Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia

Santos-Santos, Miguel Ángel; Rabinovici, Gil D.; Laccarino, Leonardo; Ayakta, Nagehan; Tammewar, Gautam; Lobach, Iryna; Henry, Maya L.; Hubbard, H. Isabel; Mandelli, Maria Luisa; Spinelli, Edoardo; Miller, Zachary A.; Pressman, Peter S.; O'Neil, James P.; Ghosh, Pla; Lazaris, Andreas; Meyer, Marita; Watson, Christa L.; Yoon, Soo Jin; Rosen, Howard J.; Grinberg, Lea T.; Seeley, William W.; Miller, Bruce L.; Jagust, William J.; Gorno Tempini, Maria Luisa

Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia

IMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of pr...

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Authors:	Santos-Santos, Miguel Ángel, Rabinovici, Gil D., Laccarino, Leonardo, Ayakta, Nagehan, Tammewar, Gautam, Lobach, Iryna, Henry, Maya L., Hubbard, H. Isabel, Mandelli, Maria Luisa, Spinelli, Edoardo, Miller, Zachary A., Pressman, Peter S., O'Neil, James P., Ghosh, Pla, Lazaris, Andreas, Meyer, Marita, Watson, Christa L., Yoon, Soo Jin, Rosen, Howard J., Grinberg, Lea T., Seeley, William W., Miller, Bruce L., Jagust, William J., Gorno Tempini, Maria Luisa
Format:	article
Status:	Versión aceptada para publicación
Publication Date:	2018
Country:	España
Institution:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/123993
Online Access:	https://hdl.handle.net/2445/123993
Access Level:	Open access
Keyword:	Malaltia d'Alzheimer Marcadors bioquímics Alzheimer's disease Biochemical markers

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network_acronym_str	ES
network_name_str	España
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dc.title.none.fl_str_mv	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
title	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
spellingShingle	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia Santos-Santos, Miguel Ángel Malaltia d'Alzheimer Marcadors bioquímics Alzheimer's disease Biochemical markers
title_short	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
title_full	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
title_fullStr	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
title_full_unstemmed	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
title_sort	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia
dc.creator.none.fl_str_mv	Santos-Santos, Miguel Ángel Rabinovici, Gil D. Laccarino, Leonardo Ayakta, Nagehan Tammewar, Gautam Lobach, Iryna Henry, Maya L. Hubbard, H. Isabel Mandelli, Maria Luisa Spinelli, Edoardo Miller, Zachary A. Pressman, Peter S. O'Neil, James P. Ghosh, Pla Lazaris, Andreas Meyer, Marita Watson, Christa L. Yoon, Soo Jin Rosen, Howard J. Grinberg, Lea T. Seeley, William W. Miller, Bruce L. Jagust, William J. Gorno Tempini, Maria Luisa
author	Santos-Santos, Miguel Ángel
author_facet	Santos-Santos, Miguel Ángel Rabinovici, Gil D. Laccarino, Leonardo Ayakta, Nagehan Tammewar, Gautam Lobach, Iryna Henry, Maya L. Hubbard, H. Isabel Mandelli, Maria Luisa Spinelli, Edoardo Miller, Zachary A. Pressman, Peter S. O'Neil, James P. Ghosh, Pla Lazaris, Andreas Meyer, Marita Watson, Christa L. Yoon, Soo Jin Rosen, Howard J. Grinberg, Lea T. Seeley, William W. Miller, Bruce L. Jagust, William J. Gorno Tempini, Maria Luisa
author_role	author
author2	Rabinovici, Gil D. Laccarino, Leonardo Ayakta, Nagehan Tammewar, Gautam Lobach, Iryna Henry, Maya L. Hubbard, H. Isabel Mandelli, Maria Luisa Spinelli, Edoardo Miller, Zachary A. Pressman, Peter S. O'Neil, James P. Ghosh, Pla Lazaris, Andreas Meyer, Marita Watson, Christa L. Yoon, Soo Jin Rosen, Howard J. Grinberg, Lea T. Seeley, William W. Miller, Bruce L. Jagust, William J. Gorno Tempini, Maria Luisa
author2_role	author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Malaltia d'Alzheimer Marcadors bioquímics Alzheimer's disease Biochemical markers
topic	Malaltia d'Alzheimer Marcadors bioquímics Alzheimer's disease Biochemical markers
description	IMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTS This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURES Clinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.
publishDate	2018
dc.date.none.fl_str_mv	2018 2018 2018 2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/123993
url	https://hdl.handle.net/2445/123993
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Versió postprint del document publicat a: https://doi.org/10.1001/jamaneurol.2017.4309 Jama Neurology, 2018, Vol. 75, Issue 3, P. 342-352 https://doi.org/10.1001/jamaneurol.2017.4309
dc.rights.none.fl_str_mv	(c) American Medical Association, 2018 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) American Medical Association, 2018
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Amer Medical Assoc
publisher.none.fl_str_mv	Amer Medical Assoc
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling	Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive AphasiaSantos-Santos, Miguel ÁngelRabinovici, Gil D.Laccarino, LeonardoAyakta, NagehanTammewar, GautamLobach, IrynaHenry, Maya L.Hubbard, H. IsabelMandelli, Maria LuisaSpinelli, EdoardoMiller, Zachary A.Pressman, Peter S.O'Neil, James P.Ghosh, PlaLazaris, AndreasMeyer, MaritaWatson, Christa L.Yoon, Soo JinRosen, Howard J.Grinberg, Lea T.Seeley, William W.Miller, Bruce L.Jagust, William J.Gorno Tempini, Maria LuisaMalaltia d'AlzheimerMarcadors bioquímicsAlzheimer's diseaseBiochemical markersIMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTS This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURES Clinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.Amer Medical Assoc2018201820182018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/123993Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1001/jamaneurol.2017.4309Jama Neurology, 2018, Vol. 75, Issue 3, P. 342-352https://doi.org/10.1001/jamaneurol.2017.4309(c) American Medical Association, 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1239932026-05-29T05:05:01Z
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Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia

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