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Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia
Hu WT, McMillan C, Libon D, Leight S, Forman M, Lee VM, Trojanowski JQ, Grossman M.. Neurology, 2010-08-01
Topic: Amyloid, tau and blood-test diagnosis
Objective Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are hypothesized to cause clinically distinct forms of primary progressive aphasia (PPA) that predominantly affect expressive speech. AD is thought to cause logopenic progressive aphasia (LPA), and FTLD may cause progressive nonfluent aphasia (PNFA). We sought to determine the value of clinical characterization, neuropsychological analysis, and MRI atrophy in predicting pathology of LPA and PNFA. Methods Patients with LPA (n = 19) and patients with PNFA (n = 19) were evaluated with neuropsychological assessments, structural MRI, CSF analysis, and neuropathologic examination. Results Twelve of 19 patients with LPA (63%) and 6 of 19 patients with PNFA (32%) had neuropathologic findings or CSF biomarkers consistent with AD. Neuropsychological testing showed that naming was more impaired in patients with AD, and letter-guided fluency was more affected in patients with a non-AD disorder. Voxel-based morphometry analysis revealed that in patients with AD, patients with LPA and PNFA had significant posterior-superior temporal atrophy; in patients with non-AD, patients with LPA had peri-Sylvian atrophy and patients with PNFA had dorsolateral prefrontal and insular atrophy. Receiver operator characteristic curve analysis showed that combining neuropsychological testing with MRI atrophy pattern had 90% specificity for pathology or CSF biomarkers consistent with AD, and combining clinical features with neuropsychological analysis had 100% sensitivity for pathology or CSF biomarkers consistent with AD. Conclusions Neither PPA phenotyping nor imaging alone is a reliable predictor of pathology. Multimodal predictors, such as combining neuropsychological testing with MRI analysis, can improve noninvasive prediction of underlying pathology in nonfluent forms of PPA.
Key findings
- Results Twelve of 19 patients with LPA (63%) and 6 of 19 patients with PNFA (32%) had neuropathologic findings or CSF biomarkers consistent with AD.
- Neuropsychological testing showed that naming was more impaired in patients with AD, and letter-guided fluency was more affected in patients with a non-AD disorder.
- Voxel-based morphometry analysis revealed that in patients with AD, patients with LPA and PNFA had significant posterior-superior temporal atrophy; in patients with non-AD, patients with LPA had peri-Sylvian atrophy and patients with PNFA had dorsolateral prefrontal and insular atrophy.
- Receiver operator characteristic curve analysis showed that combining neuropsychological testing with MRI atrophy pattern had 90% specificity for pathology or CSF biomarkers consistent with AD, and combining clinical features with neuropsychological analysis had 100% sensitivity for pathology or CSF biomarkers consistent with AD.
Why it matters
Among patients with two forms of primary progressive aphasia, many had pathology or biomarkers consistent with Alzheimer's disease, and combining neuropsychological testing with MRI atrophy patterns improved identification. This is about predicting underlying pathology, not about treating or preventing Alzheimer's disease.
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Study details
- Participants19
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 19 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 102 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 9.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Owen A. Ross: h-index 95 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20713948) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Hu, W. T., McMillan, C., Libon, D., Leight, S., Forman, M., Lee, V. M., et al. (2010). Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia. Neurology. https://doi.org/10.1212/wnl.0b013e3181ed9c52
Vancouver
Hu WT, McMillan C, Libon D, Leight S, Forman M, Lee VM, et al. Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia. Neurology. 2010. doi:10.1212/wnl.0b013e3181ed9c52. PMID: 20713948.
BibTeX
@article{hu2010-20713948,
author = {Hu, W. T. and McMillan, C. and Libon, D. and Leight, S. and Forman, M. and Lee, V. M. and Trojanowski, J. Q. and Grossman, M.},
title = {{Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia}},
journal = {Neurology},
year = {2010},
doi = {10.1212/wnl.0b013e3181ed9c52},
pmid = {20713948},
url = {https://doi.org/10.1212/wnl.0b013e3181ed9c52}
}
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