34 results on '"Josephs, K.A."'
Search Results
2. Focal Cortical Degenerations
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Josephs, K.A., primary
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- 2015
- Full Text
- View/download PDF
3. Corticobasal Degeneration
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Jung, Y., primary and Josephs, K.A., additional
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- 2015
- Full Text
- View/download PDF
4. Video-tutorial for the Movement Disorder Society criteria for progressive supranuclear palsy
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Iankova, V. Respondek, G. Saranza, G. Painous, C. Cámara, A. Compta, Y. Aiba, I. Balint, B. Giagkou, N. Josephs, K.A. Otsuki, M. Golbe, L.I. Bhatia, K.P. Stamelou, M. Lang, A.E. Höglinger, G.U. for the Movement Disorder Society-endorsed PSP Study Group
- Abstract
Background: The International Parkinson and Movement Disorder Society-endorsed Progressive Supranuclear Palsy Study Group published clinical diagnostic criteria for progressive supranuclear palsy in 2017, aiming to optimize early, sensitive and specific diagnosis. Objective: To assist physicians in the application of these criteria, we developed a video-based tutorial in which all core clinical features and clinical clues are depicted and explained. Methods: Patients provided written informed consent to the publication of their videos. High-quality videos along with essential descriptions were collected by the study group members. Most educational videos were selected in a structured consensus process. Results: We provide 68 videos of all core clinical features and clinical clues defined by the diagnostic criteria, along with instructive descriptions of the depicted patients, examination techniques and clinical findings. Conclusions: This comprehensive video-based tutorial will support physicians in the application of the diagnostic criteria of progressive supranuclear palsy. © 2020
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- 2020
5. The (alpha)-synuclein gene in multiple system atrophy
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Ozawa, T., Healy, D.G., Abou-Sleiman, P.M., Ahmadi, K.R., Quinn, N., Lees, A.J., Shaw, K., Wullner, U., Berciano, J., Moller, J.C., Kamm, C., Burk, K., Josephs, K.A., Barone, P., Tolosa, E., Goldstein, D.B., Wenning, G., Geser, F., Holton, J.L., Gasser, T., Revesz, T., and Wood, N.W.
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Atrophy -- Genetic aspects ,Atrophy -- Development and progression ,Gene expression -- Research ,Health ,Psychology and mental health - Published
- 2006
6. Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration
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Janssen, J.C., Schott, J.M., Cipolotti, L., Fox, N.C., Scahill, R.I., Josephs, K.A., Stevens, J.M., and Rossor, M.N.
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Temporal lobes -- Diseases ,Temporal lobes -- Genetic aspects ,Familial diseases -- Research ,Degeneration (Pathology) -- Patient outcomes ,Atrophy -- Diagnosis ,Atrophy -- Development and progression ,Magnetic resonance imaging ,Brain mapping ,Health ,Psychology and mental health - Published
- 2005
7. How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy
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Grimm, M.-J. Respondek, G. Stamelou, M. Arzberger, T. Ferguson, L. Gelpi, E. Giese, A. Grossman, M. Irwin, D.J. Pantelyat, A. Rajput, A. Roeber, S. van Swieten, J.C. Troakes, C. Antonini, A. Bhatia, K.P. Colosimo, C. van Eimeren, T. Kassubek, J. Levin, J. Meissner, W.G. Nilsson, C. Oertel, W.H. Piot, I. Poewe, W. Wenning, G.K. Boxer, A. Golbe, L.I. Josephs, K.A. Litvan, I. Morris, H.R. Whitwell, J.L. Compta, Y. Corvol, J.-C. Lang, A.E. Rowe, J.B. Höglinger, G.U. for the Movement Disorder Society-endorsed PSP Study Group
- Abstract
Background: The Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them. Methods: We retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations. Results: Comprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1. Conclusions: The proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society. © 2019 International Parkinson and Movement Disorder Society
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- 2019
8. Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
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Bonham, L.W., Steele, N.Z.R., Karch, C.M., Broce, I., Geier, E.G., Wen, N.L., Momeni, P., Hardy, J., Miller, Z.A., Gorno-Tempini, M.L., Hess, C.P., Lewis, P., Miller, B.L., Seeley, W.W., Manzoni, C., Desikan, R.S., Baranzini, S.E., Ferrari, R., Yokoyama, J.S., Hernandez, D.G., Nalls, M.A., Rohrer, J.D., Ramasamy, A., Kwok, J.B.J., Dobson-Stone, C., Schofield, P.R., Halliday, G.M., Hodges, J.R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, Isabel, Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N.J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, Diego, Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Clarimón, J., Lleó, Alberto, Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I.R.A., Hsiung, G.Y.R., Mann, D.M.A., Grafman, J., Morris, C.M., Attems, J., Griffiths, T.D., McKeith, I.G., Thomas, A.J., Pietrini, P., Huey, E.D., Wassermann, E.M., Baborie, A., Jaros, E., Tierney, M.C., Pastor, Pau, Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J.B., Schlachetzki, J.C.M., Uphill, J., Collinge, J., Mead, S., Danek, A., Van Deerlin, V.M., Grossman, M., Trojanowski, J.Q., van der Zee, J., Cruts, M., Van Broeckhoven, C., Cappa, S.F., Leber, I., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, Sandro, Bagnoli, S., Piaceri, I., Nielsen, J.E., Hjermind, L.E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M.N., Fox, N.C., Warren, J.D., Spillantini, M.G., Morris, H.R., Rizzu, P., Heutink, P., Snowden, J.S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A.C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M.E., Smirne, N., Rademakers, R., Baker, M., Dickson, Dennis W., Graff-Radford, N.R., Petersen, R.C., Knopman, D., Josephs, K.A., Boeve, B.F., Parisi, J.E., Karydas, A.M., Rosen, H., van Swieten, J.C., Dopper, E.G.P., Seelaar, H., Pijnenburg, Y.A.L., Scheltens, Philip, Logroscino, G., Capozzo, R., Novelli, V., Puca, A.A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H.H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A.B., Universitat Autònoma de Barcelona, Broce, Iris [0000-0003-4932-1430], Miller, Zachary A. [0000-0002-5991-3053], Lewis, Patrick [0000-0003-4537-0489], Baranzini, Sergio E. [0000-0003-0067-194X], Apollo - University of Cambridge Repository, Int FTD-Genomics Consortium, Neurology, Amsterdam Neuroscience - Neurodegeneration, Divisions, and CCA - Imaging and biomarkers
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0301 basic medicine ,Aging ,Transcription, Genetic ,Gene regulatory network ,lcsh:Medicine ,Genome-wide association study ,Apoptosis ,Neurodegenerative ,Primary progressive aphasia ,Cohort Studies ,0302 clinical medicine ,692/617/375/132 ,Risk Factors ,Databases, Genetic ,2.1 Biological and endogenous factors ,Gene Regulatory Networks ,Protein Interaction Maps ,Aetiology ,lcsh:Science ,Multidisciplinary ,Neurodegeneration ,Neurodegenerative diseases ,article ,Frontotemporal lobar degeneration ,631/208/205 ,Single Nucleotide ,Phenotype ,ddc ,3. Good health ,DNA-Binding Proteins ,Frontotemporal Dementia (FTD) ,692/617/375/365 ,Neurological ,Medical genetics ,38/39 ,Engineering sciences. Technology ,Transcription ,Biotechnology ,medicine.medical_specialty ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Databases ,Rare Diseases ,Genetic ,medicine ,Aphasia ,Acquired Cognitive Impairment ,Genetics ,Humans ,Primary Progressive Nonfluent Aphasia ,Polymorphism ,Gene ,Genetic association study ,International FTD-Genomics Consortium ,lcsh:R ,Human Genome ,Neurosciences ,medicine.disease ,Brain Disorders ,631/208/199 ,030104 developmental biology ,Gene Expression Regulation ,RNA ,lcsh:Q ,Dementia ,Gene expression ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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- 2019
9. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria
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Höglinger, G.U. Respondek, G. Stamelou, M. Kurz, C. Josephs, K.A. Lang, A.E. Mollenhauer, B. Müller, U. Nilsson, C. Whitwell, J.L. Arzberger, T. Englund, E. Gelpi, E. Giese, A. Irwin, D.J. Meissner, W.G. Pantelyat, A. Rajput, A. van Swieten, J.C. Troakes, C. Antonini, A. Bhatia, K.P. Bordelon, Y. Compta, Y. Corvol, J.-C. Colosimo, C. Dickson, D.W. Dodel, R. Ferguson, L. Grossman, M. Kassubek, J. Krismer, F. Levin, J. Lorenzl, S. Morris, H.R. Nestor, P. Oertel, W.H. Poewe, W. Rabinovici, G. Rowe, J.B. Schellenberg, G.D. Seppi, K. van Eimeren, T. Wenning, G.K. Boxer, A.L. Golbe, L.I. Litvan, I. Wenning, G.K. Höglinger, G.U. Morris, H.R. Litvan, I. Kassubek, J. Corvol, J.-C. Whitwell, J.L. Levin, J. van Swieten, J. Bhatia, K.P. Josephs, K.A. Seppi, K. Golbe, L.I. Grossman, M. Dodel, R. Lorenzl, S. van Eimeren, T. Arzberger, T. Müller, U. Poewe, W. Oertel, W.H. Compta, Y. Bordelon, Y. the Movement Disorder Society-endorsed PSP Study Group
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eye diseases - Abstract
Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society
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- 2017
10. Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be?
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Whitwell, J.L. Höglinger, G.U. Antonini, A. Bordelon, Y. Boxer, A.L. Colosimo, C. van Eimeren, T. Golbe, L.I. Kassubek, J. Kurz, C. Litvan, I. Pantelyat, A. Rabinovici, G. Respondek, G. Rominger, A. Rowe, J.B. Stamelou, M. Josephs, K.A. for the Movement Disorder Society-endorsed PSP Study Group
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eye diseases - Abstract
PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five-level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group-level findings, level 2 representing biomarkers with demonstrable individual-level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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- 2017
11. Which ante mortem clinical features predict progressive supranuclear palsy pathology?
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Respondek, G. Kurz, C. Arzberger, T. Compta, Y. Englund, E. Ferguson, L.W. Gelpi, E. Giese, A. Irwin, D.J. Meissner, W.G. Nilsson, C. Pantelyat, A. Rajput, A. van Swieten, J.C. Troakes, C. Josephs, K.A. Lang, A.E. Mollenhauer, B. Müller, U. Whitwell, J.L. Antonini, A. Bhatia, K.P. Bordelon, Y. Corvol, J.-C. Colosimo, C. Dodel, R. Grossman, M. Kassubek, J. Krismer, F. Levin, J. Lorenzl, S. Morris, H. Nestor, P. Oertel, W.H. Rabinovici, G.D. Rowe, J.B. van Eimeren, T. Wenning, G.K. Boxer, A. Golbe, L.I. Litvan, I. Stamelou, M. Höglinger, G.U. for the Movement Disorder Society-Endorsed PSP Study Group
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eye diseases - Abstract
Background: Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. Objective: To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. Methods: We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Results: Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Conclusions: Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society
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- 2017
12. Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy
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Stamelou, M. Schöpe, J. Wagenpfeil, S. Del Ser, T. Bang, J. Lobach, I.Y. Luong, P. Respondek, G. Oertel, W.H. Boxer, A. Höglinger, G.U. Williams, D. Lafontaine, A.L. Marras, C. Jog, M. Panisset, M. Lang, A. Parker, L. Stewart, A.J. Corvol, J.-C. Azulay, J.-P. Couratier, P. Mollenhauer, B. Lorenzl, S. Ludolph, A. Benecke, R. Hoglinger, G. Lipp, A. Reichmann, H. Woitalla, D. Chan, D. Zermansky, A. Burn, D.J. Lees, A. Boxer, A. Miller, B.L. Lobach, I.V. Roberson, E. Honig, L. Zamrini, E. Pahwa, R. Bordelon, Y. Driver-Dunkley, E. Lessig, S. Lew, M. Womack, K. Boeve, B. Ferrara, J. Hillis, A. Kaufer, D. Kumar, R. Xie, T. Gunzler, S. Zesiewicz, T. Dayalu, P. Golbe, L. Grossman, M. Jankovic, J. McGinnis, S. Santiago, A. Tuite, P. Isaacson, S. Leegwater-Kim, J. Litvan, I. Grossman, M. Knopman, D.S. Schneider, L.S. Doody, R.S. Golbe, L. Koestler, M. Jack, C.R. Van Deerlin, V. Randolph, C. Gozes, I. Whitaker, S. Hirman, J. Gold, M. Morimoto, B.H. Gómez, J.C. Tijero, B. Berganzo, K. García de Yebenes, J. Lopez Sendón, J.L. Garcia, G. Tolosa, E. Buongiorno, M.T. Bargalló, N. Burguera, J.A. Martinez, I. Ruiz-Martínez, 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. Hoglinger, G. Hollerhage, M. Reichmann, H. Wolz, M. Schneider, C. Klingelhofer, L. Berg, D. Maetzler, W. Srulijes, K.K. Ludolph, A. Kassubek, J. Steiger, M. Tyler, K. 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. Bhatia, K. Bordelon, Y.M. Colosimo, C. Dodel, R. Josephs, K.A. Morris, H. Mueller, U. Paviour, D. Schellenberg, G. Steele, J. van Swieten, J.C. Whitwell, J. Tau Restoration on PSP (TAUROS) Investigators The MDS-Endorsed PSP Study Group
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eye diseases - Abstract
Background: Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. Methods: We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. Results: The total PSP-Rating Scale required the least number of patients per group (N=51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. Conclusions: We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome. © 2016 International Parkinson and Movement Disorder Society.
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- 2016
13. Survival profiles of patients with frontotemporal dementia and motor neuron disease
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Hu, W.T., Seelaar, H., Josephs, K.A., Knopman, D.S., Boeve, B.F., Sorenson, E.J., McCluskey, L., Elman, L., Schelhaas, H.J., Parisi, J.E., Kuesters, B., Lee, V.M., Trojanowski, J.Q., Petersen, R.C., Swieten, J.C. van, and Grossman, M.
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Perception and Action [DCN 1] ,Alzheimer Centre [NCEBP 11] ,Functional Neurogenomics [DCN 2] - Abstract
Contains fulltext : 81426.pdf (Publisher’s version ) (Closed access) BACKGROUND: Frontotemporal dementia and amyotrophic lateral sclerosis are neurodegenerative diseases associated with TAR DNA-binding protein 43- and ubiquitin-immunoreactive pathologic lesions. OBJECTIVE: To determine whether survival is influenced by symptom of onset in patients with frontotemporal dementia and amyotrophic lateral sclerosis. DESIGN, SETTING, AND PATIENTS: Retrospective review of patients with both cognitive impairment and motor neuron disease consecutively evaluated at 4 academic medical centers in 2 countries. MAIN OUTCOME MEASURES: Clinical phenotypes and survival patterns of patients. RESULTS: A total of 87 patients were identified, including 60 who developed cognitive symptoms first, 19 who developed motor symptoms first, and 8 who had simultaneous onset of cognitive and motor symptoms. Among the 59 deceased patients, we identified 2 distinct subgroups of patients according to survival. Long-term survivors had cognitive onset and delayed emergence of motor symptoms after a long monosymptomatic phase and had significantly longer survival than the typical survivors (mean, 67.5 months vs 28.2 months, respectively; P < .001). Typical survivors can have simultaneous or discrete onset of cognitive and motor symptoms, and the simultaneous-onset patients had shorter survival (mean, 19.2 months) than those with distinct cognitive or motor onset (mean, 28.6 months) (P = .005). CONCLUSIONS: Distinct patterns of survival profiles exist in patients with frontotemporal dementia and motor neuron disease, and overall survival may depend on the relative timing of the emergence of secondary symptoms.
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- 2009
14. Frontotemporal brain sagging syndrome: an SIH-like presentation mimicking FTD
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Wicklund, M.R., Mokri, B., Drubach, D.A., Boeve, B.F., Parisi, J.E., and Josephs, K.A.
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Aged, 80 and over ,Diagnostic Imaging ,Male ,Intracranial Hypotension ,Articles ,Middle Aged ,Neuropsychological Tests ,Magnetic Resonance Imaging ,Methylprednisolone ,Temporal Lobe ,Frontal Lobe ,Radiography ,Neuroprotective Agents ,Frontotemporal Dementia ,Humans ,Female ,Cognition Disorders ,Radionuclide Imaging ,Aged ,Follow-Up Studies ,Retrospective Studies - Abstract
Behavioral variant frontotemporal dementia (bvFTD) is a relatively well-defined clinical syndrome. It is associated with frontal and temporal lobe structural/metabolic changes and pathologic findings of a neurodegenerative disease. We have been evaluating patients with clinical and imaging features partially consistent with bvFTD but with evidence also suggestive of brain sagging, which we refer to as frontotemporal brain sagging syndrome (FBSS).Retrospective medical chart review to identify all patients seen at our institution between 1996 and 2010, who had a clinical diagnosis of FTD and imaging evidence of brain sag.Eight patients, 7 male and 1 female, were diagnosed with FBSS. The median age at symptom onset was 53 years. All patients had insidious onset and slow progression of behavioral and cognitive dysfunction accompanied by daytime somnolence and headache. Of the 5 patients with functional imaging, all showed evidence of hypometabolism of the frontotemporal regions. On brain MRI, all patients had evidence of brain sagging with distortion of the brainstem; 3 patients had diffuse pachymeningeal enhancement. CSF opening pressure was varied and CSF protein was mildly elevated. A definite site of CSF leak was not identified by myelogram or cisternography, except in one patient with a site highly suggestive of leak who subsequently underwent surgery confirming a CSF leak. In 2 patients with a neuropathologic examination, there was no evidence of a neurodegenerative disease.This case series demonstrates that FBSS may mimic typical bvFTD but should be recognized as an unusual presentation that is potentially treatable.
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- 2011
15. Adult onset Niemann-Pick disease type C presenting with psychosis. (Shot Report)
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Josephs, K.A., Van Gerpen, M.W., and Van Gerpen, J.A.
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Patients -- Care and treatment ,Niemann-Pick disease -- Research -- Care and treatment ,Health ,Psychology and mental health ,Care and treatment ,Research ,Methods - Abstract
Niemann-Pick disease type C (NPC) is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders (ataxia, chorea, dystonia, and myoclonus), [...]
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- 2003
16. Neurofilament inclusion body disease: a new proteinopathy?
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Josephs, K.A., Holton, J.L., Rossor, M.N., Braendgaard, H., Ozawa, T., Fox, N.C., Petersen, R.C., Pearl, G.S., Ganguly, M., Rosa, P., Laursen, H., Parisi, J.E., Waldemar, G., Quinn, N.P., Dickson, D.W., and Revesz, T.
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- 2003
17. Corrigendum to “Dopamine agonist-triggered pathological behaviors: Surveillance in the PD clinic reveals high frequencies” [Parkinsonism Relat Disord 17 (2011) 260–264]
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Hassan, A., primary, Bower, J.H., additional, Kumar, N., additional, Matsumoto, J.Y., additional, Fealey, R.D., additional, Josephs, K.A., additional, and Ahlskog, J.E., additional
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- 2011
- Full Text
- View/download PDF
18. O.014 Neuropathology of non-motor features of Parkinson disease
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Dickson, D.W., primary, Fujishiro, H., additional, Orr, C., additional, DelleDonne, A., additional, Josephs, K.A., additional, Frigerio, R., additional, Burnett, M., additional, Parisi, J.E., additional, Klos, K.J., additional, and Ahlskog, J.E., additional
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- 2009
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19. P1.204 Combined resting–postural tremor – a variant of essential tremor
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Ahlskog, M.C., primary, Josephs, K.A., additional, Bower, J.H., additional, and Ahlskog, J.E., additional
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- 2009
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20. Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia
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Josephs, K.A., primary, Boeve, B.F., additional, Duffy, J.R., additional, Smith, G.E., additional, Knopman, D.S., additional, Parisi, J.E., additional, Petersen, R.C., additional, and Dickson, D.W., additional
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- 2005
- Full Text
- View/download PDF
21. Late-onset frontotemporal dementia associated with progressive supranuclear palsy/argyrophilic grain disease/Alzheimer’s disease pathology
- Author
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Rippon, G.A., primary, Boeve, B.F., additional, Parisi, J.E., additional, Dickson, D.W., additional, Ivnik, R.I., additional, Jack, C.R., additional, Hutton, M., additional, Baker, M., additional, Josephs, K.A., additional, Knopman, D.S., additional, and Petersen, R.C., additional
- Published
- 2005
- Full Text
- View/download PDF
22. Pathologically confirmed corticobasal degeneration presenting with visuospatial dysfunction
- Author
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Tang-Wai, D.F., primary, Josephs, K.A., additional, Boeve, B.F., additional, Dickson, D.W., additional, Parisi, J.E., additional, and Petersen, R.C., additional
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- 2003
- Full Text
- View/download PDF
23. Long-term cognitive outcomes following out-of-hospital cardiac arrest
- Author
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Mateen, F.J., Josephs, K.A., Trenerry, M.R., Felmlee-Devine, M.D., Weaver, A.L., Carone, M., and White, R.D.
- Abstract
To report the neurologic outcomes in long-term survivors of out-of-hospital cardiac arrest with ventricular fibrillation as the presenting rhythm (OHCA VF) at a population level.
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- 2011
- Full Text
- View/download PDF
24. Altered functional connectivity in asymptomatic MAPTsubjects
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Whitwell, J.L., Josephs, K.A., Avula, R., Tosakulwong, N., Weigand, S.D., Senjem, M.L., Vemuri, P., Jones, D.T., Gunter, J.L., Baker, M., Wszolek, Z.K., Knopman, D.S., Rademakers, R., Petersen, R.C., Boeve, B.F., and Jack, C.R.
- Abstract
To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD).
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- 2011
- Full Text
- View/download PDF
25. Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPTor GRN
- Author
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Whitwell, J.L., Weigand, S.D., Gunter, J.L., Boeve, B.F., Rademakers, R., Baker, M., Knopman, D.S., Wszolek, Z.K., Petersen, R.C., Jack, C.R., and Josephs, K.A.
- Abstract
To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations.
- Published
- 2011
- Full Text
- View/download PDF
26. Predicting survival in frontotemporal dementia with motor neuron disease(Podcast)
- Author
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Coon, E.A., Sorenson, E.J., Whitwell, J.L., Knopman, D.S., and Josephs, K.A.
- Abstract
To determine whether clinical and demographic features are associated with prognosis in patients with frontotemporal dementia and motor neuron disease (FTD-MND).
- Published
- 2011
- Full Text
- View/download PDF
27. Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?
- Author
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Whitwell, J.L., Jack, C.R., Parisi, J.E., Senjem, M.L., Knopman, D.S., Boeve, B.F., Rademakers, R., Baker, M., Petersen, R.C., Dickson, D.W., and Josephs, K.A.
- Abstract
To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD).
- Published
- 2010
- Full Text
- View/download PDF
28. Imaging correlates of pathology in corticobasal syndrome(Podcast)
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Whitwell, J.L., Jack, C.R., Boeve, B.F., Parisi, J.E., Ahlskog, J.E., Drubach, D.A., Senjem, M.L., Knopman, D.S., Petersen, R.C., Dickson, D.W., and Josephs, K.A.
- Abstract
Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.
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- 2010
- Full Text
- View/download PDF
29. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century(e–Pub ahead of print)(CME)
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Claassen, D.O., Josephs, K.A., Ahlskog, J.E., Silber, M.H., Tippmann-Peikert, M., and Boeve, B.F.
- Abstract
Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease PD, multiple system atrophy MSA, or dementia with Lewy bodies DLB).
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- 2010
- Full Text
- View/download PDF
30. Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia
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Whitwell, J.L., Avula, R., Senjem, M.L., Kantarci, K., Weigand, S.D., Samikoglu, A., Edmonson, H.A., Vemuri, P., Knopman, D.S., Boeve, B.F., Petersen, R.C., Josephs, K.A., and Jack, C.R.
- Abstract
To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA).
- Published
- 2010
- Full Text
- View/download PDF
31. Association of amyloid angiopathy with microbleeds in logopenic progressive aphasia: an imaging‐pathology study
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Caterina Giannini, Jeffrey L. Gunter, Mary M. Machulda, Anthony J. Spychalla, Keith A. Josephs, Aditya Raghunathan, Jennifer L. Whitwell, Marina Buciuc, Joseph R. Duffy, Dennis W. Dickson, Clifford R. Jack, Buciuc M., Duffy J.R., Machulda M.M., Spychalla A.J., Gunter J.L., Jack C.R., Giannini C., Raghunathan A., Dickson D.W., Josephs K.A., and Whitwell J.L.
- Subjects
Pathology ,medicine.medical_specialty ,positron emission tomography ,logopenic progressive aphasia ,Article ,microbleed ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,0302 clinical medicine ,Neuroimaging ,Aphasia ,medicine ,Humans ,magnetic resonance imaging ,030212 general & internal medicine ,Fisher's exact test ,Cerebral Hemorrhage ,medicine.diagnostic_test ,atypical Alzheimer’s disease ,business.industry ,Logopenic progressive aphasia ,Magnetic resonance imaging ,medicine.disease ,Superficial siderosis ,Cerebral Amyloid Angiopathy ,Neurology ,chemistry ,Frontal lobe ,Positron-Emission Tomography ,symbols ,Neurology (clinical) ,Cerebral amyloid angiopathy ,Pittsburgh compound B ,business ,030217 neurology & neurosurgery ,Human - Abstract
Background and purpose: Cerebral microbleeds (MB) and superficial siderosis (SS) are frequent neuroimaging findings in patients with logopenic progressive aphasia (LPA), often with frontal lobe predilection. Cerebral amyloid angiopathy (CAA) is hypothesized to be the major pathologic determinant of MB/SS in these patients; however, neuroimaging-pathologic data are limited. Methods: All patients who had been prospectively recruited by the Neurodegenerative Research Group at the Mayo Clinic (Rochester, MN) between 2010 and 2015 and met the following inclusion criteria were included: (i) received an antemortem LPA diagnosis, (ii) had a gradient-recalled echo T2*-weighted magnetic resonance imaging (MRI) performed, (iii) died and completed a brain autopsy. Demographic, genetic, neuroimaging, and clinical and pathologic characteristics were compared between patients with/without MB/SS. Two-tailed Fisher exact and Wilcoxon rank sum tests were used for comparison of categorical and continuous variables, respectively. Results: Thirteen patients met inclusion criteria, six (46%) had MB/SS on MRI. Moderate/severe CAA was associated with the presence of MB/SS (p=0.029). As expected, MB/SS most frequently involved the frontal lobes, followed by the parietal lobes. No clear associations were found between regional MB/SS distribution and regional distribution of CAA or hypometabolism on [18F]-fluorodeoxyglucose–positron emission tomography. There was some evidence for a regional association between MB/SS and uptake on Pittsburgh compound B, although not in all patients. No formal statistical analyses to assess topographic relationships were performed due to the small sample size. Conclusions: The presence of MB/SS is a strong indicator of underlying moderate/severe CAA in LPA, although the biological mechanisms underlying the topographic distribution of MB/SS remain unclear.
- Published
- 2020
32. Underlying pathology identified after 20 years of disease course in two cases of slowly progressive frontotemporal dementia syndromes
- Author
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Ryan J. Uitti, David T.W. Jones, Mary M. Machulda, Matt Baker, Keith A. Josephs, Nha Trang Thu Pham, Fatma Ozlem Hokelekli, Caterina Giannini, Val J. Lowe, Dennis W. Dickson, Jennifer L. Whitwell, Hokelekli F.O., Whitwell J.L., Machulda M.M., Jones D.T., Uitti R.J., Pham N.T.T., Giannini C., Baker M., Lowe V.J., Dickson D.W., and Josephs K.A.
- Subjects
Pathology ,medicine.medical_specialty ,slow progression ,phenocopy ,Autopsy ,tdp-43 ,050105 experimental psychology ,Article ,c9orf72 mutation ,Disease course ,03 medical and health sciences ,Personality changes ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Pick Disease of the Brain ,Slow progression ,argyrophilic grain disease ,mental disorders ,medicine ,Humans ,0501 psychology and cognitive sciences ,Phenocopy ,business.industry ,05 social sciences ,Brain ,Frontotemporal lobar degeneration ,Syndrome ,medicine.disease ,nervous system diseases ,Argyrophilic grain disease ,Frontotemporal Dementia ,Neurology (clinical) ,Frontotemporal Lobar Degeneration ,business ,030217 neurology & neurosurgery ,Human ,Frontotemporal dementia - Abstract
We report two cases from the frontotemporal lobar degeneration (FTLD) spectrum with a remarkably slow progression. The first case demonstrated insidious-onset behavioral symptoms and personality changes resembling behavioral variant of frontotemporal dementia, followed by a benign course of over 26 years, and his brain autopsy revealed the diffuse form of argyrophilic grain disease. The second case presented with slowly progressive cognitive and motor deficits, reminiscent of the corticobasal syndrome, deteriorated very slowly over 22 years and his brain autopsy revealed FTLD-TDP with C9ORF72 pathology. These two cases confirm the notion of slowly progressive frontotemporal lobar degeneration caused by an underlying FTLD pathology, rather than a phenocopy.
- Published
- 2021
33. Antemortem volume loss mirrors TDP-43 staging in older adults with non-frontotemporal lobar degeneration
- Author
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Joseph E. Parisi, Nirubol Tosakulwong, Hugo Botha, Keith A. Josephs, Christopher G. Schwarz, Gaël Chételat, Clifford R. Jack, Peter R. Martin, Melissa E. Murray, Alexandre Bejanin, Bradley F. Boeve, Matthew L. Senjem, Kejal Kantarci, Caterina Giannini, Dennis W. Dickson, Jennifer L. Whitwell, David S. Knopman, Ronald C. Petersen, Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bejanin A., Murray M.E., Martin P., Botha H., Tosakulwong N., Schwarz C.G., Senjem M.L., Chetelat G., Kantarci K., Jack C.R., Boeve B.F., Knopman D.S., Petersen R.C., Giannini C., Parisi J.E., Dickson D.W., Whitwell J.L., and Josephs K.A.
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,TDP-43 ,[SDV]Life Sciences [q-bio] ,Hippocampus ,tau Proteins ,Neuropathology ,Grey matter ,Temporal lobe ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,mental disorders ,medicine ,Humans ,Dementia ,tau ,Prospective Studies ,Gray Matter ,ComputingMilieux_MISCELLANEOUS ,Aged ,Aged, 80 and over ,neuropathology ,Amyloid beta-Peptides ,β-amyloid ,business.industry ,Brain ,nutritional and metabolic diseases ,Neurodegenerative Diseases ,radiological-pathological study ,Original Articles ,Frontotemporal lobar degeneration ,medicine.disease ,Entorhinal cortex ,Magnetic Resonance Imaging ,Temporal Lobe ,nervous system diseases ,DNA-Binding Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Frontotemporal Dementia ,Disease Progression ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Over the past decade, the transactive response DNA-binding protein of 43 kDa (TDP-43) has been recognized as a major protein in normal and pathological ageing, increasing the risk of cognitive impairment and dementia. In conditions distinct from the frontotemporal lobar degenerations, TDP-43 appears to progress in a stereotypical pattern. In the present study, we aimed at providing a better understanding of the effects of TDP-43 and other age-related neuropathologies on cross-sectional grey matter volume in a cohort of non-FTLD subjects. We included 407 individuals with an antemortem MRI and post-mortem brain tissue from the Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic Alzheimer's Disease Patient Registry, or the Mayo Clinic Study of Aging. All individuals were assigned pathological stages for TDP-43, tau, amyloid-β, Lewy bodies, argyrophilic grain disease and vascular pathologies. Robust regressions were performed in regions of interest and voxel-wise to explore the relationships between TDP-43 stages and grey matter volume while controlling for other pathologies. Grey matter volumes adjusted for pathological and demographic variables were also computed for each TDP-43-positive case to further characterize the sequential involvement of brain structures associated with TDP-43, irrespective of the TDP-43 staging scheme. Robust regressions showed that the extent of TDP-43 pathology was associated with the extent of grey matter atrophy. Specifically, we found that the volume in medial temporal regions (i.e. amygdala, entorhinal cortex, hippocampus) decreased progressively with advancing TDP-43 stages. Importantly, these effects were of similar magnitude to those related to tau stages. Additional analyses using adjusted grey matter volume demonstrated a sequential pattern of volume loss associated with TDP-43, starting within the medial temporal lobe, followed by early involvement of the temporal pole, and eventually encompassing additional temporal and frontal regions. Altogether, this study demonstrates the major and independent contribution of TDP-43 pathology on neurodegeneration and provides further insight into the regional distribution of TDP-43 in non-FTLD subjects. Along with previous studies, these findings emphasized the importance of targeting TDP-43 in future clinical trials to prevent its detrimental effect on grey matter volume and, eventually, cognition.
- Published
- 2019
34. Globular glial tauopathy presenting as semantic variant primary progressive aphasia
- Author
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Jonathan Graff-Radford, Caterina Giannini, Bradley F. Boeve, Keith A. Josephs, Dennis W. Dickson, Joseph E. Parisi, Graff-Radford J., Josephs K.A., Parisi J.E., Dickson D.W., Giannini C., and Boeve B.F.
- Subjects
0301 basic medicine ,Fatal outcome ,Semantic dementia ,Article ,Primary progressive aphasia ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Fatal Outcome ,Aphasia ,Humans ,Medicine ,Tauopathie ,Aged ,business.industry ,Extramural ,Frontotemporal lobar degeneration ,medicine.disease ,nervous system diseases ,Semantics ,030104 developmental biology ,Aphasia, Primary Progressive ,Tauopathies ,Female ,Neurology (clinical) ,Tauopathy ,medicine.symptom ,business ,Neuroscience ,Neuroglia ,030217 neurology & neurosurgery ,Frontotemporal dementia ,Human - Abstract
Semantic variant primary progressive aphasia (svPPA) most often is due to TAR DNA-binding protein 43 (TDP-43) pathology1. Herein, we report a novel case of svPPA due to a globular glial tauopathy.
- Published
- 2016
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