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Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia
Mesulam M, Wicklund A, Johnson N, Rogalski E, Léger GC, Rademaker A, Weintraub S, Bigio EH.. Annals of neurology, 2008-06-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype. Methods Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type. Results The sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA. Interpretation Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process.
Key findings
- Objective To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype.
- Results The sample contained mostly logopenic, agrammatic, and mixed forms of PPA.
- Interpretation Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level.
- However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients.
Why it matters
In 23 consecutive autopsies of people with primary progressive aphasia, a dementia that starts with language problems, all six with the agrammatic form had frontotemporal lobar degeneration, and seven of the eleven with the logopenic form had Alzheimer's disease. The authors conclude that subtyping "helps to predict" the underlying disease "at the group level", but that "no clinical predictor is completely reliable in individual patients"; APOE4 did not predict Alzheimer's pathology in this group. It is a small diagnosis-and-pathology study, not about treating or preventing Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 52/100
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 (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 2008 — within 20 year(s) of the newest study here |
| 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 521 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.1 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 5 / 6 | Cited 23.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 42 other studies in this library |
| Still being cited | 2 / 4 | Cited 48 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Eileen H. Bigio: h-index 89 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Northwestern University: institution h-index 1,592 (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 18412267) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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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
Mesulam, M., Wicklund, A., Johnson, N., Rogalski, E., Léger, G. C., Rademaker, A., et al. (2008). Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Annals of neurology. https://doi.org/10.1002/ana.21388
Vancouver
Mesulam M, Wicklund A, Johnson N, Rogalski E, Léger GC, Rademaker A, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Annals of neurology. 2008. doi:10.1002/ana.21388. PMID: 18412267.
BibTeX
@article{mesulam2008-18412267,
author = {Mesulam, M. and Wicklund, A. and Johnson, N. and Rogalski, E. and Léger, G. C. and Rademaker, A. and Weintraub, S. and Bigio, E. H.},
title = {{Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia}},
journal = {Annals of neurology},
year = {2008},
doi = {10.1002/ana.21388},
pmid = {18412267},
url = {https://doi.org/10.1002/ana.21388}
}
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