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Atypical Alzheimer's disease phenotypes with normal or borderline PET biomarker profiles
Neha Atulkumar Singh, Jonathan Graff-Radford, Mary M Machulda, Christopher G Schwarz, Matthew C Baker, Rosa Rademakers, Nilufer Ertekin-Taner, Val J Lowe et al.. Journal of neurology, 2022-08-24
Topic: Plasma and spinal-fluid biomarkers
Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are clinical syndromes that commonly have underlying Alzheimer's disease (AD), although non-AD pathologies have also been reported. PET imaging allows for identification of beta-amyloid (Aβ) and tau in AD, so we aimed to assess these in a large cohort to identify patients that do not have evidence for biomarker-defined AD. Eight-one patients, 47 PCA and 34 LPA, underwent extensive neurological and neuropsychological testing, [11C] Pittsburgh compound B, [18F] flortaucipir and [18F] fluorodeoxyglucose PETs. Global Aβ and tau-PET standardized uptake value ratios (SUVRs) were plotted for all patients and outliers, and patients with abnormally low SUVRs compared to the biomarker-classic cohort were identified. Six (7.4%) biomarker-outlier cases were identified, and three patterns were observed: (i) negative/borderline Aβ-PET and striking widespread tau-PET uptake (two LPA); (ii) negative/borderline Aβ-PET and low tau-PET uptake (three PCA) and (iii) elevated Aβ-PET uptake but mild focal tau-PET uptake (one LPA). Among the unusual patients in group ii, two patients showed no abnormal tau uptake suggesting non-AD pathology, with one developing features of cortico-basal syndrome and the other dementia with Lewy bodies. The remaining patient showed very mild focal tau uptake. This study demonstrates that a small minority (~ 8%) of PCA and LPA patients do not show the typical striking patterns of Aβ and tau PET uptake, with only 2% showing absence of both proteins. These findings will help inform the use of molecular PET in clinical treatment trials that include patients with atypical phenotypes of AD.
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APA 7th
Singh, N. A., Graff-Radford, J., Machulda, M. M., Schwarz, C. G., Baker, M. C., Rademakers, R., et al. (2022). Atypical Alzheimer's disease phenotypes with normal or borderline PET biomarker profiles. Journal of neurology. https://doi.org/10.1007/s00415-022-11330-5
Vancouver
Singh NA, Graff-Radford J, Machulda MM, Schwarz CG, Baker MC, Rademakers R, et al. Atypical Alzheimer's disease phenotypes with normal or borderline PET biomarker profiles. Journal of neurology. 2022. doi:10.1007/s00415-022-11330-5. PMID: 36001141.
BibTeX
@article{singh2022-36001141,
author = {Singh, Neha Atulkumar and Graff-Radford, Jonathan and Machulda, Mary M and Schwarz, Christopher G and Baker, Matthew C and Rademakers, Rosa and Ertekin-Taner, Nilufer and Lowe, Val J and others},
title = {{Atypical Alzheimer's disease phenotypes with normal or borderline PET biomarker profiles}},
journal = {Journal of neurology},
year = {2022},
doi = {10.1007/s00415-022-11330-5},
pmid = {36001141},
url = {https://doi.org/10.1007/s00415-022-11330-5}
}
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Key findings
- Global Aβ and tau-PET standardized uptake value ratios (SUVRs) were plotted for all patients and outliers, and patients with abnormally low SUVRs compared to the biomarker-classic cohort were identified.
- These findings will help inform the use of molecular PET in clinical treatment trials that include patients with atypical phenotypes of AD.
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Study details
- Effect size7.4%
- Evidence strengthModerate
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36001141) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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