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Title: Quantitative classification of primary progressive aphasia at early and mild impairment stages. Author: Mesulam MM, Wieneke C, Thompson C, Rogalski E, Weintraub S. Journal: Brain; 2012 May; 135(Pt 5):1537-53. PubMed ID: 22525158. Abstract: The characteristics of early and mild disease in primary progressive aphasia are poorly understood. This report is based on 25 patients with aphasia quotients >85%, 13 of whom were within 2 years of symptom onset. Word-finding and spelling deficits were the most frequent initial signs. Diagnostic imaging was frequently negative and initial consultations seldom reached a correct diagnosis. Functionality was preserved, so that the patients fit current criteria for single-domain mild cognitive impairment. One goal was to determine whether recently published classification guidelines could be implemented at these early and mild disease stages. The quantitative testing of the recommended core and ancillary criteria led to the classification of ∼80% of the sample into agrammatic, logopenic and semantic variants. Biological validity of the resultant classification at these mild impairment stages was demonstrated by clinically concordant cortical atrophy patterns. A two-dimensional template based on orthogonal mapping of word comprehension and grammaticality provided comparable accuracy and led to a flexible road map that can guide the classification process quantitatively or qualitatively. Longitudinal evaluations of initially unclassifiable patients showed that the semantic variant can be preceded by a prodromal stage of focal left anterior temporal atrophy during which prominent anomia exists without word comprehension or object recognition impairments. Patterns of quantitative tests justified the distinction of grammar from speech abnormalities and the desirability of using the 'agrammatic' designation exclusively for loss of grammaticality, regardless of fluency or speech status. Two patients with simultaneous impairments of grammatical sentence production and word comprehension displayed focal atrophy of the inferior frontal gyrus and the anterior temporal lobe. These patients represent a fourth variant of 'mixed' primary progressive aphasia. Quantitative criteria were least effective in the distinction of the agrammatic from the logopenic variant and left considerable latitude to clinical judgement. The widely followed recommendation to wait for 2 years of relatively isolated and progressive language impairment before making a definitive diagnosis of primary progressive aphasia has promoted diagnostic specificity, but has also diverted attention away from early and mild disease. This study shows that this recommendation is unnecessarily restrictive and that quantitative guidelines can be implemented for the valid root diagnosis and subtyping of mildly impaired patients within 2 years of symptom onset. An emphasis on early diagnosis will promote a better characterization of the disease stages where therapeutic interventions are the most likely to succeed.[Abstract] [Full Text] [Related] [New Search]