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Oxford University Press, Brain, 10(134), p. 3030-3043, 2011

DOI: 10.1093/brain/awr216

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Subtypes of progressive aphasia: application of the international consensus criteria and validation using β-amyloid imaging

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This paper is available in a repository.

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Abstract

Primary progressive aphasia comprises a heterogeneous group of neurodegenerative conditions with diverse clinical profiles and underlying pathological substrates. A major development has been the publication of the recent International Consensus Criteria for the three major variants namely: semantic, non-fluent/agrammatic and logopenic. The logopenic variant is assumed to represent an atypical presentation of Alzheimer pathology although evidence for this is, at present, limited. The semantic and non-fluent/agrammatic variants are largely associated with frontotemporal lobar degeneration with TDP-43 and tau pathology, respectively. The applicability of the International Consensus Criteria to an unselected clinical sample is unknown and no agreed clinical evaluation scale on which to derive the diagnosis exists. We assessed 47 consecutive cases of primary progressive aphasic seen over a 3-year period in a specialist centre, using a newly developed progressive aphasia language scale. A subgroup of 30 cases underwent (11)C-labelled Pittsburgh Compound B positron emission tomography imaging, a putative biomarker of Alzheimer's disease that detects β-amyloid accumulation, and they were compared with an age-matched group (n = 10) with typical, predominately amnestic Alzheimer's disease. The application of an algorithm based on four key speech and language variables (motor speech disorders, agrammatism, single-word comprehension and sentence repetition) classified 45 of 47 (96%) of patients and showed high concordance with the gold standard expert clinical diagnosis based on the International Consensus Criteria. The level of neocortical β-amyloid burden varied considerably across aphasic variants. Of 13 logopenic patients, 12 (92%) had positive β-amyloid uptake. In contrast, one of nine (11%) semantic variant and two of eight (25%) non-fluent/agrammatic cases were positive. The distribution of β-amyloid across cortical regions of interest was identical in cases with the logopenic variant to that of patients with typical Alzheimer's disease although the total load was lower in the aphasic cases. Impairments of sentence repetition and sentence comprehension were positively correlated with neocortical burden of β-amyloid, whereas impaired single-word comprehension showed a negative correlation. The International Consensus Criteria can be applied to the majority of cases with primary progressive aphasic using a simple speech and language assessment scale based upon four key variables. β-amyloid imaging confirms the higher rate of Alzheimer pathology in the logopenic variant and, in turn, the low rates in the other two variants. The study offers insight into the biological basis of clinical manifestations of Alzheimer's disease, which appear topographically independent of β-amyloid load.