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Ann Neurol. 2006 Jan;59(1):156-65.

Clinical and pathological characterization of progressive aphasia.

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University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.



The clinical and neuropathological categorization of patients presenting with progressive aphasia is an area of controversy. This study aimed to characterize a large group of progressive aphasic patients from a single center (n = 38), first clinically by case note review, and then pathologically.


Hierarchical cluster analysis of the cases according to their clinical language deficits was used to establish an unbiased, data-driven classification.


This analysis revealed two groups of cases corresponding to the syndromes of progressive nonfluent aphasia (n = 23) and semantic dementia (n = 15). Postmortem analysis showed a majority in both groups of pathologies from the spectrum of frontotemporal lobar degeneration: the most frequent were non-Alzheimer's disease (AD) tauopathy in the nonfluent cases (10 of 23) and frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions in the fluent cases (8 of 15). Despite rigorous exclusion of cases with clinically significant memory deficits or other cognitive impairments, the pathology of AD was present in approximately one third of each group (overall 12 of 38), although often with an atypical neuroanatomical distribution.


Progressive aphasia is best seen as a composite of two conditions, on both clinical and pathological levels: progressive nonfluent aphasia and semantic dementia.

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