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Comparative Analysis of Different Definitions of Amyloid-β Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer
Milà-Alomà M, Salvadó G, Shekari M, Grau-Rivera O, Sala-Vila A, Sánchez-Benavides G, Arenaza-Urquijo EM, González-de-Echávarri JM et al.. The journal of prevention of Alzheimer's disease, 2021-01-01
Topic: Amyloid, tau and blood-test diagnosis
Amyloid-β (Aβ) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early Aβ pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer's continuum is critical. Here, we compare different Aβ classification approaches and we show their performance in detecting pathophysiological changes downstream Aβ pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer's continuum. Participants underwent Aβ PET and CSF biomarkers assessment. We classified participants as Aβ -positive using five approaches: (1) CSF Aβ42 < 1098 pg/ml; (2) CSF Aβ42/40 < 0.071; (3) Aβ PET Centiloid > 12; (4) Aβ PET Centiloid > 30 or (5) Aβ PET Positive visual read. We assessed the correlations between Aβ biomarkers and compared the prevalence of Aβ positivity. We determined which approach significantly detected associations between Aβ pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher Aβ-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF Aβ-positive but PET Aβ-negative than CSF Aβ-negative but PET Aβ-positive. The CSF Aβ 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the Aβ-positive group. Altogether, we highlight the need for sensitive Aβ -classifications to study the preclinical Alzheimer's continuum. Approaches that define Aβ positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.
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APA 7th
Milà-Alomà, M., Salvadó, G., Shekari, M., Grau-Rivera, O., Sala-Vila, A., Sánchez-Benavides, G., et al. (2021). Comparative Analysis of Different Definitions of Amyloid-β Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer. The journal of prevention of Alzheimer's disease. https://doi.org/10.14283/jpad.2020.51
Vancouver
Milà-Alomà M, Salvadó G, Shekari M, Grau-Rivera O, Sala-Vila A, Sánchez-Benavides G, et al. Comparative Analysis of Different Definitions of Amyloid-β Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer. The journal of prevention of Alzheimer's disease. 2021. doi:10.14283/jpad.2020.51. PMID: 33336227.
BibTeX
@article{milaaloma2021-33336227,
author = {Milà-Alomà, M. and Salvadó, G. and Shekari, M. and Grau-Rivera, O. and Sala-Vila, A. and Sánchez-Benavides, G. and Arenaza-Urquijo, E. M. and González-de-Echávarri, J. M. and others},
title = {{Comparative Analysis of Different Definitions of Amyloid-β Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2021},
doi = {10.14283/jpad.2020.51},
pmid = {33336227},
url = {https://doi.org/10.14283/jpad.2020.51}
}
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Key findings
- We determined which approach significantly detected associations between Aβ pathology and tau/neurodegeneration CSF biomarkers.
- We found that CSF-based approaches result in a higher Aβ-positive prevalence than PET-based ones.
- The CSF Aβ 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the Aβ-positive group.
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Study details
- Participants368
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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 and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| 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 | 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 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 368 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 | — / 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 33336227) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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