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Brain Advance Access originally published online on April 13, 2006
Brain 2006 129(6):1385-1398; doi:10.1093/brain/awl078
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech

Keith A. Josephs1,2, Joseph R. Duffy3, Edyth A. Strand3, Jennifer L. Whitwell4, Kenneth F. Layton7, Joseph E. Parisi5, Mary F. Hauser6,8, Robert J. Witte7, Bradley F. Boeve1,2, David S. Knopman1, Dennis W. Dickson6,8, Clifford R. Jack, Jr4 and Ronald C. Petersen1

1 Departments of Neurology, Divisions of Behavioral Neurology Mayo Clinic, Rochester, MN, USA 2 Departments of Neurology, Divisions of Movement Disorders Mayo Clinic, Rochester, MN, USA 3 Departments of Neurology, Divisions of Speech Pathology Mayo Clinic, Rochester, MN, USA 4 Departments of Neurology, Radiology Research Mayo Clinic, Rochester, MN, USA 5 Departments of Neurology, Laboratory Medicine and Pathology Mayo Clinic, Rochester, MN, USA 6 Departments of Neurology, Nuclear Medicine Mayo Clinic, Rochester, MN, USA 7 Departments of Neurology, Diagnostic Radiology Mayo Clinic, Rochester, MN, USA 8 Division of Neuroscience (Neuropathology) Mayo Clinic, Jacksonville, FL, USA

Correspondence to: Keith A. Josephs, MST, MD, Department of Neurology, Divisions of Movement Disorders and Behavioral Neurology, Mayo Clinic, Rochester, MN 55905, USA E-mail: josephs.keith{at}mayo.edu

Apraxia of speech (AOS) is a motor speech disorder characterized by slow speaking rate, abnormal prosody and distorted sound substitutions, additions, repetitions and prolongations, sometimes accompanied by groping, and trial and error articulatory movements. Although AOS is frequently subsumed under the heading of aphasia, and indeed most often co-occurs with aphasia, it can be the predominant or even the sole manifestation of a degenerative neurological disease. In this study we determine whether the clinical classifications of aphasia and AOS correlated with pathological diagnoses and specific biochemical and anatomical structural abnormalities. Seventeen cases with initial diagnoses of a degenerative aphasia or AOS were re-classified independently by two speech-language pathologists—blinded to pathological and biochemical findings—into one of five operationally defined categories of aphasia and AOS. Pathological diagnoses in the 17 cases were progressive supranuclear palsy in 6, corticobasal degeneration in 5, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes in 5 and Pick's disease in 1. Magnetic resonance imaging analysis using voxel-based morphometry (VBM), and single photon emission tomography were completed, blinded to the clinical diagnoses, and clinicoimaging and clinicopathological associations were then sought. Interjudge clinical classification reliability was 87% ({kappa} = 0.8) for all evaluations. Eleven cases had evidence of AOS, of which all (100%) had a pathological diagnosis characterized by underlying tau biochemistry, while five of the other six cases without AOS did not have tau biochemistry (P = 0.001). A majority of the 17 cases had more than one yearly evaluation, demonstrating the evolution of the speech and language syndromes, as well as motor signs. VBM revealed the premotor and supplemental motor cortices to be the main cortical regions associated with AOS, while the anterior peri-sylvian region was associated with non-fluent aphasia. Refining the classification of the degenerative aphasias and AOS may be necessary to improve our understanding of the relationships among behavioural, pathological and imaging correlations.

Key Words: premotor cortex; supplementary motor cortex; progressive supranuclear palsy; apraxia of speech; aphasia

Abbreviations: AOS, apraxia of speech; CBD, corticobasal degeneration; FTLD, frontotemporal lobar degeneration; GM, grey matter; NVOA, non-verbal oral apraxia; PiD, Pick's disease; PNFA, progressive non-fluent aphasia; PPA, primary progressive aphasia; PSP, progressive supranuclear palsy; SD, semantic dementia; SPECT, single photon emission computer tomography; VBM, voxel-based morphometry

Received September 21, 2005. Revised March 3, 2006. Accepted March 8, 2006.


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