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Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients
Pichet Binette A, Palmqvist S, Bali D, Farrar G, Buckley CJ, Wolk DA, Zetterberg H, Blennow K et al.. Alzheimer's research & therapy, 2022-03-29
Topic: Plasma and spinal-fluid biomarkers
Background Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer's disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). Methods We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Results Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75-0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82-0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79-0.95, p = 0.07). Conclusion We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD. Trial registration NCT01028053 , registered December 9, 2009.
Key findings
- Results Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75-0.93).
- Conclusion We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD.
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Study details
- Participants110
- Effect sizeAUC 0.84; AUC 0.89
- Evidence strengthLow
How this study scored 76/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for 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 and multi-centre collaboration, so those were left out: it earned 44 of the 58 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 2 / 4 | 110 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) |
| 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 35351181) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 44 of the 58 points we could judge it on is 76 out of 100. |
| Total | 76 / 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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Pichet Binette, A., Palmqvist, S., Bali, D., Farrar, G., Buckley, C. J., Wolk, D. A., et al. (2022). Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-022-00990-0
Vancouver
Pichet Binette A, Palmqvist S, Bali D, Farrar G, Buckley CJ, Wolk DA, et al. Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients. Alzheimer's research & therapy. 2022. doi:10.1186/s13195-022-00990-0. PMID: 35351181.
BibTeX
@article{pichetbinette2022-35351181,
author = {Pichet Binette, A. and Palmqvist, S. and Bali, D. and Farrar, G. and Buckley, C. J. and Wolk, D. A. and Zetterberg, H. and Blennow, K. and others},
title = {{Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer's dementia in mild cognitive impairment patients}},
journal = {Alzheimer's research \& therapy},
year = {2022},
doi = {10.1186/s13195-022-00990-0},
pmid = {35351181},
url = {https://doi.org/10.1186/s13195-022-00990-0}
}
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