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JOURNAL ARTICLE
Laynie Dratch, Jill Owczarzak, Weiyi Mu, Katheryn A Q Cousins, Lauren Massimo, Murray Grossman, Lori Erby
With the increasing availability of predictive genetic testing for adult-onset neurodegenerative conditions, it is imperative that we better understand the impact of learning one's risk status. Frontotemporal degeneration (FTD) is the second most prevalent cause of early-onset dementia. About one-third of patients have an identifiable genetic etiology, and some genetic variants that cause FTD can also cause amyotrophic lateral sclerosis (ALS). To understand individuals' risk perception and broader experience of living at risk, we completed semi-structured telephone interviews with 14 asymptomatic adults who tested positive for a variant known to cause risk for FTD and/or ALS...
July 10, 2023: Journal of Genetic Counseling
#22
JOURNAL ARTICLE
Sharon Ash, Naomi Nevler, David J Irwin, Sanjana Shellikeri, Katya Rascovsky, Leslie Shaw, Edward B Lee, John Q Trojanowski, Murray Grossman
BACKGROUND: Apraxia of speech (AOS) is a core feature of nonfluent/agrammatic primary progressive aphasia (naPPA), but its precise characteristics and the prevalence of AOS features in spontaneous speech are debated. OBJECTIVE: To assess the frequency of features of AOS in the spontaneous, connected speech of individuals with naPPA and to evaluate whether these features are associated with an underlying motor disorder such as corticobasal syndrome or progressive supranuclear palsy...
2023: JAD Reports
#23
JOURNAL ARTICLE
Antemortem network analysis of spreading pathology in autopsy-confirmed frontotemporal degeneration.
Min Chen, Sarah Burke, Christopher A Olm, David J Irwin, Lauren Massimo, Edward B Lee, John Q Trojanowski, James C Gee, Murray Grossman
Despite well-articulated hypotheses of spreading pathology in animal models of neurodegenerative disease, the basis for spreading neurodegenerative pathology in humans has been difficult to ascertain. In this study, we used graph theoretic analyses of structural networks in antemortem, multimodal MRI from autopsy-confirmed cases to examine spreading pathology in sporadic frontotemporal lobar degeneration. We defined phases of progressive cortical atrophy on T1 -weighted MRI using a published algorithm in autopsied frontotemporal lobar degeneration with tau inclusions or with transactional DNA binding protein of ∼43 kDa inclusions...
2023: Brain communications
#24
JOURNAL ARTICLE
Laynie Dratch, Weiyi Mu, Elisabeth McCarty Wood, Brianna Morgan, Lauren Massimo, Cynthia Clyburn, Tanya Bardakjian, Murray Grossman, David J Irwin, Katheryn A Q Cousins
OBJECTIVE: There are limited studies exploring the support and education needs of individuals at-risk for or diagnosed with hereditary frontotemporal degeneration (FTD) and/or amyotrophic lateral sclerosis (ALS). This study evaluated a novel conference for this population to assess conference efficacy, probe how participants assessed relevant resources, and identify outstanding needs of persons at-risk/diagnosed. METHODS: We implemented a post-conference electronic survey that probed participants' satisfaction, prior experience with resources, and unmet needs...
December 2023: PEC Innov
#25
Sanjana Shellikeri, Sunghye Cho, Sharon Ash, Carmen Gonzalez-Recober, Corey T McMillan, Lauren Elman, Colin Quinn, Defne A Amado, Michael Baer, David J Irwin, Lauren Massimo, Chris Olm, Mark Liberman, Murray Grossman, Naomi Nevler
BACKGROUND AND OBJECTIVES: Patients with ALS-FTD spectrum disorders (ALS-FTSD) have mixed motor and cognitive impairments and require valid and quantitative assessment tools to support diagnosis and tracking of bulbar motor disease. This study aimed to validate a novel automated digital speech tool that analyzes vowel acoustics from natural, connected speech as a marker for impaired articulation due to bulbar motor disease in ALS-FTSD. METHODS: We used an automatic algorithm called Forced Alignment Vowel Extraction (FAVE) to detect spoken vowels and extract vowel acoustics from 1 minute audio-recorded picture descriptions...
May 1, 2023: medRxiv
#26
JOURNAL ARTICLE
Jack Carson Taylor, Hilary W Heuer, Annie L Clark, Amy B Wise, Masood Manoochehri, Leah Forsberg, Carly Mester, Meghana Rao, Daniell Brushaber, Joel Kramer, Ariane E Welch, John Kornak, Walter Kremers, Brian Appleby, Bradford C Dickerson, Kimiko Domoto-Reilly, Julie A Fields, Nupur Ghoshal, Neill Graff-Radford, Murray Grossman, Matthew Gh Hall, Edward D Huey, David Irwin, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Joseph C Masdeu, Mario F Mendez, Naomi Nevler, Chiadi U Onyike, Belen Pascual, Peter Pressman, Katherine P Rankin, Buddhika Ratnasiri, Julio C Rojas, Maria Carmela Tartaglia, Bonnie Wong, Maria Luisa Gorno-Tempini, Bradley F Boeve, Howard J Rosen, Adam L Boxer, Adam M Staffaroni
INTRODUCTION: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp). METHODS: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [ N = 101]; prodromal: 0...
2023: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
#27
Rebecca R Valentino, William J Scotton, Shanu F Roemer, Tammaryn Lashley, Michael G Heckman, Maryam Shoai, Alejandro Martinez-Carrasco, Nicole Tamvaka, Ronald L Walton, Matthew C Baker, Hannah L Macpherson, Raquel Real, Alexandra I Soto-Beasley, Kin Mok, Tamas Revesz, Thomas T Warner, Zane Jaunmuktane, Bradley F Boeve, Elizabeth A Christopher, Michael DeTure, Ranjan Duara, Neill R Graff-Radford, Keith A Josephs, David S Knopman, Shunsuke Koga, Melissa E Murray, Kelly E Lyons, Rajesh Pahwa, Joseph E Parisi, Ronald C Petersen, Jennifer Whitwell, Lea T Grinberg, Bruce Miller, Athena Schlereth, William W Seeley, Salvatore Spina, Murray Grossman, David J Irwin, Edward B Lee, EunRan Suh, John Q Trojanowski, Vivianna M Van Deerlin, David A Wolk, Theresa R Connors, Patrick M Dooley, Matthew P Frosch, Derek H Oakley, Iban Aldecoa, Mircea Balasa, Ellen Gelpi, Sergi Borrego-Écija, Rosa Maria de Eugenio Huélamo, Jordi Gascon-Bayarri, Raquel Sánchez-Valle, Pilar Sanz-Cartagena, Gerard Piñol-Ripoll, Laura Molina-Porcel, Eileen H Bigio, Margaret E Flanagan, Tamar Gefen, Emily J Rogalski, Sandra Weintraub, Javier Redding-Ochoa, Koping Chang, Juan C Troncoso, Stefan Prokop, Kathy L Newell, Bernardino Ghetti, Matthew Jones, Anna Richardson, Andrew C Robinson, Federico Roncaroli, Julie Snowden, Kieren Allinson, Oliver Green, James B Rowe, Poonam Singh, Thomas G Beach, Geidy E Serrano, Xena E Flowers, James E Goldman, Allison C Heaps, Sandra P Leskinen, Andrew F Teich, Sandra E Black, Julia L Keith, Mario Masellis, Istvan Bodi, Andrew King, Safa-Al Sarraj, Claire Troakes, Glenda M Halliday, John R Hodges, Jillian J Kril, John B Kwok, Olivier Piguet, Marla Gearing, Thomas Arzberger, Sigrun Roeber, Johannes Attems, Christopher M Morris, Alan J Thomas, Bret M Evers, Charles L White, Naguib Mechawar, Anne A Sieben, Patrick P Cras, Bart B De Vil, Peter Paul P P De Deyn, Charles Duyckaerts, Isabelle Le Ber, Danielle Seihean, Sabrina Turbant-Leclere, Ian R MacKenzie, Catriona McLean, Matthew D Cykowski, John F Ervin, Shih-Hsiu J Wang, Caroline Graff, Inger Nennesmo, Rashed M Nagra, James Riehl, Gabor G Kovacs, Giorgio Giaccone, Benedetta Nacmias, Manuela Neumann, Lee-Cyn Ang, Elizabeth C Finger, Cornelis Blauwendraat, Mike A Nalls, Andrew B Singleton, Dan Vitale, Cristina Cunha, Agostinho Carvalho, Zbigniew K Wszolek, Huw R Morris, Rosa Rademakers, John A Hardy, Dennis W Dickson, Jonathan D Rohrer, Owen A Ross
BACKGROUND: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the MAPT gene. The MAPT H2 haplotype has consistently been associated with a decreased disease risk of the 4-repeat tauopathies of progressive supranuclear palsy and corticobasal degeneration, however its role in susceptibility to PiD is unclear...
April 24, 2023: medRxiv
#28
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
May 10, 2023: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
#29
JOURNAL ARTICLE
Alexandra L Young, Jacob W Vogel, John L Robinson, Corey T McMillan, Rik Ossenkoppele, David A Wolk, David J Irwin, Lauren Elman, Murray Grossman, Virginia M-Y Lee, Edward B Lee, Oskar Hansson
TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterise TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use data-driven disease progression modelling to derive a fine-grained empirical staging system for the classification and differentiation of frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP, n=126), amyotrophic lateral sclerosis (ALS, n=141) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) with and without Alzheimer's disease (n=304)...
May 8, 2023: Brain
#30
Luke Harper, Sterre de Boer, Olof Lindberg, Jimmy Lätt, Nicholas Cullen, Lyles Clark, David Irwin, Lauren Massimo, Murray Grossman, Oskar Hansson, Yolande Pijnenburg, Corey T McMillan, Alexander F Santillo
BACKGROUND: Frontotemporal dementia is the second most common form of early onset dementia (< 65 years). Despite this there are few known disease modifying factors. The anterior cingulate is a focal point of pathology in behavioural variant frontotemporal dementia. Sulcation of the anterior cingulate is denoted by the presence of a paracingulate sulcus, a tertiary sulcus developing, where present during the third gestational trimester and remaining stable throughout life. This study aims to examine the impact of right paracingulate sulcal presence on the expression and prognosis of behavioural variant Frontotemporal Dementia...
March 31, 2023: medRxiv
#31
JOURNAL ARTICLE
Lawren VandeVrede, Renaud La Joie, Elisabeth H Thijssen, Breton M Asken, Stephanie A Vento, Torie Tsuei, Suzanne L Baker, Yann Cobigo, Corrina Fonseca, Hilary W Heuer, Joel H Kramer, Peter A Ljubenkov, Gil D Rabinovici, Julio C Rojas, Howie J Rosen, Adam M Staffaroni, Brad F Boeve, Brad C Dickerson, Murray Grossman, Edward D Huey, David J Irwin, Irene Litvan, Alexander Y Pantelyat, Maria Carmela Tartaglia, Jeffrey L Dage, Adam L Boxer
IMPORTANCE: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology...
May 1, 2023: JAMA Neurology
#32
JOURNAL ARTICLE
Katheryn A Q Cousins, David J Irwin, Alice Chen-Plotkin, Leslie M Shaw, Sanaz Arezoumandan, Edward B Lee, David A Wolk, Daniel Weintraub, Meredith Spindler, Andres Deik, Murray Grossman, Thomas F Tropea
OBJECTIVE: Within Lewy body spectrum disorders (LBSD) with α-synuclein pathology (αSyn), concomitant Alzheimer's disease (AD) pathology is common and is predictive of clinical outcomes, including cognitive impairment and decline. Plasma phosphorylated tau 181 (p-tau181 ) is sensitive to AD neuropathologic change (ADNC) in clinical AD, and plasma glial fibrillary acidic protein (GFAP) is associated with the presence of β-amyloid plaques. While these plasma biomarkers are well tested in clinical and pathological AD, their diagnostic and prognostic performance for concomitant AD in LBSD is unknown...
March 31, 2023: Annals of Clinical and Translational Neurology
#33
Emma Rhodes, Dawn Mechanic-Hamilton, Jeffrey S Phillips, Corey McMillan, Alejandra Bahena, Nykko Vitali, Quinn Hlava, Philip Cook, James Gee, Murray Grossman, Lauren Massimo
BACKGROUND: Assessment of personality change in Alzheimer's disease and related dementias (ADRD) is clinically meaningful but complicated by patient (i.e., reduced insight) and informant (i.e., caregiver burden) factors that confound accurate reporting of personality traits. This study assessed the impact of caregiver burden on informant report of Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness) and investigated regional cortical volumes associated with larger discrepancies in patient and informant report of Big Five personality traits...
March 13, 2023: medRxiv
#34
Lucia A A Giannini, Daniel T Ohm, Annemieke J M Rozemuller, Laynie Dratch, EunRan Suh, Vivianna M van Deerlin, John Q Trojanowski, Edward B Lee, John C van Swieten, Murray Grossman, Harro Seelaar, David J Irwin
No abstract text is available yet for this article.
May 2023: Acta Neuropathologica
#35
JOURNAL ARTICLE
Benjamin J Kim, Murray Grossman, Tomas S Aleman, Delu Song, Katheryn A Q Cousins, Corey T McMillan, Adrienne Saludades, Yinxi Yu, Edward B Lee, David Wolk, Vivianna M Van Deerlin, Leslie M Shaw, Gui-Shuang Ying, David J Irwin
While Alzheimer's disease (AD) is associated with inner retina thinning (retinal nerve fiber layer and ganglion cell layer), we have observed photoreceptor outer nuclear layer (ONL) thinning in patients with frontotemporal lobar degeneration tauopathy (FTLD-Tau) compared to normal controls. We hypothesized that ONL thinning may distinguish FTLD-Tau from patients with biomarker evidence of AD neuropathologic change (ADNC) and will correlate with FTLD-Tau disease severity. Predicted FTLD-Tau (pFTLD-Tau; n = 21; 33 eyes) and predicted ADNC (pADNC; n = 24; 46 eyes) patients were consecutively enrolled, underwent optical coherence tomography macula imaging, and disease was categorized (pFTLD-Tau vs...
February 1, 2023: Neurobiology of Aging
#36
Xueying Lyu, Michael Tran Duong, Long Xie, Robin de Flores, Hayley Richardson, Gyujoon Hwang, L E M Wisse, Michael DiCalogero, Corey T McMillan, John L Robinson, Sharon X Xie, Murray Grossman, Edward B Lee, David J Irwin, Bradford C Dickerson, Christos Davatzikos, Ilya M Nasrallah, Paul A Yushkevich, David A Wolk, Sandhitsu R Das
Variability in the relationship of tau-based neurofibrillary tangles (T) and degree of neurodegeneration (N) in Alzheimer's Disease (AD) is likely attributable to the non-specific nature of N, which is also modulated by such factors as other co-pathologies, age-related changes, and developmental differences. We studied this variability by partitioning patients within the Alzheimer's continuum into data-driven groups based on their regional T-N dissociation, which reflects the residuals after the effect of tau pathology is "removed"...
February 15, 2023: medRxiv
#37
Alexandra L Young, Jacob W Vogel, John L Robinson, Corey T McMillan, Rik Ossenkoppele, David A Wolk, David J Irwin, Lauren Elman, Murray Grossman, Virginia M-Y Lee, Edward B Lee, Oskar Hansson
TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterise TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use data-driven disease progression modelling to derive a fine-grained empirical staging system for the classification and differentiation of frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP, n=126), amyotrophic lateral sclerosis (ALS, n=141) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) with and without Alzheimer’s disease (n=304)...
February 2, 2023: medRxiv
#38
JOURNAL ARTICLE
Gianina Toller, Yann Cobigo, Patrick Callahan, Brian S Appleby, Danielle Brushaber, Kimiko Domoto-Reilly, Leah K Forsberg, Nupur Ghoshal, Jonathan Graff-Radford, Neil R Graff-Radford, Murray Grossman, Hilary W Heuer, John Kornak, Walter Kremers, Maria I Lapid, Gabriel Leger, Irene Litvan, Ian R Mackenzie, Maria B Pascual, Eliana M Ramos, Katya Rascovsky, Julio C Rojas, Adam M Staffaroni, Maria C Tartaglia, Arthur Toga, Sandra Weintraub, Zbigniew K Wszolek, Brad F Boeve, Adam L Boxer, Howard J Rosen, Katherine P Rankin
INTRODUCTION: Empathy relies on fronto-cingular and temporal networks that are selectively vulnerable in behavioral variant frontotemporal dementia (bvFTD). This study modeled when in the disease process empathy changes begin, and how they progress. METHODS: Four hundred thirty-one individuals with asymptomatic genetic FTD (n = 114), genetic and sporadic bvFTD (n = 317), and 163 asymptomatic non-carrier controls were enrolled. In sub-samples, we investigated empathy measured by the informant-based Interpersonal Reactivity Index (IRI) at each disease stage and over time (n = 91), and its correspondence to underlying atrophy (n = 51)...
January 2, 2023: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#39
JOURNAL ARTICLE
Thomas F Tropea, Teresa Waligorska, Sharon X Xie, Ilya M Nasrallah, Katheryn A Q Cousins, John Q Trojanowski, Murray Grossman, David J Irwin, Daniel Weintraub, Edward B Lee, David A Wolk, Alice S Chen-Plotkin, Leslie M Shaw
OBJECTIVE: To determine if plasma tau phosphorylated at threonine 181 (p-tau181) distinguishes pathology-confirmed Alzheimer's disease (AD) from normal cognition (NC) adults, to test if p-tau181 predicts cognitive and functional decline, and to validate findings in an external cohort. METHODS: Thirty-one neuropathology-confirmed AD cases, participants with clinical diagnoses of mild cognitive impairment (MCI, N = 91) or AD dementia (N = 64), and NC (N = 241) had plasma collected at study entry...
January 2023: Annals of Clinical and Translational Neurology
#40
JOURNAL ARTICLE
Peter T Nelson, Edward B Lee, Matthew D Cykowski, Irina Alafuzoff, Konstantinos Arfanakis, Johannes Attems, Carol Brayne, Maria M Corrada, Brittany N Dugger, Margaret E Flanagan, Bernardino Ghetti, Lea T Grinberg, Murray Grossman, Michel J Grothe, Glenda M Halliday, Masato Hasegawa, Suvi R K Hokkanen, Sally Hunter, Kurt Jellinger, Claudia H Kawas, C Dirk Keene, Naomi Kouri, Gabor G Kovacs, James B Leverenz, Caitlin S Latimer, Ian R Mackenzie, Qinwen Mao, Kirsty E McAleese, Richard Merrick, Thomas J Montine, Melissa E Murray, Liisa Myllykangas, Sukriti Nag, Janna H Neltner, Kathy L Newell, Robert A Rissman, Yuko Saito, S Ahmad Sajjadi, Katherine E Schwetye, Andrew F Teich, Dietmar R Thal, Sandra O Tomé, Juan C Troncoso, Shih-Hsiu J Wang, Charles L White, Thomas Wisniewski, Hyun-Sik Yang, Julie A Schneider, Dennis W Dickson, Manuela Neumann
An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data...
February 2023: Acta Neuropathologica
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