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Population-based blood screening for pre-clinical Alzheimer’s disease: a British birth cohort at age 70
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero‐Rodriguez, Nicholas James Ashton, Jennifer M. Nicholas, David M. Cash, William Coath et al.. Journal of Neurology Neurosurgery & Psychiatry, 2022-05-27
Topic: Plasma and spinal-fluid biomarkers
In pre-clinical Alzheimer’s disease, cerebral amyloid-β (Aβ) deposition precedes symptoms; Aβ-targeted therapies may have maximum benefits at this stage. Existing Aβ status measurement techniques, including amyloid PET and CSF testing, are difficult to upscale. We therefore compared the concordance of three different blood-based techniques (liquid chromatography-mass spectrometry (LC¬-MS) measures of plasma Aβ, and single molecule array (Simoa) measures of plasma Aβ and phospho-tau181 (p-tau181)) with amyloid PET-positivity in dementia-free members of Insight 46, a sub-study of the British 1946 birth cohort. Of 441 dementia-free individuals with complete data, 82 (18.6%) were amyloid PET-positive. The area under the receiver operating characteristics curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628–0.762). The best perform- ing Simoa biomarker was p-tau181 (0.707; 0.646–0.768). LC-MS Aβ1–42/1–40 performed significantly better (0.817; 0.770–0.864), with a Youden’s index cut-point of 0.095 detecting amyloid PET-positivity with 86.6% sensitivity and 71.9% specificity. Without screening, 543 individuals would need PET scans, to obtain 100 PET-positive individuals. Screening using the base model would require 940 individuals, with 266 proceeding to scan. Using LC-MS Aβ1–42/1–40 alone would reduce these numbers to 623 and 243 respectively. Across a theoretical range of amyloid PET-positivity prevalence of 10–50%, LC-MS Aβ1–42/1–40 would consistently reduce scan numbers, with greater cost savings at lower prevalence. ashvini.keshavan@nhs.net
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APA 7th
Keshavan, A., Pannee, J., Karikari, T. K., Lantero‐Rodriguez, J., Ashton, N. J., Nicholas, J. M., et al. (2022). Population-based blood screening for pre-clinical Alzheimer’s disease: a British birth cohort at age 70. Journal of Neurology Neurosurgery & Psychiatry. https://doi.org/10.1136/jnnp-2022-abn.297
Vancouver
Keshavan A, Pannee J, Karikari TK, Lantero‐Rodriguez J, Ashton NJ, Nicholas JM, et al. Population-based blood screening for pre-clinical Alzheimer’s disease: a British birth cohort at age 70. Journal of Neurology Neurosurgery & Psychiatry. 2022. doi:10.1136/jnnp-2022-abn.297.
BibTeX
@article{keshavan2022-ab059739,
author = {Keshavan, Ashvini and Pannee, Josef and Karikari, Thomas K. and Lantero‐Rodriguez, Juan and Ashton, Nicholas James and Nicholas, Jennifer M. and Cash, David M. and Coath, William and others},
title = {{Population-based blood screening for pre-clinical Alzheimer’s disease: a British birth cohort at age 70}},
journal = {Journal of Neurology Neurosurgery \& Psychiatry},
year = {2022},
doi = {10.1136/jnnp-2022-abn.297},
url = {https://doi.org/10.1136/jnnp-2022-abn.297}
}
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Key findings
- LC-MS Aβ1–42/1–40 performed significantly better (0.817; 0.770–0.864), with a Youden’s index cut-point of 0.095 detecting amyloid PET-positivity with 86.6% sensitivity and 71.9% specificity.
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Study details
- Participants543
- Effect size18.6%; 86.6%; 71.9%
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design 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 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurology Neurosurgery & Psychiatry) |
| 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 | 2 / 4 | 543 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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