title: Primary progressive aphasia and the evolving neurology of the language network.
abstract: Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: M-Marsel
authors.initials: MM
authors.lastname: Mesulam
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Rogalski
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Wieneke
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hurley
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Changiz
authors.initials: C
authors.lastname: Geula
authors.affiliation: Department of Neuropathology, Northwestern University Feinberg School of Medicine, 710 North Fairbanks Court, Chicago, IL 60611, USA.
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.affiliation: Department of Communication Sciences and Disorders, Northwestern University, 633 Clark Street, Evanston, IL 60208, USA.
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Thompson
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Centre, 320 East Superior Street, Searle Building, 11-450, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Weintraub
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D018888:Aphasia, Primary Progressive / Q000145:classification / Q000473:pathology / Q000503:physiopathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D065711:Broca Area / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D057174:Frontotemporal Lobar Degeneration / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D065813:Wernicke Area / Q000473:pathology / Q000503:physiopathology