{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:15:53Z","timestamp":1790097353979,"version":"4.0.1"},"reference-count":132,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Communication Disorders","doi-asserted-by":"crossref","award":["R01NS075075"],"award-info":[{"award-number":["R01NS075075"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Communication Disorders","doi-asserted-by":"crossref","award":["R01NS085770"],"award-info":[{"award-number":["R01NS085770"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute on Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01AG056258"],"award-info":[{"award-number":["R01AG056258"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute on Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01AG62566"],"award-info":[{"award-number":["R01AG62566"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute on Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K08AG065463"],"award-info":[{"award-number":["K08AG065463"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute on Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["P30AG013854"],"award-info":[{"award-number":["P30AG013854"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Davee Foundation and the Jeanine Jones Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer\u2019s disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick\u2019s disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.2\u2009\u00b1\u20092.6\u2009years) and shortest in TDP(A) (7.1\u2009\u00b1\u20092.4\u2009years). A subset of 68 right-handed participants entered longitudinal investigations. They were classified as logopenic, agrammatic\/non-fluent or semantic by quantitative algorithms. Each variant had a preferred but not invariant neuropathological correlate.<\/jats:p>\n                  <jats:p>Seventy-seven per cent of logopenics had ADNC, 56% of agrammatics had corticobasal degeneration\/progressive supranuclear palsy or Pick\u2019s disease and 89% of semantics had TDP(C). Word comprehension impairments had strong predictive power for determining underlying neuropathology positively for TDP(C) and negatively for ADNC. Cortical atrophy was smallest in corticobasal degeneration\/progressive supranuclear palsy and largest in TDP(A). Atrophy encompassed posterior frontal but not temporoparietal cortex in corticobasal degeneration\/progressive supranuclear palsy, anterior temporal but not frontoparietal cortex in TDP(C), temporofrontal but not parietal cortex in Pick\u2019s disease and all three lobes with ADNC or TDP(A).<\/jats:p>\n                  <jats:p>There were individual deviations from these group patterns, accounting for less frequent clinicopathologic associations. The one common denominator was progressive asymmetric atrophy overwhelmingly favouring the left hemisphere language network. Comparisons of ADNC in typical amnestic versus atypical aphasic dementia and of TDP in type A versus type C revealed fundamental biological and clinical differences, suggesting that members of each pair may constitute distinct clinicopathologic entities despite identical downstream proteinopathies. Individual TDP(C) participants with unilateral left temporal atrophy displayed word comprehension impairments without additional object recognition deficits, helping to dissociate semantic primary progressive aphasia from semantic dementia. When common and uncommon associations were considered in the set of 68 participants, one neuropathology was found to cause multiple clinical subtypes, and one subtype of primary progressive aphasia to be caused by multiple neuropathologies, but with different probabilities. Occasionally, expected clinical manifestations of atrophy sites were absent, probably reflecting individual peculiarities of language organization.<\/jats:p>\n                  <jats:p>The hemispheric asymmetry of neurodegeneration and resultant language impairment in primary progressive aphasia reflect complex interactions among the cellular affinities of the degenerative disease, the constitutive biology of language cortex, familial or developmental vulnerabilities of this network and potential idiosyncrasies of functional anatomy in the affected individual.<\/jats:p>","DOI":"10.1093\/brain\/awab410","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T08:21:00Z","timestamp":1636100460000},"page":"2133-2148","source":"Crossref","is-referenced-by-count":59,"title":["Neuropathological fingerprints of survival, atrophy and language in primary progressive aphasia"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5731-851X","authenticated-orcid":false,"given":"M Marsel","family":"Mesulam","sequence":"first","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Davee Department of Neurology, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-1998","authenticated-orcid":false,"given":"Christina A","family":"Coventry","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen H","family":"Bigio","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Pathology, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaiashre","family":"Sridhar","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Gill","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Preventive Medicine, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela J","family":"Fought","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Preventive Medicine, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia K","family":"Thompson","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"School of Communication, Northwestern University , Evanston, IL 60208 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changiz","family":"Geula","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gefen","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Pathology, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-5205","authenticated-orcid":false,"given":"Sandra","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J","family":"Rogalski","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine , Chicago, IL 60611 , USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine , Chicago, IL 60611 , 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