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Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula
Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR.. Brain : a journal of neurology, 2003-08-05
Topic: Brain proteins, microglia and lab models
Progressive non-fluent aphasia (PNFA) is a syndrome in which patients lose the ability to communicate fluently in the context of relative preservation of single word comprehension and non-linguistic cognitive abilities. Neuroimaging in case studies with PNFA has failed to identify a consistent neural substrate for the language disorder. In this study of a group of patients (n=10) whose presenting complaint was progressive dysfluency, resting cerebral metabolism was measured using [18F]fluorodeoxyglucose-PET and analysed with the technique of statistical parametric mapping (SPM). Regional atrophy was assessed with voxel-based morphometry (VBM). Seven patients had a 'pure' PNFA syndrome, while the remaining three had additional features of a more pervasive dementia. Compared with controls, the patients showed hypometabolism in several regions that, most notably, included the left anterior insula/frontal opercular region. The VBM analysis revealed only one small area of atrophy in the left peri-Sylvian region. Analysis of the pure PNFA cases (n=7) relative to controls yielded qualitatively similar results to those of the whole group, suggesting that these cases were also at risk of a more generalized dementia, a finding borne out in subsequent follow-up of two cases to date. The PNFA group was then compared with a group with Alzheimer's disease (n=10) whose clinical profile did not include non-fluent aphasic features. In this analysis, the only persisting hypometabolic region was that centred over the left anterior insula. VBM did not identify any regional differences in atrophy between PNFA and Alzheimer's disease. In the light of current theories of fluent language production, the findings offer anatomical evidence that the breakdown in fluency is due to a motor articulatory planning deficit (speech apraxia) combined with a variable degree of agrammatism.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nestor, P. J., Graham, N. L., Fryer, T. D., Williams, G. B., Patterson, K., & Hodges, JR. (2003). Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain : a journal of neurology. https://doi.org/10.1093/brain/awg240
Vancouver
Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR. Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain : a journal of neurology. 2003. doi:10.1093/brain/awg240. PMID: 12902311.
BibTeX
@article{nestor2003-12902311,
author = {Nestor, P. J. and Graham, N. L. and Fryer, T. D. and Williams, G. B. and Patterson, K. and Hodges, JR.},
title = {{Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula}},
journal = {Brain : a journal of neurology},
year = {2003},
doi = {10.1093/brain/awg240},
pmid = {12902311},
url = {https://doi.org/10.1093/brain/awg240}
}
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Key findings
- Compared with controls, the patients showed hypometabolism in several regions that, most notably, included the left anterior insula/frontal opercular region.
- The VBM analysis revealed only one small area of atrophy in the left peri-Sylvian region.
- Analysis of the pure PNFA cases (n=7) relative to controls yielded qualitatively similar results to those of the whole group, suggesting that these cases were also at risk of a more generalized dementia, a finding borne out in subsequent follow-up of two cases to date.
- The PNFA group was then compared with a group with Alzheimer's disease (n=10) whose clinical profile did not include non-fluent aphasic features.
Why it matters
In this study of 10 patients with progressive non-fluent aphasia, PET showed hypometabolism including the left anterior insula/frontal opercular region, while voxel-based morphometry revealed only one small area of atrophy. It describes brain changes in this language condition and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded 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 | 2003 — 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 | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 326 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.0 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 3 / 6 | Cited 6.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Peter J. Nestor: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12902311) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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