthony E., Mandzia, Jennifer, Marras, Connie, Masellis, Mario, McIntyre, Adam D., Pasternak, Stephen, Pollock, Bruce G., Rajji, Tarek K., Robinson, John F., Rogaeva, Ekaterina, Sahlas, Demetrios J., Saposnik, Gustavo, Sato, Christine, Seitz, Dallas, Shoesmith, Christen, Steeves, Thomas, Strother, Stephen C., Swartz, Richard H., Tan, Brian, Tang-Wai, David, Tartaglia, Maria C., Troyer, Angela K., Turnbull, John, Zinman, Lorne, and Hegele, Robert A.
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- 2021
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48. Speech Movement Measures as Markers of Bulbar Disease in Amyotrophic Lateral Sclerosis
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Shellikeri, Sanjana, Green, Jordan R., Kulkarni, Madhura, Rong, Panying, Martino, Rosemary, Zinman, Lorne, and Yunusova, Yana
- Abstract
Purpose: The goal of this study was to identify the effects of amyotrophic lateral sclerosis (ALS) on tongue and jaw control, both cross-sectionally and longitudinally. The data were examined in the context of their utility as a diagnostic marker of bulbar disease. Method: Tongue and jaw movements were recorded cross-sectionally (n = 33 individuals with ALS, 13 controls) and longitudinally (n = 10 individuals with ALS) using a three-dimensional electromagnetic articulography system during the production of the sentence "Buy Bobby a puppy." The movements were examined for evidence of changes in size, speed, and duration and with respect to disease severity and time in the study. Results: Maximum speed of tongue movements and movement durations were significantly different only at an advanced stage of bulbar ALS compared with the healthy control group. The longitudinal analysis revealed a reduction in tongue movement size and speed with time at early stages of disease, which was not seen cross-sectionally. As speaking rate declined, tongue movements decreased in maximum speed, whereas jaw movements increased in maximum speed. Conclusions: Longitudinal analyses of sentence-level kinematic data show their sensitivity to early bulbar impairment. A change in articulatory kinematics can serve as a useful diagnostic marker for bulbar ALS and to track bulbar disease progression in a clinical setting.
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- 2016
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49. A prospective harmonized multicenter DTI study of cerebral white matter degeneration in ALS
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Kalra, Sanjay, Müller, Hans-Peter, Ishaque, Abdullah, Zinman, Lorne, Korngut, Lawrence, Genge, Angela, Beaulieu, Christian, Frayne, Richard, Graham, Simon J., and Kassubek, Jan
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- 2020
- Full Text
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50. Rare neurovascular genetic and imaging markers across neurodegenerative diseases
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Dilliott, Allison A, Berberian, Stephanie A, Sunderland, Kelly M, Binns, Malcolm A, Zimmer, Julia, Ozzoude, Miracle, Scott, Christopher J M, Gao, Fuqiang, Lang, Anthony E, Breen, David P, Tartaglia, Maria C, Tan, Brian, Swartz, Richard H, Rogaeva, Ekaterina, Borrie, Michael, Finger, Elizabeth, Fischer, Corinne E, Frank, Andrew, Freedman, Morris, Kumar, Sanjeev, Pasternak, Stephen, Pollock, Bruce G, Rajji, Tarek K, Tang-Wai, David F, Abrahao, Agessandro, Turnbull, John, Zinman, Lorne, Casaubon, Leanne, Dowlatshahi, Dar, Hassan, Ayman, Mandzia, Jennifer, Sahlas, Demetrios, Saposnik, Gustavo, Grimes, David, Marras, Connie, Steeves, Thomas, Masellis, Mario, Farhan, Sali M K, Bartha, Robert, Symons, Sean, Hegele, Robert A, Black, Sandra E, and Ramirez, Joel
- Abstract
INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood.DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.
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- 2023
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