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Distinguishing Frontotemporal Lobar Degeneration Tau From TDP-43 Using Plasma Biomarkers
Katheryn A Q Cousins, Leslie M Shaw, Alice Chen-Plotkin, David A Wolk, Vivianna M Van Deerlin, Edward B Lee, Corey T McMillan, Murray Grossman et al.. JAMA neurology, 2022-11-01
Topic: Plasma and spinal-fluid biomarkers
Of 349 participants with available plasma data, 234 met inclusion criteria (31 controls, 141 in the training sample, and 62 in the validation sample). In the training sample, patients with FTLD-tau were older than patients with FTLD-TDP (FTLD-tau: n = 46; mean [SD] age, 65.8 [8.29] years; FTLD-TDP: n = 95; mean [SD] age, 62.3 [7.82] years; t84.6 = 2.45; mean difference, 3.57; 95% CI, 0.67-6.48; P = .02) but with similar sex distribution (FTLD-tau: 27 of 46 [59%] were male; FTLD-TDP: 51 of 95 [54%] were male; χ21 = 0.14; P = .70). In the validation sample, patients with PSPS-tau were older than those with ALS-TDP (PSPS-tau: n = 31; mean [SD] age, 69.3 [7.35] years; ALS-TDP: n = 31; mean [SD] age, 54.6 [10.17] years; t54.6 = 6.53; mean difference, 14.71; 95% CI, 10.19-19.23; P < .001) and had fewer patients who were male (PSPS-tau: 9 of 31 [29%] were male; ALS-TDP: 22 of 31 [71%] were male; χ21 = 9.3; P = .002). ROC revealed excellent discrimination of FTLD-tau from FTLD-TDP by plasma GFAP/NfL ratio (AUC = 0.89; 90% CI, 0.82-0.95; sensitivity = 0.73; 90% CI, 0.65-0.89; specificity = 0.89; 90% CI, 0.78-0.98), which was higher than either GFAP level alone (AUC = 0.65; 90% CI, 0.54-0.76) or NfL levels alone (AUC = 0.75; 90% CI, 0.64-0.85). In the validation sample, there was sensitivity of 0.84 (90% CI, 0.66-0.94) and specificity of 0.81 (90% CI, 0.62-0.91) when applying the autopsy-derived plasma GFAP/NfL threshold. CONCLUSIONS AND RELEVANCE: The plasma ratio of GFAP/NfL may discriminate FTLD-tau from FTLD-TDP.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cousins, K. A. Q., Shaw, L. M., Chen-Plotkin, A., Wolk, D. A., Van Deerlin, V. M., Lee, E. B., et al. (2022). Distinguishing Frontotemporal Lobar Degeneration Tau From TDP-43 Using Plasma Biomarkers. JAMA neurology. https://doi.org/10.1001/jamaneurol.2022.3265
Vancouver
Cousins KAQ, Shaw LM, Chen-Plotkin A, Wolk DA, Van Deerlin VM, Lee EB, et al. Distinguishing Frontotemporal Lobar Degeneration Tau From TDP-43 Using Plasma Biomarkers. JAMA neurology. 2022. doi:10.1001/jamaneurol.2022.3265. PMID: 36215050.
BibTeX
@article{cousins2022-36215050,
author = {Cousins, Katheryn A Q and Shaw, Leslie M and Chen-Plotkin, Alice and Wolk, David A and Van Deerlin, Vivianna M and Lee, Edward B and McMillan, Corey T and Grossman, Murray and others},
title = {{Distinguishing Frontotemporal Lobar Degeneration Tau From TDP-43 Using Plasma Biomarkers}},
journal = {JAMA neurology},
year = {2022},
doi = {10.1001/jamaneurol.2022.3265},
pmid = {36215050},
url = {https://doi.org/10.1001/jamaneurol.2022.3265}
}
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Key findings
- Of 349 participants with available plasma data, 234 met inclusion criteria (31 controls, 141 in the training sample, and 62 in the validation sample).
- In the training sample, patients with FTLD-tau were older than patients with FTLD-TDP (FTLD-tau: n = 46; mean [SD] age, 65.8 [8.29] years; FTLD-TDP: n = 95; mean [SD] age, 62.3 [7.82] years; t84.6 = 2.45; mean difference, 3.57; 95% CI, 0.67-6.48; P = .02) but with similar sex distribution (FTLD-tau: 27 of 46 [59%] were male; FTLD-TDP: 51 of 95 [54%] were male; χ21 = 0.14; P = .70).
- In the validation sample, patients with PSPS-tau were older than those with ALS-TDP (PSPS-tau: n = 31; mean [SD] age, 69.3 [7.35] years; ALS-TDP: n = 31; mean [SD] age, 54.6 [10.17] years; t54.6 = 6.53; mean difference, 14.71; 95% CI, 10.19-19.23; P < .001) and had fewer patients who were male (PSPS-tau: 9 of 31 [29%] were male; ALS-TDP: 22 of 31 [71%] were male; χ21 = 9.3; P = .002).
- ROC revealed excellent discrimination of FTLD-tau from FTLD-TDP by plasma GFAP/NfL ratio (AUC = 0.89; 90% CI, 0.82-0.95; sensitivity = 0.73; 90% CI, 0.65-0.89; specificity = 0.89; 90% CI, 0.78-0.98), which was higher than either GFAP level alone (AUC = 0.65; 90% CI, 0.54-0.76) or NfL levels alone (AUC = 0.75; 90% CI, 0.64-0.85).
- In the validation sample, there was sensitivity of 0.84 (90% CI, 0.66-0.94) and specificity of 0.81 (90% CI, 0.62-0.91) when applying the autopsy-derived plasma GFAP/NfL threshold.
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Study details
- Study designcross-sectional
- Participants46
- Effect sizeAUC = 0.89; AUC = 0.65; AUC = 0.75
- Evidence strengthLow
How this study scored 64/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomized / 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, multicenter collaboration and free to read, so those were left out: it earned 36 of the 56 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 46 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36215050) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 36 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 36 of the 56 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
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