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144 results on '"Tartaglia, Maria C."'

1. Identifying latent disease factors differently expressed in patient subgroups using group factor analysis

Author

Ferreira, Fabio S., Ashburner, John, Bouzigues, Arabella, Suksasilp, Chatrin, Russell, Lucy L., Foster, Phoebe H., Ferry-Bolder, Eve, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Vandenberghe, Rik, de Mendonca, Alexandre, Tiraboschi, Pietro, Santana, Isabel, Gerhard, Alexander, Levin, Johannes, Sorbi, Sandro, Otto, Markus, Pasquier, Florence, Ducharme, Simon, Butler, Chris R., Ber, Isabelle Le, Finger, Elizabeth, Tartaglia, Maria C., Masellis, Mario, Rowe, James B., Synofzik, Matthis, Moreno, Fermin, Borroni, Barbara, Kaski, Samuel, Rohrer, Jonathan D., and Mourao-Miranda, Janaina

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

In this study, we propose a novel approach to uncover subgroup-specific and subgroup-common latent factors addressing the challenges posed by the heterogeneity of neurological and mental disorders, which hinder disease understanding, treatment development, and outcome prediction. The proposed approach, sparse Group Factor Analysis (GFA) with regularised horseshoe priors, was implemented with probabilistic programming and can uncover associations (or latent factors) among multiple data modalities differentially expressed in sample subgroups. Synthetic data experiments showed the robustness of our sparse GFA by correctly inferring latent factors and model parameters. When applied to the Genetic Frontotemporal Dementia Initiative (GENFI) dataset, which comprises patients with frontotemporal dementia (FTD) with genetically defined subgroups, the sparse GFA identified latent disease factors differentially expressed across the subgroups, distinguishing between "subgroup-specific" latent factors within homogeneous groups and "subgroup common" latent factors shared across subgroups. The latent disease factors captured associations between brain structure and non-imaging variables (i.e., questionnaires assessing behaviour and disease severity) across the different genetic subgroups, offering insights into disease profiles. Importantly, two latent factors were more pronounced in the two more homogeneous FTD patient subgroups (progranulin (GRN) and microtubule-associated protein tau (MAPT) mutation), showcasing the method's ability to reveal subgroup-specific characteristics. These findings underscore the potential of sparse GFA for integrating multiple data modalities and identifying interpretable latent disease factors that can improve the characterization and stratification of patients with neurological and mental health disorders., Comment: 38 pages, 14 figures

Published
2024

2. History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment

Author

Khoury, Marc A., Churchill, Nathan W., Di Battista, Alex, Graham, Simon J., Symons, Sean, Troyer, Angela K., Roberts, Angela, Kumar, Sanjeev, Tan, Brian, Arnott, Stephen R., Ramirez, Joel, Tartaglia, Maria C., Borrie, Michael, Pollock, Bruce, Rajji, Tarek K., Pasternak, Stephen H., Frank, Andrew, Tang-Wai, David F., Scott, Christopher J. M., Haddad, Seyyed Mohammad Hassan, Nanayakkara, Nuwan, Orange, Joseph B., Peltsch, Alicia, Fischer, Corinne E., Munoz, David G., and Schweizer, Tom A.

Published
2024
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3. Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions

Author

Garcia-Cordero, Indira, Vasilevskaya, Anna, Taghdiri, Foad, Khodadadi, Mozhgan, Mikulis, David, Tarazi, Apameh, Mushtaque, Asma, Anssari, Neda, Colella, Brenda, Green, Robin, Rogaeva, Ekaterina, Sato, Christine, Grinberg, Mark, Moreno, Danielle, Hussain, Mohammed W., Blennow, Kaj, Zetterberg, Henrik, Davis, Karen D., Wennberg, Richard, Tator, Charles, and Tartaglia, Maria C.

Published
2024
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4. Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration

Author

Rojas, Julio C, Wang, Ping, Staffaroni, Adam M, Heller, Carolin, Cobigo, Yann, Wolf, Amy, Goh, Sheng-Yang M, Ljubenkov, Peter A, Heuer, Hilary W, Fong, Jamie C, Taylor, Joanne B, Veras, Eliseo, Song, Linan, Jeromin, Andreas, Hanlon, David, Yu, Lili, Khinikar, Arvind, Sivasankaran, Rajeev, Kieloch, Agnieszka, Valentin, Marie-Anne, Karydas, Anna M, Mitic, Laura L, Pearlman, Rodney, Kornak, John, Kramer, Joel H, Miller, Bruce L, Kantarci, Kejal, Knopman, David S, Graff-Radford, Neill, Petrucelli, Leonard, Rademakers, Rosa, Irwin, David J, Grossman, Murray, Ramos, Eliana Marisa, Coppola, Giovanni, Mendez, Mario F, Bordelon, Yvette, Dickerson, Bradford C, Ghoshal, Nupur, Huey, Edward D, Mackenzie, Ian R, Appleby, Brian S, Domoto-Reilly, Kimiko, Hsiung, Ging-Yuek R, Toga, Arthur W, Weintraub, Sandra, Kaufer, Daniel I, Kerwin, Diana, Litvan, Irene, Onyike, Chiadikaobi U, Pantelyat, Alexander, Roberson, Erik D, Tartaglia, Maria C, Foroud, Tatiana, Chen, Weiping, Czerkowicz, Julie, Graham, Danielle L, van Swieten, John C, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R, Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Cash, David M, Convery, Rhian S, Bocchetta, Martina, Foiani, Martha, Greaves, Caroline V, Peakman, Georgia, Russell, Lucy, Swift, Imogen, Todd, Emily, Rohrer, Jonathan D, Boeve, Bradley F, Rosen, Howard J, Boxer, Adam L, and consortia, on behalf of the ALLFTD and GENFI

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurodegenerative, Genetics, Prevention, Dementia, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Alzheimer's Disease, Frontotemporal Dementia (FTD), Aging, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Disease Progression, Female, Frontotemporal Lobar Degeneration, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurofilament Proteins, Predictive Value of Tests, Young Adult, ALLFTD and GENFI consortia, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression.MethodsBaseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables.ResultsIn both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers.ConclusionsPlasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials.Trial registration informationClinicalTrials.gov Identifier: NCT02372773 and NCT02365922.Classification of evidenceThis study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression.

Published
2021

5. Utility of the global CDR® plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium

Author

Miyagawa, Toji, Brushaber, Danielle, Syrjanen, Jeremy, Kremers, Walter, Fields, Julie, Forsberg, Leah K, Heuer, Hilary W, Knopman, David, Kornak, John, Boxer, Adam, Rosen, Howard J, Boeve, Bradley F, Appleby, Brian, Bordelon, Yvette, Bove, Jessica, Brannelly, Patrick, Caso, Christina, Coppola, Giovanni, Dever, Reilly, Dheel, Christina, Dickerson, Bradford, Dickinson, Susan, Dominguez, Sophia, Domoto‐Reilly, Kimiko, Faber, Kelley, Ferrell, Jessica, Fishman, Ann, Fong, Jamie, Foroud, Tatiana, Gavrilova, Ralitza, Gearhart, Debra, Ghazanfari, Behnaz, Ghoshal, Nupur, Goldman, Jill S, Graff‐Radford, Jonathan, Graff‐Radford, Neill, Grant, Ian, Grossman, Murray, Haley, Dana, Hsiung, Robin, Huey, Edward, Irwin, David, Jones, David, Jones, Lynne, Kantarci, Kejal, Karydas, Anna, Kaufer, Daniel, Kerwin, Diana, Kraft, Ruth, Kramer, Joel, Kukull, Walter, Litvan, Irene, Lucente, Diane, Lungu, Codrin, Mackenzie, Ian, Maldonado, Miranda, Manoochehri, Masood, McGinnis, Scott, McKinley, Emily, Mendez, Mario F, Miller, Bruce, Multani, Namita, Onyike, Chiadi, Padmanabhan, Jaya, Pantelyat, Alexander, Pearlman, Rodney, Petrucelli, Leonard, Potter, Madeline, Rademakers, Rosa, Ramos, Eliana M, Rankin, Kate, Rascovsky, Katya, Roberson, Erik D, Rogalski, Emily, Sengdy, Pheth, Shaw, Leslie, Tartaglia, Maria C, Tatton, Nadine, Taylor, Joanne, Toga, Arthur, Trojanowski, John Q, Wang, Ping, Weintraub, Sandra, Wong, Bonnie, and Wszolek, Zbigniew

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Dementia, Frontotemporal Dementia (FTD), Neurosciences, Neurodegenerative, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Brain Disorders, Aged, Aphasia, Primary Progressive, Cross-Sectional Studies, Female, Frontotemporal Lobar Degeneration, Humans, Male, Mental Status and Dementia Tests, Middle Aged, behavior, comportment, personality, CDR, CDR plus NACC FTLD, frontotemporal lobar degeneration, global rating, language, CDR®, behavior, comportment, and personality, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWe created global rating scoring rules for the CDR® plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.MethodsThe CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score. An interrater reliability study was completed for 40 participants.ResultsThe CDR plus NACC FTLD showed very good interrater reliability. It was especially useful in detecting clinical features of mild non-fluent/agrammatic variant primary progressive aphasia participants.DiscussionThe global CDR plus NACC FTLD score could be an attractive outcome measure for clinical trials in symptomatic FTLD, and may be useful in natural history studies and clinical trials in FTLD spectrum disorders.

Published
2020

6. Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

Author

Brittain, Claire, McCarthy, Andrew, Irizarry, Michael C, McDermott, Dana, Biglan, Kevin, Höglinger, Günter U, Lorenzl, Stefan, del Ser, Teodoro, Boxer, Adam L, Group, The AL-108-231 Study, Williams, David, Lafontaine, Anne Louise, Marras, Connie, Jog, Mandar, Panisset, Michael, Lang, Anthony, Parker, Lesley, Stewart, Alistair J, Corvol, Jean-Christophe, Azulay, Jean-Philippe, Couratier, Philippe, Mollenhauer, Brit, Ludolph, Albert, Benecke, Reiner, Hoglinger, Gunter, Lipp, Axel, Reichmann, Heinz, Woitalla, Dirk, Chan, Dennis, Zermansky, Adam, Burn, David, Lees, Andrew, Gozes, Illana, Boxer, Adam, Miller, Bruce L, Lobach, Iryna V, Roberson, Erik, Honig, Lawrence, Zamrini, Edward, Pahwa, Rajesh, Bordelon, Yvette, Driver-Dunkley, Erika, Lessig, Stephanie, Lew, Mark, Womack, Kyle, Boeve, Brad, Ferrara, Joseph, Hillis, Argyle, Kaufer, Daniel, Kumar, Rajeev, Xie, Tao, Gunzler, Steven, Zesiewicz, Theresa, Dayalu, Praveen, Golbe, Lawrence, Grossman, Murray, Jankovic, Joseph, McGinnis, Scott, Santiago, Anthony, Tuite, Paul, Isaacson, Stuart, Leegwater-Kim, Julie, Litvan, Irene, Knopman, David S, Schneider, Lon S, Doody, Rachelle S, Golbe, Lawrence I, Roberson, Erik D, Koestler, Mary, Jack, Clifford R, Van Deerlin, Viviana, Randolph, Christopher, Whitaker, Steve, Hirman, Joe, Gold, Michael, Morimoto, Bruce H, investigators, The PROPSPERA, G, Georg Nuebling, Hensler, Mira, Paul, Sabine, Zwergal, Andreas, 4RNTI-1authors, Heuer, Hilary W, Tartaglia, Maria C, McGinnis, Scott M, Dickerson, Bradford C, Kornak, John, Schuff, Norbert, Rabinovici, Gil D, Rosen, Howard J, Investigators, Tau Restoration on PSP, Gómez, JC, Tijero, B, Berganzo, K, de Yebenes, J Garc'ıa, Sendón, JL Lopez, and Garcia, G

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Frontotemporal Dementia (FTD), Clinical Research, Aging, Alzheimer's Disease Related Dementias (ADRD), Health Disparities, Clinical Trials and Supportive Activities, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Rare Diseases, Dementia, 4.2 Evaluation of markers and technologies, Neurological, Aged, Aged, 80 and over, Basal Ganglia Diseases, Data Visualization, Disease Progression, Female, Humans, Male, Middle Aged, Models, Neurological, Neurodegenerative Diseases, Prognosis, Severity of Illness Index, Supranuclear Palsy, Progressive, Syndrome, Corticobasal syndrome, Progressive supranuclear palsy, PSP rating scale, Interactive visualizations, Predictive models, AL-108-231 Study Group, PROPSPERA investigators, 4RNTI-1authors, Tau Restoration on PSP (TAUROS) Investigators, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundProgressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP.ObjectivesTo determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS.MethodsMulticenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity.ResultsThe earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity.ConclusionThe PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

Published
2019

8. Epileptic activity in Alzheimer's disease: causes and clinical relevance

Author

Vossel, Keith A, Tartaglia, Maria C, Nygaard, Haakon B, Zeman, Adam Z, and Miller, Bruce L

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Aging, Epilepsy, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Animals, Anticonvulsants, Humans, Neurology & Neurosurgery, Clinical sciences
Abstract

Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer's disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer's disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.

Published
2017

9. Progression of brain atrophy in PSP and CBS over 6 months and 1 year

Author

Dutt, Shubir, Binney, Richard J, Heuer, Hilary W, Luong, Phi, Attygalle, Suneth, Bhatt, Priyanka, Marx, Gabe A, Elofson, Jonathan, Tartaglia, Maria C, Litvan, Irene, McGinnis, Scott M, Dickerson, Bradford C, Kornak, John, Waltzman, Dana, Voltarelli, Lisa, Schuff, Norbert, Rabinovici, Gil D, Kramer, Joel H, Jack, Clifford R, Miller, Bruce L, Rosen, Howard J, Boxer, Adam L, Williams, David, Lafontaine, Anne Louise, Marras, Connie, Jog, Mandar, Panisset, Michael, Lang, Anthony, Parker, Lesley, Stewart, Alistair J, Corvol, Jean-Christophe, Azulay, Jean-Philippe, Couratier, Philippe, Mollenhauer, Brit, Lorenzl, Stefan, Ludolph, Albert, Benecke, Reiner, Hoglinger, Gunter, Lipp, Axel, Reichmann, Heinz, Woitalla, Dirk, Chan, Dennis, Zermansky, Adam, Burn, David, Lees, Andrew, Gozes, Illana, Boxer, Adam, Lobach, Iryna V, Roberson, Erik, Honig, Lawrence, Zamrini, Edward, Pahwa, Rajesh, Bordelon, Yvette, Driver-Dunkley, Erika, Lessig, Stephanie, Lew, Mark, Womack, Kyle, Boeve, Brad, Ferrara, Joseph, Hillis, Argyle, Kaufer, Daniel, Kumar, Rajeev, Xie, Tao, Gunzler, Steven, Zesiewicz, Theresa, Dayalu, Praveen, Golbe, Lawrence, Grossman, Murray, Jankovic, Joseph, McGinnis, Scott, Santiago, Anthony, Tuite, Paul, Isaacson, Stuart, Leegwater-Kim, Julie, Knopman, David S, Schneider, Lon S, Doody, Rachelle S, Koestler, Mary, Van Deerlin, Viviana, Randolph, Christopher, Whitaker, Steve, Hirman, Joe, Gold, Michael, Morimoto, and , Bruce H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Aging, Rare Diseases, Alzheimer's Disease, Clinical Research, Neurosciences, Brain Disorders, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Atrophy, Basal Ganglia, Cerebral Cortex, Disease Progression, Female, Follow-Up Studies, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Statistics, Nonparametric, Supranuclear Palsy, Progressive, AL-108-231 investigators, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents.MethodsSix- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial.ResultsPatients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale.ConclusionsVolume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.

Published
2016

10. Oxytocin for frontotemporal dementia

Author

Finger, Elizabeth C, MacKinley, Julia, Blair, Mervin, Oliver, Lindsay D, Jesso, Sarah, Tartaglia, Maria C, Borrie, Michael, Wells, Jennie, Dziobek, Isabel, Pasternak, Stephen, Mitchell, Derek GV, Rankin, Katherine, Kertesz, Andrew, and Boxer, Adam

Subjects
Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Rare Diseases, Dementia, Brain Disorders, Aging, Neurodegenerative, Clinical Research, Frontotemporal Dementia (FTD), Neurosciences, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Neurological, Administration, Intranasal, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Double-Blind Method, Emotions, Empathy, Female, Frontotemporal Dementia, Humans, Male, Middle Aged, Oxytocin, Treatment Outcome, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD).MethodsWe conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects.ResultsAll 3 doses of intranasal oxytocin were safe and well tolerated.ConclusionsA multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD.Classification of evidenceThis study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.

Published
2015

11. Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

Author

Williams, David, Lafontaine, Anne Louise, Marras, Connie, Jog, Mandar, Panisset, Michael, Lang, Anthony, Parker, Lesley, Stewart, Alistair J., Corvol, Jean-Christophe, Azulay, Jean-Philippe, Couratier, Philippe, Mollenhauer, Brit, Lorenzl, Stefan, Ludolph, Albert, Benecke, Reiner, Hoglinger, Gunter, Lipp, Axel, Reichmann, Heinz, Woitalla, Dirk, Chan, Dennis, Zermansky, Adam, Burn, David, Lees, Andrew, Gozes, Illana, Boxer, Adam, Miller, Bruce L., Lobach, Iryna V., Roberson, Erik, Honig, Lawrence, Zamrini, Edward, Pahwa, Rajesh, Bordelon, Yvette, Driver-Dunkley, Erika, Lessig, Stephanie, Lew, Mark, Womack, Kyle, Boeve, Brad, Ferrara, Joseph, Hillis, Argyle, Kaufer, Daniel, Kumar, Rajeev, Xie, Tao, Gunzler, Steven, Zesiewicz, Theresa, Dayalu, Praveen, Golbe, Lawrence, Grossman, Murray, Jankovic, Joseph, McGinnis, Scott, Santiago, Anthony, Tuite, Paul, Isaacson, Stuart, Leegwater-Kim, Julie, Litvan, Irene, Knopman, David S., Schneider, Lon S., Doody, Rachelle S., Golbe, Lawrence I., Roberson, Erik D., Koestler, Mary, Jack, Clifford R., Jr., Van Deerlin, Viviana, Randolph, Christopher, Whitaker, Steve, Hirman, Joe, Gold, Michael, Morimoto, Bruce H., Nuebling G, Georg, Hensler, Mira, Paul, Sabine, Zwergal, Andreas, Heuer, Hilary W., Tartaglia, Maria C., McGinnis, Scott M., Dickerson, Bradford C., Kornak, John, Schuff, Norbert, Rabinovici, Gil D., Rosen, Howard J., Boxer, Adam L., Gómez, J.C., Tijero, B., Berganzo, K., Garc'ıa de Yebenes, J., Lopez Sendón, J.L., Garcia, G., Tolosa, E., Buongiorno, M.T., Bargalló, N., Burguera, J.A., Martinez, I., Ruiz-Mart'ınez, J., Narrativel, I., Vivancos, F., Ybot, I., Aguilar, M., Quilez, P., Boada, M., Lafuente, A., Hernandez, I., López-Lozano, J.J., Mata, M., Kupsch, A., Lipp, A., Ebersbach, G., Schmidt, T., Hahn, K., Höglinger, G., Höllerhage, M., Oertel, W.H., Respondek, G., Stamelou, M., Reichmann, H., Wolz, M., Schneider, C., Klingelhöfer, L., Berg, D., Maetzler, W., Srulijes, K.K., Ludolph, A., Kassubek, J., Steiger, M., Tyler, K., Burn, D.J., Morris, L., Lees, A., Ling, H., Hauser, R., McClain, T., Truong, D., Jenkins, S., Litvan, I., Houghton, D., Ferrara, J., Bordelon, Y., Gratiano, A., Golbe, L., Mark, M., Uitti, R., Ven Gerpen, J., Brittain, Claire, McCarthy, Andrew, Irizarry, Michael C., McDermott, Dana, Biglan, Kevin, Höglinger, Günter U., and del Ser, Teodoro

Published
2019
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12. Use of the CDR® plus NACC FTLD in mild FTLD: Data from the ARTFL/LEFFTDS consortium

Author

Appleby, Brian, Bordelon, Yvette, Bove, Jessica, Brannelly, Patrick, Caso, Christina, Coppola, Giovanni, Dever, Reilly, Dheel, Christina, Dickerson, Bradford, Dickinson, Susan, Dominguez, Sophia, Domoto-Reilly, Kimiko, Faber, Kelley, Ferrell, Jessica, Fishman, Ann, Fong, Jamie, Foroud, Tatiana, Gavrilova, Ralitza, Gearhart, Debra, Ghazanfari, Behnaz, Ghoshal, Nupur, Goldman, Jill S., Graff-Radford, Jonathan, Graff-Radford, Neill, Grant, Ian, Grossman, Murray, Haley, Dana, Hsiung, Robin, Huey, Edward, Irwin, David, Jones, David, Jones, Lynne, Kantarci, Kejal, Karydas, Anna, Kaufer, Daniel, Kerwin, Diana, Kraft, Ruth, Kramer, Joel, Kukull, Walter, Litvan, Irene, Lucente, Diane, Lungu, Codrin, Mackenzie, Ian, Maldonado, Miranda, Manoochehri, Masood, McGinnis, Scott, McKinley, Emily, Mendez, Mario F., Miller, Bruce, Multani, Namita, Onyike, Chiadi, Padmanabhan, Jaya, Pantelyat, Alexander, Pearlman, Rodney, Petrucelli, Leonard, Potter, Madeline, Rademakers, Rosa, Ramos, Eliana M., Rankin, Kate, Rascovsky, Katya, Roberson, Erik D., Rogalski, Emily, Sengdy, Pheth, Shaw, Leslie, Tartaglia, Maria C., Tatton, Nadine, Taylor, Joanne, Toga, Arthur, Trojanowski, John Q., Wang, Ping, Weintraub, Sandra, Wong, Bonnie, Wszolek, Zbigniew, Miyagawa, Toji, Brushaber, Danielle, Syrjanen, Jeremy, Kremers, Walter, Fields, Julie, Forsberg, Leah K., Heuer, Hilary W., Knopman, David, Kornak, John, Boxer, Adam, Rosen, Howie, and Boeve, Bradley

Published
2019
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13. Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

Author

Rashidi‐Ranjbar, Neda, Churchill, Nathan W., Black, Sandra E., Kumar, Sanjeev, Tartaglia, Maria C., Freedman, Morris, Lang, Anthony, Steeves, Thomas D. L., Swartz, Richard H., Saposnik, Gustavo, Sahlas, Dametrios, McLaughlin, Paula, Symons, Sean, Strother, Stephen, Pollock, Bruce G., Rajji, Tarek K., Ozzoude, Miracle, Tan, Brian, Arnott, Stephen R., and Bartha, Robert

Subjects
DEMENTIA risk factors, BRAIN anatomy, RISK assessment, BEHAVIOR disorders, CROSS-sectional method, STATISTICAL correlation, MILD cognitive impairment, RESEARCH funding, BRAIN, NEURAL pathways, QUESTIONNAIRES, EXECUTIVE function, PARKINSON'S disease, SEVERITY of illness index, APPETITE, AGITATION (Psychology), DESCRIPTIVE statistics, LONGITUDINAL method, RESEARCH, FRONTAL lobe, LIMBIC system, DEMENTIA, CEREBROVASCULAR disease, BRAIN cortical thickness, APATHY, TIME, SYMPTOMS
Abstract

Objectives: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross‐sectionally and longitudinally across various neurodegenerative diagnoses. Methods: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2‐years follow‐up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal‐executive circuits. Results: Cross‐sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal‐executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal‐executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal‐executive circuits, respectively. Conclusions: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross‐sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences. Key points: What is the primary question addressed by this study? The structural neural correlates of neuropsychiatric symptoms (NPS) in multiple neurodegenerative diagnoses. What is the main finding of this study? Our study reveals the involvement of both corticolimbic and frontal‐executive circuits in three populations at risk for developing dementia, with these circuits showing significant associations with NPS. The distinct neural correlates were observed within each population, shedding light on the neurobiological mechanisms underlying NPS in these disorders and providing a better understanding of their progression toward dementia. What is the meaning of the finding? These results have significant implications for the early detection and management of NPS in patients with neurodegenerative disorders and may inform the development of more effective treatment strategies in the future. Furthermore, the difference between cross‐sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Neurodegenerative Disease Phenotypes in Carriers of MAPT p.A152T, A Risk Factor for Frontotemporal Dementia Spectrum Disorders and Alzheimer Disease

Author

Lee, Suzee E, Tartaglia, Maria C, Yener, Görsev, Genç, Sermin, Seeley, William W, Sanchez-Juan, Pascual, Moreno, Fermin, Mendez, Mario F, Klein, Eric, Rademakers, Rosa, de Munain, Adolfo López, Combarros, Onofre, Kramer, Joel H, Kenet, Robert O, Boxer, Adam L, Geschwind, Michael D, Gorno-Tempini, Maria-Luisa, Karydas, Anna M, Rabinovici, Gil D, Coppola, Giovanni, Geschwind, Daniel H, and Miller, Bruce L

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), Dementia, Aging, Genetics, Brain Disorders, Alzheimer's Disease, Rare Diseases, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Female, Frontotemporal Dementia, Genetic Variation, Heterozygote, Humans, Male, Middle Aged, Neurodegenerative Diseases, Phenotype, Retrospective Studies, Risk Factors, tau Proteins, all cognitive disorders, dementia, Alzheimer disease, frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, Cognitive Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

Published
2013

15. MICROSTRUCTURAL CHANGES IN THE PENUMBRAS OF CEREBRAL SMALL VESSEL DISEASE LESIONS ARE ASSOCIATED WITH COGNITION AND SLEEP

Author

Ramirez, Joel, Walker, Kirstin, McSweeney, Melissa, Akhavein, Hassan, Holmes, Melissa F., Ozzoude, Miracle, Scott, Christopher JM, Gao, Fuqiang, Haddad, Seyyed MH, McLaughlin, Paula, Levine, Brian, Kwan, Donna, Montero-Odasso, Manuel, Finger, Elizabeth, McIlroy, William E, Lang, Anthony E., Tartaglia, Maria C., Mandzia, Jennifer, MacIntosh, Bradley J, Freedman, Morris, Rabin, Jennifer, Strother, Stephen C., Masellis, Mario, Symons, Sean, Bartha, Robert, Lim, Andrew, Swartz, Richard H, Black, Sandra E, and Goubran, Maged

Published
2024
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16. Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

Author

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, and Kumar, Sanjeev

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. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses

Author

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.

Published
2021
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18. Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Author

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.

Published
2023

19. Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales

Author

Fumagalli, Giorgio G., Basilico, Paola, Arighi, Andrea, Bocchetta, Martina, Dick, Katrina M., Cash, David M., Harding, Sophie, Mercurio, Matteo, Fenoglio, Chiara, Pietroboni, Anna M., Ghezzi, Laura, van Swieten, John, Borroni, Barbara, de Mendonça, Alexandre, Masellis, Mario, Tartaglia, Maria C., Rowe, James B., Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni B., Laforce, Jr, Robert, Finger, Elizabeth, Sorbi, Sandro, Scarpini, Elio, Rohrer, Jonathan D., Galimberti, Daniela, and on behalf of the Genetic FTD Initiative (GENFI)

Published
2018
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20. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH:A Longitudinal Multicentre Study

Author

Wilke, Carlo, Reich, Selina, van Swieten, John C., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Rohrer, Jonathan D., Synofzik, Matthis, Wilke, Carlo, Reich, Selina, van Swieten, John C., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Rohrer, Jonathan D., and Synofzik, Matthis

Abstract

Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD. ANN NEUROL 2022;91:33–47.

Published
2022

22. Geriatric dementia care at Ontario Shores: A new model of care

Author

Viau, Katelynn, Yaddaden, Amel, Lussier, Maxime, Bier, Nathalie, Earle, Julie, Duff-Woskosky, Andra, Bartfay, Wally, Desai, Chaitali, Zavitz, Karen, Horsburgh, Sheri, Gamble, Brenda, Lee, Linda, Hillier, Loretta M., Patel, Tejal, Molnar, Frank, Clarke, Jo-Anne, Borrie, Michael, Cammer, Allison, Morgan, Debra, Whiting, Susan, de Vos, Maya, Henri-Bhargava, Alexandre, Votova, Kristine, Delmar, Paul, Kerchner, Geoffrey A, Wang, Guoqiao, Bateman, Randall, Klein, Gregory, Andjelkovic, Mirjana, Abi-Saab, Danielle, Bullain, Szofia, Montoya, Alonso, Fontoura, Paulo, Doody, Rachelle, Tai, Elaine, Harvey, David, Hofmann, Carsten, Ristic, Smiljana, Rehal, Sunita, Voyle, Nicola, Baudler, Monika, Verreault, Phylicia, Rousseau, François, Keller, Evelyn, Simard, Alexandra, Azouaou, Nassima, Jarboui, Manel, Talleria, Lorraine, Duguay, Johanne, Mérette, Chantale, Labbé, Annie, de Arco, Rossana Peredo Nunez, Yous, Marie-Lee, Ploeg, Jenny, Kaasalainen, Sharon, Martin, Lori Schindel, Palumbo, Mary Val, Rambur, Betty, McKenna, Lori, Voyer, Philippe, Allaire, Émilie, Li, Bing, Thaut, Michael, Yogaparan, Thirumagal, Shanmuganathan, Thirunathan, Vickneswaran, Anicha, Sriharan, Sruthy, DeMarco, Mari L., Hsiung, Ging-Yuek Robin, Best, John R., Chertkow, Howard, Gauthier, Serge, Karlawish, Jason, Feldman, Howard, Spaner, Caroline, Christie, Brian, Musteata, Stela, Gawryluk, Jodie, Hofer, Scott, Henri-Bhargava, Alex, Kenny, Rebecca, Elliot, Valerie, Kosteniuk, Julie, Chow, Amanda Froehlich, Bayly, Melanie, O’Connell, Megan E., Kortzman, August, O’Connell, Megan, Kirk, Andrew, Conn, David, Sokoloff, Lisa, Feldman, Sid, Chau, James, Moser, Andrea, Lingum, Navena, Gingrich, Shaen, Shaikh, Salma, Rabheru, Kiran, Cassidy, Keri-Leigh, Checkland, Claire, Parsons, Daria, Massie, Ariane S., Mitchell, Julie Spence, Aksenchuk, Sophia, Lindsay, Barbara, Howard, Maria, Shaw, Courtney, Armitage, Gerrard, Capstick, Andrea, McNeil, Heather, Holyoke, Paul, Vines, Chanile, Giosa, Justine, Khan, Bilal, Shultz, Mary, BEAUCHET, Olivier, Sekhon, Harmehr, Allali, Gilles, Montembeault, Maxime, Brodeur, Catherine, Macoir, Joël, Maxwell, Colleen, Maclagan, Laura, Campitelli, Michael, Yao, Shenzhen, Dharma, Christoffer, Sherin, Tracey, Hogan, David, Bronskill, Susan, Ivo, Jessica, Faisal, Sadaf, McDougall, Aidan, Bauer, Jillian, Pritchard, Sarah, Chang, Feng, Mehta, Deval, Syed, Ali, Carter, Caitlin, Sharma, Shaambhavi, Nagge, Jeff, Naglie, Gary, Stasiulis, Elaine, Yamin, Stephanie, Vrkljan, Brenda, Tuokko, Holly, Sanford, Sarah, Porter, Michelle, Polgar, Jan, Myers, Anita, Moorhouse, Paige, Mazer, Barbara, Marshall, Shawn, Gélinas, Isabelle, Crizzle, Alexander, Byszewski, Anna, Belchior, Patricia, Bédard, Michel, Rapoport, Mark, Minish, Duane, Yetman, Linda, Stephenson, Margaret, McCloskey, Rose, Agbaku, Mansa, Jarrett, Pamela, Cavanagh, Jennifer, Loncar, Adele, Demers, Vickie, Gobessi, Linda, Lodha, Vinay, Scerbe, Andrea, Astell, Arlene, DesRoches, Andrea, Panyavin, Ivan, Feltz, Nick, Wittich, Walter, Aubin, Gabrielle, Hogan, Mariah, Swaminathan, Swathi, Altschuler, Aviva, Murphy, Kelly, Guthrie, Dawn, Williams, Nicole, Campos, Jennifer, Mick, Paul, Orange, Joseph B., Pichora-Fuller, M. Kathleen, Savundranayagam, Marie Y., Phillips, Natalie A., Giroud, Nathalie, Pichora-Fuller, Kathy, Al-Yawer, Faisal, Rehan, Sana, Phillips, Natalie, Beauchet, Olivier, Niculescu, Iulia, Iaboni, Andrea, Quirt, Hannah, Penko, Marion, Tsokas, Mario, Marshall, Cecelia, Flint, Alastair, McGilton, Katherine, O’Connell, Megan E, Stewart, Norma J, Seitz, Dallas, Daku, Jean, Hack, Tracy, Hoium, Faye, Kennett-Russill, Deb, Sauter, Kristen, Holley, Joanna, Wimhurst, Christine, Katchaluba, Janet, Mitchell, Debbie, Severina, Elmira, Dallaire-Théroux, Caroline, Saikali, Stéphan, Duchesne, Simon, Sivananthan, Saskia, Mirza, Saira, Saeed, Usman, Knight, Jo, Ramirez, Joel, Stuss, Donald, Yu, Di, Swardfager, Walter, Keith, Julia, Nestor, Sean, Black, Sandra, Masellis, Mario, Joyal, Marilyne, Kotz, Sonja A., Lenglos, Christophe, Renauld, Emmanuelle, Wilson, Maximiliano A., Fecteau, Shirley, Appel, Lora, Kisonas, Erika, Appel, Eva, Bartlett, Deanna, Klein, Jennifer, Rosenberg, Jarred, Smith, Christopher, Ali, Suad, Narang, Tanya, Wiseman, Micaela, Ein, Natalie, Orchanian-Cheff, Ani, Rylett, Jane, Hogan, David B., Rockwood, Kenneth, Dixon, Roger, Sun, Winnie, Hawkins, Stacey A., Awde, Carolee, Kay, Kelly, Huntsbarger, Deana, Ferrier, Erin, Sourial, Nadia, Arsenault-Lapierre, Genevieve, McAiney, Carrie, Vedel, Isabelle, Ingram, K. Jennifer, Frank, Andrew, Sabra, Iman, Wallace, Bruce, Breau, Michael, Sweet, Lisa, Goubran, Rafiq, Knoefel, Frank, Goubran, Rafik, Stroulia, Eleni, Ault, Laura, Kecskemet, Judith, Guseva, Elena, Lungu, Ovidiu, Goldman, Sondra, Wilchesky, Machelle, Johri, Fozia, Turner, Angelese, Lavoie, Monica, Tang-Wai, David, Leonard, Carol, Graham, Naida L., Rochon, Elizabeth, Middleton, Laura, Herrmann, Nathan, Oh, Paul, Regan, Kayla, Bechard, Lauren, Lanctôt, Krista, Freeman, Shannon, Pettersen, Jacqueline, Tomasone, Jennifer, Dupuis, Sherry, Giangregorio, Lora, Ferris, Rebecca, Stultz, Tim, Mallard, Kirsten, Campbell, Elaine, Chatterjee, Atri, Mackenzie, Ian, Reinshagen, Veronica Hirsh, Ducharme, Blake, Mousavi, Ali, Gill, Sascha, Mouches, Pauline, Wang, Meng, Rajasheskar, Deepthi, MacMaster, Frank, Forkert, Nils, Smith, Eric, Ismail, Zahinoor, Varatharajah, Breni, Camicioli, Richard, Gee, Myrlene, Zwiers, Angela, Sekhon, Ramnik, Charlton, Anna, Arsenault-Lapierre, Geneviève, Ingram, Jennifer, Hawkins, Stacey, Mousavi, SeyedAli, Mackenzie, Ian R. A., Hirsh-Reinshagen, Veronica, Hsiung, Ging-Yuek. R., Gillingham, Susan M.E., Anderson, Nicole D., Alain, Claude, Georgievski, Georgi, Alfaro, Leonardo, McClenaghan, Meridith, Soares, Daniela, Matheson, Maureen, Stanoulis, Krisanne, Boyle, Daniel, Chau, Linh, Pelc, Jordan, Snash, Nadia, Byrne, Joanne, Elalouf, Karine, Alfaro, Andrea Urqueta, Johnson, Aaron, Marinier, Julie-Andrée, Kehayia, Eva, Gagné, Jean-Pierre, Murphy, Caitlin, Ellen, Ruth, Flowers, Brandi, Boulton, Karen Lee, Subotic, Arsenije, McCreary, Cheryl R., Nguyen, Amanda, Saad, Feryal, Alvarez, Ana, Beaudin, Andrew E, Pike, Bruce, Smith, Eric E, Hu, Sophie, Patten, Scott, Fick, Gordon, Sapkota, Shraddha, Mirza, Saira Saeed, Scott, Christopher J., Stuss, Donald T., Black, Sandra E., Le Blanc, Gabriella, Ducharme, Simon, Meilleur-Durand, Synthia, Lévesque, Marianne, St-Onge, Frédéric, Cunnane, Stephen, Villeneuve, Sylvia, Callahan, Brandy, Laforce, Robert, Cetin-Sahin, Deniz, Cummings, Greta G., Schuster, Tibor, Karanofsky, Mark, De Jesus, Belmir J., Cassani, Raymundo, Cecchi, Marco, Fadem, K. C., McGeown, William J., Falk, Tiago H., Chu, Charlene, Zdaniuk, Natalia, Wang, Rosalie, Ouellet, Marie-Christine, Cassivi-Joncas, Alison, Godard-Sebillotte, Claire, Rochette, Louis, Pelletier, Eric, Strumpf, Erin, Margo-Dermer, Eva, Silver, Hilah, Vafaei, Rod, Fok, Alice C, Hsiung, Ging-Yuek R., Ursenbach, Jake, Bethell, Jennifer, Neuman, Mark D, Bateman, Brian T, Hill, Andrea, Wunsch, Hannah, Ritchie, Kim, Cramm, Heidi, Aiken, Alice, Donnelly, Catherine, Goldie, Katie, Delara, Mahin, Ozzoude, Miracle, Varriano, Brenda, McLaughlin, Paula, Troyer, Angela, Bartha, Robert, Symons, Sean, Kwan, Donna, Tan, Brian, Swartz, Richard H., Saposnik, Gustavo, Tartaglia, Maria C., Ahuja, Manan, Siddhpuria, Shailee, Gormley, Jessica, Reppas, Christina, Wong, Eric, Lee, Justin, Patterson, Christopher, Walker, Jennifer, Warry, Wayne, Blind, Melissa, Allaby, Cheryl, Pitawanakwat, Karen, Zhao, Yantao, Lemieux, Andrine, Jacklin, Kristen, Crowshoe, Lindsay, Boehme, Gail, McKenna, Betty, Boyling, Elaine, Webkamigad, Sharlene, Bigeagle, Louise, Akan, Nicole, Wallace, Lindsay, Theou, Olga, Bennett, David, Darvesh, Sultan, Kirkland, Susan, Fisk, John, Andrew, Melissa, Cullen, Stephanie, Carroll, Susan, Mahon, Joel, Sarquis-Adamson, Yanina, Montero-Odasso, Manuel, Sharma, Nabina, Beaton, Derek, Roberts, Angela, Munoz, Doug, Swartz, Richard, Breen, David, Lang, Anthony, Fischer, COrrine, Fischer, Corrine, Kumar, Sanjeeve, Freedman, Morris, Finger, Elizabeth, Zinman, Lorne, Grimes, David A., Sunderland, Kelly M., Binns, Malcolm A., Strother, Stephen C., Mandzia, Jennifer, Orange, JB, Tartaglia, Carmela, El Shatshat, Amna, Rao, Praveen P.N., Teves, Julia, Bodkin, R Jack, Ho, Joanne M-W, Mehdizadeh, Sina, Dolatabadi, Elham, Ng, Kimberley-Dale, Arora, Twinkle, Jizmejian, Melody, Mansfield, Avril, Taati, Babak, Levy, Jake, Savard, Melissa, Pascoal, Tharick, Soucy, Jean-Paul, Rosa-Neto, Pedro, Martins, Felicia, Waller, Shannon, Flora, Parminder, Morland, Chris, Donovan, Steve, Fels, Deborah, Desai, Shital, Boger, Jennifer, Shashtri, Karan, Persaud, Deanna, Marashi, Sheida, Nedlund, Ann-Charlotte, Mäki-Petäjä-Leinonen, Anna, Nygård, Louise, Issakainen, Mervi, ryd, Charlotta, Pan, Yuhan, Joddrell, Phil, Dove, Erica, Owens, Hollis, Park, Elly, Liu, Lili, Kaufman, David, Simonian, Natalie, Chen, Ying, Sunderland, Kelly, Fraser, Julia, Swartz, Rick, Strother, Stephen, Legrand, Diego, Roberge, Pasquale, Vanasse, Alain, Bocti, Christian, Pirrie, Lorraine, Gray, Carolyn Steele, Nippak, Pria, Coughlan, Dave, Teselink, Johannes, Hermann, Nathan, Rasquinha, Fawn, Lanctot, Krista, Webber, Jodi, Woo, Kevin, Chamoun, Elicia, Coulombe, Valérie, Sellami, Leila, Paquette-Raynard, Emmanuelle, Gardner, Sandra, van Zon, Lorraine, Moy, Sally, Sidrak, Mariam, Sternhill, Janis, Feldman, Sidney, Karuza, Jurgis, Berall, Anna, Thomas, Neil, Mattek, Nora, Riley, Thomas, Reynolds, Christina, Marcoe, Jennifer, Sharma, Nicole, Kaye, Jeffrey, Jagtap, Shreya, Rotenberg, Shlomit, Vandermorris, Susan, Anderson, ND, Dawson, DR, Chater, Catherine, Soor, Jaspreet, Ji, Xiang, Koo, Morgan, Compagnone, Jordana, Kertes, Peter, Juby, Angela, Mager, Diana, Davis, Christopher, Jay, David, Blackburn, Toni, Brocks, Dion, Lee, Hyunwoo, Wiggermann, Vanessa, Rauscher, Alexander, Lam, Kevin, Tam, Roger, Popuri, Karteek, Beg, Mirza Faisal, Jacova, Claudia, Sossi, Vesna, Bindra, Jessica, Bouvier, Liziane, Monetta, Laura, Vitali, Paolo, Martel-Sauvageau, Vincent, Godin, Judith, McNeil, Shelly, McElhaney, Janet, Laughton, Thomas, Ho, Joanne, Tung, Jennifer, Dubé, Joseph B., Lin, Tianzhen, Best, Sarah, Truemner, Julia, Sargeant, Patricia L., Borrie, Michael J., Fogarty, Jennifer, Bassi, Nimi, Di Prospero, Cynthia, Whitehead, Victor, Pilon, Randi, Wong, Timothy, Elhayek, Nada, Dasgupta, Monidipa, Davis, Daniel, ORegan, Niamh, Kröger, Edeltraut, Furrer, Daniela, Wilcheski, Machelle, Morin, Michèle, Carmichael, Pierre-Hugues, Champoux, Nathalie, Monette, Johanne, Giguère, Anik, Aubin, Michèle, Durand, Pierre, Whiteside, Jena, Mele, Bria, Merrikh, Daria, Goodarzi, Zahra, Seary, Judith Anne, Bulley, Heather, Diciacca, Allison, Esseltine, Julia, Gaiger, Erin, Jankovic, Ivana, Mackenzie, Stephanie, McBride, Meghan, Knopp-Sihota, Jennifer A., Hoben, Mathias, Poss, Jeffrey W., Rachor, Geoffrey S., Estabrooks, Carole A., and Iroanyah, Ngozi

Subjects
Abstracts: Posters
Published
2020

23. Faster Cortical Thinning and Surface Area Loss in Presymptomatic and Symptomatic C9orf72 Repeat Expansion Adult Carriers

Author

Le Blanc, Gabriella, Jetté Pomerleau, Vincent, Graff, Caroline, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Masellis, Mario, Tábuas‐Pereira, Miguel, Tainta, Mikel, Tang‐Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Tartaglia, Maria C., Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Mendonça, Alexandre, Santana, Isabel, Butler, Chris, McCarthy, Jillian, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Sorbi, Sandro, Rohrer, Jonathan D., Ducharme, Simon, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Borroni, Barbara, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Swieten, John, Black, Sandra, Bocchetta, Martina, Borrego, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Galimberti, Daniela, Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B., Flanagan, Toby, Fox, Nick, Sanchez‐Valle, Raquel, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, LaForce, Robert, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Moreno, Fermin, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Synofzik, Matthis, Olives, Jaume, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Pijnenburg, Yolande, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Neurology, Ducharme, Simon [0000-0002-7309-1113], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, diagnostic imaging [Frontotemporal Dementia], 03 medical and health sciences, Young Adult, 0302 clinical medicine, Atrophy, C9orf72, Internal medicine, diagnostic imaging [Cerebral Cortex], medicine, Humans, ddc:610, Young adult, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Aged, Aged, 80 and over, Cerebral Cortex, DNA Repeat Expansion, medicine.diagnostic_test, C9orf72 Protein, business.industry, Magnetic resonance imaging, diagnostic imaging [Atrophy], Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Neurology, Cerebral cortex, Frontotemporal Dementia, Cardiology, Female, Neurology (clinical), Trinucleotide repeat expansion, business, Asymptomatic carrier, 030217 neurology & neurosurgery, Frontotemporal dementia, genetics [Atrophy]
Abstract

Objective C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. Methods Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1-weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex-wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age-matched controls using mixed-effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the "age by genetic status" interaction. False discovery rate corrections were applied to all vertex-wide analyses. Results The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18-86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. Interpretation C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113-122.

Published
2020

24. Longitudinal relationships between cognitive domains and depression and anxiety symptoms in systemic lupus erythematosus

Author

Bingham, Kathleen S., primary, DiazMartinez, JuanPablo, additional, Green, Robin, additional, Tartaglia, Maria C., additional, Ruttan, Lesley, additional, Su, Jiandong, additional, Wither, Joan E., additional, Kakvan, Mahta, additional, Anderson, Nicole, additional, Bonilla, Dennisse, additional, Choi, May Y., additional, Fritzler, Marvin J., additional, Beaton, Dorcas E., additional, Katz, Patti, additional, and Touma, Zahi, additional

Published
2021
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25. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study

Author

Wilke, Carlo, Reich, Selina, Swieten, John C., Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego‐Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Peakman, Georgia, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas‐Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang‐Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rohrer, Jonathan D., Synofzik, Matthis, Repositório da Universidade de Lisboa, Neurology, and Clinical Genetics

Subjects
blood [Frontotemporal Dementia], Male, Oncology, Medizin, blood [Neurofilament Proteins], Disease, Cohort Studies, 0302 clinical medicine, Settore BIO/13 - Biologia Applicata, Neurofilament Proteins, C9orf72, CRITERIA, Longitudinal Studies, Stage (cooking), 0303 health sciences, blood [Biomarkers], FTD, Middle Aged, 3. Good health, Neurology, Frontotemporal Dementia, Cohort, Biomarker (medicine), Female, Life Sciences & Biomedicine, Frontotemporal dementia, Treatment response, medicine.medical_specialty, Clinical Neurology, C9ORF72, IMMUNOASSAY, 03 medical and health sciences, Atrophy, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, medicine, Humans, ddc:610, Aged, 030304 developmental biology, Science & Technology, HEXANUCLEOTIDE REPEAT, MUTATIONS, business.industry, DISEASE PROGRESSION, Neurosciences, medicine.disease, Biomarkers, Neurosciences & Neurology, Neurology (clinical), TAU, business, 030217 neurology & neurosurgery
Abstract

© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD., W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID No. 739510. This work was supported by the Horizon 2020 research and innovation program (grant 779257 Solve-RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), the EU Joint Programme – Neurodegenerative Disease Research (JPND) “GENFI-prox” through participating national funding agencies (by DLR/BMBF to M.S., J.D.R., B.B., C.G., and M.O.), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 643417. J.C.S. and H.S. received funding by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813 and 733050103) in the Netherlands and the Bluefield Project to Cure Frontotemporal Dementia. J.B.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (SUAG/051 G101400). C.B. is supported by a postdoctoral fellowship from the Swiss National Science Foundation (P400PM_191077). J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248).

Published
2021

26. Functional Brain Signals Constrained by Structural Brain Connectivity Reveal Cohort Specific Features for Serum Neurofilament Light Chain

Author

Sihag, Saurabh, Naze, S��bastien, Taghdiri, Foad, Gumus, Melisa, Tator, Charles, Green, Robin, Colella, Brenda, Blennow, Kaj, Zetterberg, Henrik, Dominguez, Luis Garcia, Wennberg, Richard, Mikulis, David J., Tartaglia, Maria C., and Kozloski, James R.

Abstract

Supporting data and code for results in 'Functional Brain Signals Constrained by Structural Brain Connectivity Reveal Cohort Specific Features for Serum Neurofilament Light Chain'.&nbsp

Published
2021
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28. Small and Large Magnetic Resonance Imaging–Visible Perivascular Spaces in the Basal Ganglia of Parkinson's Disease Patients.

Author

Ramirez, Joel, Berberian, Stephanie A., Breen, David P., Gao, Fuqiang, Ozzoude, Miracle, Adamo, Sabrina, Scott, Christopher J.M., Berezuk, Courtney, Yhap, Vanessa, Mestre, Tiago A., Marras, Connie, Tartaglia, Maria C., Grimes, David, Jog, Mandar, Kwan, Donna, Tan, Brian, Binns, Malcolm A., Arnott, Stephen R., Bartha, Robert, and Symons, Sean

Abstract

Background: Although previously thought to be asymptomatic, recent studies have suggested that magnetic resonance imaging–visible perivascular spaces (PVS) in the basal ganglia (BG‐PVS) of patients with Parkinson's disease (PD) may be markers of motor disability and cognitive decline. In addition, a pathogenic and risk profile difference between small (≤3‐mm diameter) and large (>3‐mm diameter) PVS has been suggested. Objective: The aim of this study was to examine associations between quantitative measures of large and small BG‐PVS, global cognition, and motor/nonmotor features in a multicenter cohort of patients with PD. Methods: We performed a cross‐sectional study examining the association between large and small BG‐PVS with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Parts I–IV and cognition (Montreal Cognitive Assessment) in 133 patients with PD enrolled in the Ontario Neurodegenerative Disease Research Initiative study. Results: Patients with PD with small BG‐PVS demonstrated an association with MDS‐UPDRS Parts I (P = 0.008) and II (both P = 0.02), whereas patients with large BG‐PVS demonstrated an association with MDS‐UPDRS Parts III (P < 0.0001) and IV (P < 0.001). BG‐PVS were not correlated with cognition. Conclusions: Small BG‐PVS are associated with motor and nonmotor aspects of experiences in daily living, while large BG‐PVS are associated with the motor symptoms and motor complications. © 2022 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2022
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29. Cortical Thickness Estimation in Individuals With Cerebral Small Vessel Disease, Focal Atrophy, and Chronic Stroke Lesions

Author

Ozzoude, Miracle, primary, Ramirez, Joel, additional, Raamana, Pradeep Reddy, additional, Holmes, Melissa F., additional, Walker, Kirstin, additional, Scott, Christopher J. M., additional, Gao, Fuqiang, additional, Goubran, Maged, additional, Kwan, Donna, additional, Tartaglia, Maria C., additional, Beaton, Derek, additional, Saposnik, Gustavo, additional, Hassan, Ayman, additional, Lawrence-Dewar, Jane, additional, Dowlatshahi, Dariush, additional, Strother, Stephen C., additional, Symons, Sean, additional, Bartha, Robert, additional, Swartz, Richard H., additional, and Black, Sandra E., additional

Published
2020
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30. PET Tau Imaging and Motor Impairments Differ Between Corticobasal Syndrome and Progressive Supranuclear Palsy With and Without Alzheimer's Disease Biomarkers

Author

Vasilevskaya, Anna, primary, Taghdiri, Foad, additional, Multani, Namita, additional, Anor, Cassandra, additional, Misquitta, Karen, additional, Houle, Sylvain, additional, Burke, Charles, additional, Tang-Wai, David, additional, Lang, Anthony E., additional, Fox, Susan, additional, Slow, Elizabeth, additional, Rusjan, Pablo, additional, and Tartaglia, Maria C., additional

Published
2020
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31. Interaction of APOE4 alleles and PET tau imaging in former contact sport athletes

Author

Vasilevskaya, Anna, primary, Taghdiri, Foad, additional, Burke, Charles, additional, Tarazi, Apameh, additional, Naeimi, Seyed Ali, additional, Khodadadi, Mozghan, additional, Goswami, Ruma, additional, Sato, Christine, additional, Grinberg, Mark, additional, Moreno, Danielle, additional, Wennberg, Richard, additional, Mikulis, David, additional, Green, Robin, additional, Colella, Brenda, additional, Davis, Karen D., additional, Rusjan, Pablo, additional, Houle, Sylvain, additional, Tator, Charles, additional, Rogaeva, Ekaterina, additional, and Tartaglia, Maria C., additional

Published
2020
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32. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study.

Author

Wilke, Carlo, Reich, Selina, van Swieten, John C., Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., and Gerhard, Alexander

Subjects
FRONTOTEMPORAL dementia, CEREBRAL atrophy, LONGITUDINAL method, GENETIC mutation, INDIVIDUALIZED medicine
Abstract

Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker‐based stratification and biomarker cascade of the likely most treatment‐relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single‐molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation‐negative within‐family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra‐individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage‐dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity‐to‐onset. We estimate stage‐dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage‐dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker‐based precision medicine approach to genetic FTD. ANN NEUROL 2022;91:33–47 [ABSTRACT FROM AUTHOR]

Published
2022
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34. Severity dependent distribution of impairments in PSP and CBS: Interactive Visualizations

Author

Brittain, Claire, McCarthy, Andrew, investigators, PROPSPERA, Tolosa, E., Buongiorno, M. T., Bargalló, N., Burguera, J. A., Martinez, I., Ruiz-Mart'ınez, J., Narrativel, I., Vivancos, F., Ybot, I., Aguilar, M., 4RNTI-1authors, Quilez, P., Boada, M., Lafuente, A., Hernandez, I., López-Lozano, J. J., Mata, M., Kupsch, A., Lipp, A., Ebersbach, G., Schmidt, T., PSP, Tau Restoration on, Hahn, K., Höllerhage, M., Oertel, W. H., Respondek, G., Stamelou, M., Reichmann, H., Wolz, M., Schneider, C., Klingelhöfer, L., Berg, D., Williams, David, Maetzler, W., Srulijes, K. K., Ludolph, A., Kassubek, J., Steiger, M., Tyler, K., Burn, D. J., Morris, L., Lees, A., Ling, H., Lafontaine, Anne Louise, Hauser, R., McClain, T., Truong, D., Jenkins, S., Litvan, I., Houghton, D., Ferrara, J., Bordelon, Y., Gratiano, A., Golbe, L., Marras, Connie, Mark, M., Uitti, R., Ven Gerpen, J., Jog, Mandar, Panisset, Michael, Lang, Anthony, Parker, Lesley, Irizarry, Michael C, Stewart, Alistair J, Corvol, Jean-Christophe, Azulay, Jean-Philippe, Couratier, Philippe, Mollenhauer, Brit, Lorenzl, Stefan, Ludolph, Albert, Benecke, Reiner, Lipp, Axel, Reichmann, Heinz, McDermott, Dana, Woitalla, Dirk, Chan, Dennis, Zermansky, Adam, Burn, David, Lees, Andrew, Gozes, Illana, Boxer, Adam, Miller, Bruce L, Lobach, Iryna V, Roberson, Erik, Biglan, Kevin, Honig, Lawrence, Zamrini, Edward, Pahwa, Rajesh, Bordelon, Yvette, Driver-Dunkley, Erika, Lessig, Stephanie, Lew, Mark, Womack, Kyle, Boeve, Brad, Ferrara, Joseph, Höglinger, Günter U, Hillis, Argyle, Kaufer, Daniel, Kumar, Rajeev, Xie, Tao, Gunzler, Steven, Zesiewicz, Theresa, Dayalu, Praveen, Golbe, Lawrence, Grossman, Murray, Jankovic, Joseph, McGinnis, Scott, Santiago, Anthony, Tuite, Paul, Isaacson, Stuart, Leegwater-Kim, Julie, Litvan, Irene, Knopman, David S, Schneider, Lon S, Doody, Rachelle S, Del Ser, Teodoro, Golbe, Lawrence I, Roberson, Erik D, Koestler, Mary, Jack, Clifford R, Van Deerlin, Viviana, Randolph, Christopher, Whitaker, Steve, Hirman, Joe, Gold, Michael, Morimoto, Bruce H, Boxer, Adam L, Nuebling G, Georg, Hensler, Mira, Paul, Sabine, Zwergal, Andreas, Heuer, Hilary W, Tartaglia, Maria C, McGinnis, Scott M, Dickerson, Bradford C, Kornak, John, Group, AL-108-231 Study, Schuff, Norbert, Rabinovici, Gil D, Rosen, Howard J, Gómez, J. C., Tijero, B., Berganzo, K., Garc'ıa de Yebenes, J., Lopez Sendón, J. L., and Garcia, G.

Subjects
0301 basic medicine, Male, Activities of daily living, physiopathology [Supranuclear Palsy, Progressive], Disease, Severity of Illness Index, diagnosis [Supranuclear Palsy, Progressive], Predictive models, 0302 clinical medicine, diagnosis [Basal Ganglia Diseases], Aged, 80 and over, Neurodegenerative Diseases, Syndrome, Middle Aged, Corticobasal syndrome, Prognosis, Neurology, Disease Progression, Female, Tauopathy, Supranuclear Palsy, Progressive, Natural history study, PSP rating scale, medicine.medical_specialty, physiopathology [Basal Ganglia Diseases], diagnosis [Neurodegenerative Diseases], Models, Neurological, Article, Progressive supranuclear palsy, 03 medical and health sciences, Physical medicine and rehabilitation, Basal Ganglia Diseases, Rating scale, medicine, Humans, ddc:610, Aged, Interactive visualizations, business.industry, physiopathology [Neurodegenerative Diseases], Data Visualization, medicine.disease, Gait, eye diseases, Clinical trial, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

Background: Progressive supranuclear palsy (PSP)-Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. Objectives: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. Methods: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. Results: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. Conclusion: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

Published
2018

35. Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

Author

Brittain, Claire, primary, McCarthy, Andrew, additional, Irizarry, Michael C., additional, McDermott, Dana, additional, Biglan, Kevin, additional, Höglinger, Günter U., additional, Lorenzl, Stefan, additional, del Ser, Teodoro, additional, Boxer, Adam L., additional, Williams, David, additional, Lafontaine, Anne Louise, additional, Marras, Connie, additional, Jog, Mandar, additional, Panisset, Michael, additional, Lang, Anthony, additional, Parker, Lesley, additional, Stewart, Alistair J., additional, Corvol, Jean-Christophe, additional, Azulay, Jean-Philippe, additional, Couratier, Philippe, additional, Mollenhauer, Brit, additional, Ludolph, Albert, additional, Benecke, Reiner, additional, Hoglinger, Gunter, additional, Lipp, Axel, additional, Reichmann, Heinz, additional, Woitalla, Dirk, additional, Chan, Dennis, additional, Zermansky, Adam, additional, Burn, David, additional, Lees, Andrew, additional, Gozes, Illana, additional, Boxer, Adam, additional, Miller, Bruce L., additional, Lobach, Iryna V., additional, Roberson, Erik, additional, Honig, Lawrence, additional, Zamrini, Edward, additional, Pahwa, Rajesh, additional, Bordelon, Yvette, additional, Driver-Dunkley, Erika, additional, Lessig, Stephanie, additional, Lew, Mark, additional, Womack, Kyle, additional, Boeve, Brad, additional, Ferrara, Joseph, additional, Hillis, Argyle, additional, Kaufer, Daniel, additional, Kumar, Rajeev, additional, Xie, Tao, additional, Gunzler, Steven, additional, Zesiewicz, Theresa, additional, Dayalu, Praveen, additional, Golbe, Lawrence, additional, Grossman, Murray, additional, Jankovic, Joseph, additional, McGinnis, Scott, additional, Santiago, Anthony, additional, Tuite, Paul, additional, Isaacson, Stuart, additional, Leegwater-Kim, Julie, additional, Litvan, Irene, additional, Knopman, David S., additional, Schneider, Lon S., additional, Doody, Rachelle S., additional, Golbe, Lawrence I., additional, Roberson, Erik D., additional, Koestler, Mary, additional, Jack, Clifford R., additional, Van Deerlin, Viviana, additional, Randolph, Christopher, additional, Whitaker, Steve, additional, Hirman, Joe, additional, Gold, Michael, additional, Morimoto, Bruce H., additional, Nuebling G, Georg, additional, Hensler, Mira, additional, Paul, Sabine, additional, Zwergal, Andreas, additional, Heuer, Hilary W., additional, Tartaglia, Maria C., additional, McGinnis, Scott M., additional, Dickerson, Bradford C., additional, Kornak, John, additional, Schuff, Norbert, additional, Rabinovici, Gil D., additional, Rosen, Howard J., additional, Gómez, J.C., additional, Tijero, B., additional, Berganzo, K., additional, Garc'ıa de Yebenes, J., additional, Lopez Sendón, J.L., additional, Garcia, G., additional, Tolosa, E., additional, Buongiorno, M.T., additional, Bargalló, N., additional, Burguera, J.A., additional, Martinez, I., additional, Ruiz-Mart'ınez, J., additional, Narrativel, I., additional, Vivancos, F., additional, Ybot, I., additional, Aguilar, M., additional, Quilez, P., additional, Boada, M., additional, Lafuente, A., additional, Hernandez, I., additional, López-Lozano, J.J., additional, Mata, M., additional, Kupsch, A., additional, Lipp, A., additional, Ebersbach, G., additional, Schmidt, T., additional, Hahn, K., additional, Höglinger, G., additional, Höllerhage, M., additional, Oertel, W.H., additional, Respondek, G., additional, Stamelou, M., additional, Reichmann, H., additional, Wolz, M., additional, Schneider, C., additional, Klingelhöfer, L., additional, Berg, D., additional, Maetzler, W., additional, Srulijes, K.K., additional, Ludolph, A., additional, Kassubek, J., additional, Steiger, M., additional, Tyler, K., additional, Burn, D.J., additional, Morris, L., additional, Lees, A., additional, Ling, H., additional, Hauser, R., additional, McClain, T., additional, Truong, D., additional, Jenkins, S., additional, Litvan, I., additional, Houghton, D., additional, Ferrara, J., additional, Bordelon, Y., additional, Gratiano, A., additional, Golbe, L., additional, Mark, M., additional, Uitti, R., additional, and Ven Gerpen, J., additional

Published
2019
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37. Examining perivascular spaces (PVS) in cerebral small vessel disease (CSVD) using a novel T1- based automated PVS segmentation tool

Author

Gibson, Erin, Ramirez, Joel, Woods, Lauren A., Sommers, Rosa, Ghahjaverestan, Nasim M., Scott, Christopher J.M., Gao, Fuqiang, Lang, Anthony E., Marras, Connie, Breen, David P., Tartaglia, Maria C., Binns, Malcolm A., Bartha, Robert, Symons, Sean, Swartz, Richard H., Masellis, Mario, Black, Sandra E., Moody, Alan, Lim, Andrew SP, and Goubran, Maged

Abstract

White matter hyperintensities (WMH) and MRI-visible perivascular spaces (PVS) are neuroimaging features of cerebral small vessel disease (CSVD). PVS are believed to play a role in cerebral metabolic waste clearance, particularly during sleep, and emerging evidence suggests that sleep disturbances are among the earliest symptoms of dementia. However, PVS quantification remains challenging and not accessible, particularly in complex patients with neurovascular and neurodegenerative disease. We developed and validated an automated deep learning-based PVS quantification method using multi-site patient MRI with varying degrees of CSVD burden. Additionally, we examined the correlation between PVS volumes and age in patients undergoing treatment for sleep apnea.

Published
2024
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38. Associations between MRI-visible perivascular spaces, brain atrophy, white matter hyperintensities, and speeded executive function, in neurodegenerative and cerebrovascular diseases.

Author

Andriuta, Daniela, Ramirez, Joel, Gao, Fuqiang, Rabin, Jennifer, Wood, Madeline E, McLaughlin, Paula M, Scott, Christopher JM, Ozzoude, Miracle, Dilliott, Allison A, Hegele, Robert A, Tartaglia, Maria C, Tang-Wai, David, Swartz, Richard H, Casaubon, Leanne, Kumar, Sanjeev, Dowlatshahi, Dar, Mandzia, Jennifer, Sahlas, Demetrios, Saposnik, Gustavo, Fischer, Corinne, Borrie, Michael, Hassan, Ayman, Binns, Malcolm A, Freedman, Morris, Finger, Elizabeth, Frank, Andrew, Bartha, Robert, Symons, Sean, Masellis, Mario, and Black, Sandra E

Abstract

MRI-visible perivascular spaces (PVS) are a neuroimaging feature of cerebral small vessel disease and are commonly observed in patients with cerebrovascular and neurodegenerative disease. However, it is unclear whether PVS burden is associated with cognition. The aim of this study was to investigate the potential associations between PVS volumes, brain atrophy, white matter hyperintensities (WMH), and speeded executive function, in patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).

Published
2024
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39. Neurofilament light chain: a biomarker for genetic frontotemporal dementia

Author

Meeter, Lieke H., primary, Dopper, Elise G., additional, Jiskoot, Lize C., additional, Sanchez-Valle, Raquel, additional, Graff, Caroline, additional, Benussi, Luisa, additional, Ghidoni, Roberta, additional, Pijnenburg, Yolande A., additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Laforce, Robert Jr, additional, Masellis, Mario, additional, Vandenberghe, Rik, additional, Ber, Isabelle Le, additional, Otto, Markus, additional, van Minkelen, Rick, additional, Papma, Janne M., additional, Rombouts, Serge A., additional, Balasa, Mircea, additional, Öijerstedt, Linn, additional, Jelic, Vesna, additional, Dick, Katrina M., additional, Cash, David M., additional, Harding, Sophie R., additional, Jorge Cardoso, M., additional, Ourselin, Sebastien, additional, Rossor, Martin N., additional, Padovani, Alessandro, additional, Scarpini, Elio, additional, Fenoglio, Chiara, additional, Tartaglia, Maria C., additional, Lamari, Foudil, additional, Barro, Christian, additional, Kuhle, Jens, additional, Rohrer, Jonathan D., additional, Teunissen, Charlotte E., additional, and van Swieten, John C., additional

Published
2016
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40. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability.

Author

Finger, Elizabeth C, Finger, Elizabeth C, MacKinley, Julia, Blair, Mervin, Oliver, Lindsay D, Jesso, Sarah, Tartaglia, Maria C, Borrie, Michael, Wells, Jennie, Dziobek, Isabel, Pasternak, Stephen, Mitchell, Derek GV, Rankin, Katherine, Kertesz, Andrew, Boxer, Adam, Finger, Elizabeth C, Finger, Elizabeth C, MacKinley, Julia, Blair, Mervin, Oliver, Lindsay D, Jesso, Sarah, Tartaglia, Maria C, Borrie, Michael, Wells, Jennie, Dziobek, Isabel, Pasternak, Stephen, Mitchell, Derek GV, Rankin, Katherine, Kertesz, Andrew, and Boxer, Adam

Abstract

ObjectiveTo determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD).MethodsWe conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects.ResultsAll 3 doses of intranasal oxytocin were safe and well tolerated.ConclusionsA multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD.Classification of evidenceThis study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.

Published
2015

41. Neurodegenerative Disease Phenotypes In Carriers Of Mapt P.A152T, A Risk Factor For Frontotemporal Dementia Spectrum Disorders And Alzheimer Disease

Author

Lee, Suzee E., Tartaglia, Maria C., Yener, Goersev, Genc, Sermin, Seeley, William W., Sanchez-Juan, Pascual, Moreno, Fermin, Mendez, Mario F., Klein, Eric, Rademakers, Rosa, Lopez de Munain, Adolfo, Combarros, Onofre, Kramer, Joel H., Kenet, Robert O., Boxer, Adam L., Geschwind, Michael D., Gorno-Tempini, Maria-Luisa, Karydas, Anna M., Rabinovici, Gil D., and Coppola, Giovanni

Subjects
mental disorders
Abstract

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

Published
2013

44. Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 Mutations

Author

Zhang, Zhijun, primary, Almeida, Sandra, additional, Lu, Yubing, additional, Nishimura, Agnes L., additional, Peng, Lingtao, additional, Sun, Danqiong, additional, Wu, Bei, additional, Karydas, Anna M., additional, Tartaglia, Maria C., additional, Fong, Jamie C., additional, Miller, Bruce L., additional, Farese, Robert V., additional, Moore, Melissa J., additional, Shaw, Christopher E., additional, and Gao, Fen-Biao, additional

Published
2013
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48. In search of evidence-based treatment for concussion: characteristics of current clinical trials.

Author

Burke, Matthew J., Fralick, Michael, Nejatbakhsh, Nasrin, Tartaglia, Maria C., and Tator, Charles H.

Subjects
ALTERNATIVE medicine, BRAIN concussion, CLINICAL trials, COGNITIVE therapy, COMBINED modality therapy, DIETARY supplements, HEALTH care teams, HYPERBARIC oxygenation, NEUROPSYCHOLOGICAL tests, RESEARCH methodology, EVALUATION of medical care, MEDICAL rehabilitation, HEALTH outcome assessment, PATIENTS, PHOTOTHERAPY, PHYSICAL therapy, QUESTIONNAIRES, SYSTEMATIC reviews, EVIDENCE-based medicine, PROFESSIONAL practice, SOCIOECONOMIC factors, CLINICAL trial registries, REHABILITATION for brain injury patients, DESCRIPTIVE statistics
Abstract

Objective: To assess the characteristics of current clinical trials investigating the treatment of concussion. Background: Recent systematic literature reviews have concluded that there is minimal evidence to support any specific treatment for concussion, including the principles of return-to-activity protocols such as type or duration of rest. Design/methods: Clinical trial data was extracted from Clinicaltrials.gov and seven additional World Health Organization primary registries. The trial databases were accessed up until 3 October 2013. This study used search terms of 'concussion' or 'mild traumatic brain injury' (mTBI) and filtered for interventional trials. Trials that were terminated, already published or not interventional trials of concussion/mTBI were excluded. Results: Of the 142 concussion/mTBI interventional clinical trials identified, 71 met inclusion criteria. Trials had a median estimated enrolment of 60 participants. There was a wide-range of treatments studied, including cognitive/behavioural therapies (28.2%), medications (28.2%), devices (11.3%), dietary supplements (8.5%), return-to-activity/rest (1.4%) and others (22.4%). Heterogeneity among trials for concussion identification/diagnosis and primary outcomes utilized was evident. Symptom-based questionnaires (39.4%) and neuropsychological tests (28.2%) were the most common outcome measures. Conclusions: Diverse, potentially promising therapeutics are currently being studied for the treatment of concussion. However, several deficiencies were identified including a paucity of trials addressing return-to-activity principles. Also, small sample size and trial heterogeneity may threaten scientific evaluation and subsequent clinical application. [ABSTRACT FROM AUTHOR]

Published
2015
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49. Fatigue in Multiple Sclerosis and Post-Poliomyelitis Syndrome.

Author

Trojan, Daria A., Arnold, Douglas L., Shapiro, Stan, Bernasconi, Andrea, Le Cruguel, Jean-Pierre, Narayanan, Sridar, Wong, Amy N., Tartaglia, Maria C., Lapierre, Yues, Costa, Deborah Da, Collet, Jean-Paul, Bar-Or, Amit, Robinson, Ann, Ducruet, Thierry, Arcelin, Katia, and Caramanos, Zografos

Published
2006

50. Fatigue in Multiple Sclerosis and PostPoliomyelitis Syndrome

Author

Trojan, Daria A., Arnold, Douglas L., Shapiro, Stan, Bernasconi, Andrea, Le Cruguel, Jean-Pierre, Narayanan, Sridar, Wong, Amy N., Tartaglia, Maria C., Lapierre, Yues, Costa, Deborah Da, Collet, Jean-Paul, Bar-Or, Amit, Robinson, Ann, Ducruet, Thierry, Arcelin, Katia, and Caramanos, Zografos

Published
2006

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