This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA-nonfluent/agrammatic, semantic, and logopenic-were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations. Neurology

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E ε4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.Isolated speech and language difficulties are often the first symptoms of focal forms of neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). 1,2 Alzheimer's disease (AD) patients also have been shown to present with atypical focal cognitive manifestations, including fluent and nonfluent progressive aphasia. 3-7 When speech and language deficits remain the only complaint for at least 2 years, the term primary progressive aphasia (PPA) has been applied. 8Pathologically, the most frequent finding in PPA is an FTLD-type of damage such as dementia lacking distinctive pathology (DLDH) 9-11 or Pick's disease. 12,13 Cases with AD, 3 Creutzfeldt-Jakob disease, 1,4 and FTLD with motor neuron disease (FTLD-MND) pathology also have been reported 15 (for review, see Mesulam, 16 Grossman, 17 and Black 18 ). Kertesz first included CBD in the FTLD/Pick's spectrum of diseases and recently reported four PPA cases with pathologically proven CBD. 12,19 Address correspondence to Dr Gorno-Tempini, UCSF Memory and Aging Center, 350 Parnassus Avenue, Suite 706, Box 1207. San Francisco, CA 94143. E-mail: marilu@itsa.ucsf.edu. NIH Public Access Author ManuscriptAnn Neurol. Author manuscript; available in PMC 2008 May 1. Published in final edited form as:Ann Neurol. 2004 March ; 55(3): 335-346. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDifferent clinical presentations of PPA have been reported, but large studies that investigate both cognitive and neuroimaging findings in the same group of patients are still lacking. Here, we consider the clinical variants that have be...

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The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which lesioned brain areas might affect language comprehension. Sixty-four chronic left hemisphere stroke patients were evaluated on 11 subtests of the Curtiss-Yamada Comprehensive Language Evaluation - Receptive (CYCLE-R; Curtiss, S., & Yamada, J. (1988). Curtiss-Yamada Comprehensive Language Evaluation. Unpublished test, UCLA). Eight right hemisphere stroke patients and 15 neurologically normal older controls also participated. Patients were required to select a single line drawing from an array of three or four choices that best depicted the content of an auditorily-presented sentence. Patients' lesions obtained from structural neuroimaging were reconstructed onto templates and entered into a voxel-based lesion-symptom mapping (VLSM; Bates, E., Wilson, S., Saygin, A. P., Dick, F., Sereno, M., Knight, R. T., & Dronkers, N. F. (2003). Voxel-based lesion-symptom mapping. Nature Neuroscience, 6(5), 448-450.) analysis along with the behavioral data. VLSM is a brain-behavior mapping technique that evaluates the relationships between areas of injury and behavioral performance in all patients on a voxel-by-voxel basis, similar to the analysis of functional neuroimaging data. Results indicated that lesions to five left hemisphere brain regions affected performance on the CYCLE-R, including the posterior middle temporal gyrus and underlying white matter, the anterior superior temporal gyrus, the superior temporal sulcus and angular gyrus, mid-frontal cortex in Brodmann's area 46, and Brodmann's area 47 of the inferior frontal gyrus. Lesions to Broca's and Wernicke's areas were not found to significantly alter language comprehension on this particular measure. Further analysis suggested that the middle temporal gyrus may be more important for comprehension at the word level, while the other regions may play a greater role at the level of the sentence. These results are consistent with those seen in recent functional neuroimaging studies and offer complementary data in the effort to understand the brain areas underlying language comprehension.