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JOURNAL ARTICLE
Sunghye Cho, Christopher A Olm, Sharon Ash, Sanjana Shellikeri, Galit Agmon, Katheryn A Q Cousins, David J Irwin, Murray Grossman, Mark Liberman, Naomi Nevler
INTRODUCTION: Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD). METHODS: We trained automatic classifiers with 99 speech features from 1 minute speech samples of 179 participants (ADNC = 36, FTLD = 60, healthy controls [HC] = 89)...
April 4, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Jeffrey S Phillips, Nagesh Adluru, Moo K Chung, Hamsanandini Radhakrishnan, Christopher A Olm, Philip A Cook, James C Gee, Katheryn A Q Cousins, Sanaz Arezoumandan, David A Wolk, Corey T McMillan, Murray Grossman, David J Irwin
INTRODUCTION: Multimodal evidence indicates Alzheimer's disease (AD) is characterized by early white matter (WM) changes that precede overt cognitive impairment. WM changes have overwhelmingly been investigated in typical, amnestic mild cognitive impairment and AD; fewer studies have addressed WM change in atypical, non-amnestic syndromes. We hypothesized each non-amnestic AD syndrome would exhibit WM differences from amnestic and other non-amnestic syndromes. MATERIALS AND METHODS: Participants included 45 cognitively normal (CN) individuals; 41 amnestic AD patients; and 67 patients with non-amnestic AD syndromes including logopenic-variant primary progressive aphasia (lvPPA, n = 32), posterior cortical atrophy (PCA, n = 17), behavioral variant AD (bvAD, n = 10), and corticobasal syndrome (CBS, n = 8)...
2024: Frontiers in Neuroscience
#3
JOURNAL ARTICLE
Adam M Staffaroni, Annie L Clark, Jack C Taylor, Hilary W Heuer, Mark Sanderson-Cimino, Amy B Wise, Sreya Dhanam, Yann Cobigo, Amy Wolf, Masood Manoochehri, Leah Forsberg, Carly Mester, Katherine P Rankin, Brian S Appleby, Ece Bayram, Andrea Bozoki, David Clark, R Ryan Darby, Kimiko Domoto-Reilly, Julie A Fields, Douglas Galasko, Daniel Geschwind, Nupur Ghoshal, Neill Graff-Radford, Murray Grossman, Ging-Yuek Hsiung, Edward D Huey, David T Jones, Maria I Lapid, Irene Litvan, Joseph C Masdeu, Lauren Massimo, Mario F Mendez, Toji Miyagawa, Belen Pascual, Peter Pressman, Vijay K Ramanan, Eliana Marisa Ramos, Katya Rascovsky, Erik D Roberson, M Carmela Tartaglia, Bonnie Wong, Bruce L Miller, John Kornak, Walter Kremers, Jason Hassenstab, Joel H Kramer, Bradley F Boeve, Howard J Rosen, Adam L Boxer
IMPORTANCE: Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD. OBJECTIVE: To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations...
April 1, 2024: JAMA Network Open
#4
JOURNAL ARTICLE
Frederike C Oertel, Daniel Casillas, Yann Cobigo, Shivany Condor Montes, Hilary W Heuer, Makenna Chapman, Alexandra Beaudry-Richard, Henriette Reinsberg, Ahmed Abdelhak, Christian Cordano, Bradley F Boeve, Bradford C Dickerson, Murray Grossman, Edward Huey, David J Irwin, Irene Litvan, Alexander Pantelyat, M Carmela Tartaglia, Lawren Vandevrede, Adam Boxer, Ari J Green
No abstract text is available yet for this article.
February 3, 2024: Acta Neuropathologica
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JOURNAL ARTICLE
Matthew Clark, Christopher Meyer, Jaime Ramos-Cejudo, Danne C Elbers, Karen Pierce-Murray, Rafael Fricks, Gil Alterovitz, Luigi Rao, Mary T Brophy, Nhan V Do, Robert L Grossman, Nathanael R Fillmore
High-resolution whole slide image scans of histopathology slides have been widely used in recent years for prediction in cancer. However, in some cases, clinical informatics practitioners may only have access to low-resolution snapshots of histopathology slides, not high-resolution scans. We evaluated strategies for training neural network prognostic models in non-small cell lung cancer (NSCLC) based on low-resolution snapshots, using data from the Veterans Affairs Precision Oncology Data Repository. We compared strategies without transfer learning, with transfer learning from general domain images, and with transfer learning from publicly available high-resolution histopathology scans...
January 25, 2024: Studies in Health Technology and Informatics
#6
JOURNAL ARTICLE
Sanaz Arezoumandan, Katheryn A Q Cousins, Daniel T Ohm, MaKayla Lowe, Min Chen, James Gee, Jeffrey S Phillips, Corey T McMillan, Kelvin C Luk, Andres Deik, Meredith A Spindler, Thomas F Tropea, Daniel Weintraub, David A Wolk, Murray Grossman, Virginia Lee, Alice S Chen-Plotkin, Edward B Lee, David J Irwin
OBJECTIVE: Alzheimer's disease neuropathologic change and alpha-synucleinopathy commonly co-exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta-amyloid compared to alpha-synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia...
January 23, 2024: Annals of Clinical and Translational Neurology
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JOURNAL ARTICLE
Galit Agmon, Sameer Pradhan, Sharon Ash, Naomi Nevler, Mark Liberman, Murray Grossman, Sunghye Cho
PURPOSE: Multiple methods have been suggested for quantifying syntactic complexity in speech. We compared eight automated syntactic complexity metrics to determine which best captured verified syntactic differences between old and young adults. METHOD: We used natural speech samples produced in a picture description task by younger ( n = 76, ages 18-22 years) and older ( n = 36, ages 53-89 years) healthy participants, manually transcribed and segmented into sentences...
January 12, 2024: Journal of Speech, Language, and Hearing Research: JSLHR
#8
JOURNAL ARTICLE
Naomi Nevler, Sunghye Cho, Katheryn A Q Cousins, Sharon Ash, Christopher A Olm, Sanjana Shellikeri, Galit Agmon, Carmen Gonzalez-Recober, Sharon X Xie, Megan S Barker, Masood Manoochehri, Corey T Mcmillan, David J Irwin, Lauren Massimo, Laynie Dratch, Gayathri Cheran, Edward D Huey, Stephanie A Cosentino, Vivianna M Van Deerlin, Mark Y Liberman, Murray Grossman
BACKGROUND AND OBJECTIVES: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic. METHODS: In this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020...
January 23, 2024: Neurology
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JOURNAL ARTICLE
Ting Shen, Jacob W Vogel, Jeffrey Duda, Jeffrey S Phillips, Philip A Cook, James Gee, Lauren Elman, Colin Quinn, Defne A Amado, Michael Baer, Lauren Massimo, Murray Grossman, David J Irwin, Corey T McMillan
BACKGROUND: TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum...
December 7, 2023: Translational Neurodegeneration
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JOURNAL ARTICLE
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, Christopher A Olm, Mark Y Liberman, Murray Grossman, Naomi Nevler
OBJECTIVE: To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD). METHODS: Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9...
December 5, 2023: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
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JOURNAL ARTICLE
Jeffrey S Phillips, John L Robinson, Katheryn A Q Cousins, David A Wolk, Edward B Lee, Corey T McMillan, John Q Trojanowski, Murray Grossman, David J Irwin
Mixed pathologies are common in neurodegenerative disease; however, antemortem imaging rarely captures copathologic effects on brain atrophy due to a lack of validated biomarkers for non-Alzheimer's pathologies. We leveraged a dataset comprising antemortem MRI and postmortem histopathology to assess polypathologic associations with atrophy in a clinically heterogeneous sample of 125 human dementia patients (41 female, 84 male) with T1-weighted MRI ≤ 5 years before death and postmortem ordinal ratings of amyloid- β , tau, TDP-43, and α -synuclein...
November 22, 2023: Journal of Neuroscience
#12
JOURNAL ARTICLE
Ganna Blazhenets, David N Soleimani-Meigooni, Wesley Thomas, Nidhi Mundada, Matthias Brendel, Stephanie Vento, Lawren VandeVrede, Hilary W Heuer, Peter Ljubenkov, Julio C Rojas, Miranda K Chen, Alinda N Amuiri, Zachary Miller, Maria L Gorno-Tempini, Bruce L Miller, Howie J Rosen, Irene Litvan, Murray Grossman, Brad Boeve, Alexander Pantelyat, Maria Carmela Tartaglia, David J Irwin, Brad C Dickerson, Suzanne L Baker, Adam L Boxer, Gil D Rabinovici, Renaud La Joie
Tau PET has enabled the visualization of paired helical filaments of 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18 F]fluoro)pyridin-4-yl)-9 H -pyrrolo[2,3-b:4,5c']dipyridine ([18 F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images...
December 1, 2023: Journal of Nuclear Medicine
#13
JOURNAL ARTICLE
Carmen Gonzalez-Recober, Naomi Nevler, Sanjana Shellikeri, Katheryn A Q Cousins, Emma Rhodes, Mark Liberman, Murray Grossman, David Irwin, Sunghye Cho
INTRODUCTION: Category and letter fluency tasks are commonly used neuropsychological tasks to evaluate lexical retrieval. METHODS: This study used validated automated methods, which allow for more expansive investigation, to analyze speech production of both category ("Animal") and letter ("F") fluency tasks produced by healthy participants ( n = 36) on an online platform. Recordings were transcribed and analyzed through automated pipelines, which utilized natural language processing and automatic acoustic processing tools...
2023: Frontiers in Psychology
#14
JOURNAL ARTICLE
Daniel T Ohm, Emma Rhodes, Alejandra Bahena, Noah Capp, MaKayla Lowe, Philip Sabatini, Winifred Trotman, Christopher A Olm, Jeffrey Phillips, Karthik Prabhakaran, Katya Rascovsky, Lauren Massimo, Corey McMillan, James Gee, M Dylan Tisdall, Paul A Yushkevich, Edward B Lee, Murray Grossman, David J Irwin
Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively...
2023: Frontiers in Neurology
#15
JOURNAL ARTICLE
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
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...
2023: Brain communications
#16
JOURNAL ARTICLE
Emma Rhodes, Dawn Mechanic-Hamilton, Jeffrey S Phillips, Alejandra Bahena, Nykko Vitali, Quinn Hlava, Philip Cook, James Gee, Murray Grossman, Corey McMillan, Lauren Massimo
OBJECTIVE: Personality change in Alzheimer's disease and related dementias (ADRD) is complicated by the patient and informant factors that confound accurate reporting of personality traits. We assessed the impact of caregiver burden on informant report of Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness) and investigated the regional cortical volumes associated with larger discrepancies in the patient and informant report of the Big Five personality traits...
October 20, 2023: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
#17
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
June 1, 2023: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
#18
Ting Shen, Jacob W Vogel, Jeffrey Duda, Jeffrey S Phillips, Philip A Cook, James Gee, Lauren Elman, Colin Quinn, Defne A Amado, Michael Baer, Lauren Massimo, Murray Grossman, David J Irwin, Corey T McMillan
Background TDP-43 proteinopathies represents a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum. Methods We used a data-driven procedure to identify 13 anatomic clusters of brain volumes for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43...
August 10, 2023: Research Square
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REVIEW
Murray Grossman, William W Seeley, Adam L Boxer, Argye E Hillis, David S Knopman, Peter A Ljubenov, Bruce Miller, Olivier Piguet, Rosa Rademakers, Jennifer L Whitwell, Henrik Zetterberg, John C van Swieten
Frontotemporal lobar degeneration (FTLD) is one of the most common causes of early-onset dementia and presents with early social-emotional-behavioural and/or language changes that can be accompanied by a pyramidal or extrapyramidal motor disorder. About 20-25% of individuals with FTLD are estimated to carry a mutation associated with a specific FTLD pathology. The discovery of these mutations has led to important advances in potentially disease-modifying treatments that aim to slow progression or delay disease onset and has improved understanding of brain functioning...
August 10, 2023: Nature Reviews. Disease Primers
#20
JOURNAL ARTICLE
Liwen Zhang, Taru M Flagan, Suvi Häkkinen, Stephanie A Chu, Jesse A Brown, Alex J Lee, Lorenzo Pasquini, Maria Luisa Mandelli, Maria Luisa Gorno-Tempini, Virginia E Sturm, Jennifer S Yokoyama, Brian S Appleby, Yann Cobigo, Bradford C Dickerson, Kimiko Domoto-Reilly, Daniel H Geschwind, Nupur Ghoshal, Neill R Graff-Radford, Murray Grossman, Ging-Yuek Robin Hsiung, Edward D Huey, Kejal Kantarci, Argentina Lario Lago, Irene Litvan, Ian R Mackenzie, Mario F Mendez, Chiadi U Onyike, Eliana Marisa Ramos, Erik D Roberson, Maria Carmela Tartaglia, Arthur W Toga, Sandra Weintraub, Zbigniew K Wszolek, Leah K Forsberg, Hilary W Heuer, Bradley F Boeve, Adam L Boxer, Howard J Rosen, Bruce L Miller, William W Seeley, Suzee E Lee
OBJECTIVE: Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers. METHODS: We compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses...
October 2023: Annals of Neurology
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