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Neurology. 2010 Jul 27;75(4):358-66. doi: 10.1212/WNL.0b013e3181ea15e8.

Cortical neuroanatomic correlates of symptom severity in primary progressive aphasia.

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MGH Frontotemporal Dementia Unit, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.



To test the validity and reliability of a new measure of clinical impairment in primary progressive aphasia (PPA), the Progressive Aphasia Severity Scale (PASS), and to investigate relationships with MRI-based cortical thickness biomarkers for localizing and quantifying the severity of anatomic abnormalities.


Patients with PPA were rated using the PASS and underwent performance-based language testing and MRI scans that were processed for cortical thickness measures.


The level of impairment in PASS fluency, syntax/grammar, and word comprehension showed strong specific correlations with performance-based measures of these domains of language, and demonstrated high interrater reliability. Left inferior frontal thinning correlated with impairment in fluency and grammar/syntax, while left temporopolar thinning correlated with impairment in word comprehension. Discriminant function analysis demonstrated that a combination of left inferior frontal, left temporopolar, and left superior temporal sulcal thickness separated the 3 PPA subtypes from each other with 100% accuracy (87% accuracy in a leave-one-out analysis).


The PASS, a novel measure of the severity of clinical impairment within domains of language typically affected in PPA, demonstrates reliable and valid clinical-behavioral properties. Furthermore, the presence of impairment in individual PASS domains demonstrates specific relationships with focal abnormalities in particular brain regions and the severity of impairment is strongly related to the severity of anatomic abnormality within the relevant brain region. These anatomic imaging biomarkers perform well in classifying PPA subtypes. These data provide robust support for the value of this novel clinical measure and the new imaging measure as markers for potential use in clinical research and trials in PPA.

[Indexed for MEDLINE]
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