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Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech
Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ et al.. Brain : a journal of neurology, 2006-04-13
Topic: Brain proteins, microglia and lab models
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 findings
- 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.
Why it matters
In 17 autopsy-examined people whose illness began with a degenerative speech or language disorder, all 11 who had apraxia of speech (a motor speech problem with slow, distorted speech) had tau-based pathology, while 5 of the 6 without it did not (P = 0.001); MRI linked apraxia of speech to the premotor and supplementary motor cortex and non-fluent aphasia to the anterior peri-sylvian region. None of the cases had Alzheimer's disease: the diagnoses were progressive supranuclear palsy, corticobasal degeneration, FTLD with ubiquitin-only changes and Pick's disease. This small case series helps separate apraxia of speech from aphasia and link it to underlying pathology, but it tests no treatment and the authors say the classifications still need refining.
Study details
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2006 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 1 / 2 | Blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 693 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.5 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 4 / 6 | Cited 18.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 43 other studies in this library |
| Still being cited | 3 / 4 | Cited 65 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Keith A. Josephs: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16613895) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Josephs, K. A., Duffy, JR., Strand, E. A., Whitwell, J. L., Layton, K. F., Parisi, J. E., et al. (2006). Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain : a journal of neurology. https://doi.org/10.1093/brain/awl078
Vancouver
Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain : a journal of neurology. 2006. doi:10.1093/brain/awl078. PMID: 16613895.
BibTeX
@article{josephs2006-16613895,
author = {Josephs, K. A. and Duffy, JR. and Strand, E. A. and Whitwell, J. L. and Layton, K. F. and Parisi, J. E. and Hauser, M. F. and Witte, R. J. and others},
title = {{Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech}},
journal = {Brain : a journal of neurology},
year = {2006},
doi = {10.1093/brain/awl078},
pmid = {16613895},
url = {https://doi.org/10.1093/brain/awl078}
}
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